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Purpose: Antihyperglycemic drug artemisinin (Art) has recently gained attention as a potential anticancer treatment. In this study, the poly(lactic-co-glycolic acid) (PLGA) polymer was used to create Art-containing nanofibers (NFs) using the electrospinning technique. Methods: The morphological characteristics, rate of degradation, and drug release profile of the NFs were described. In addition, we examined both the cytotoxic effects and internalization of reactive oxygen species (ROS), as well as the expression levels of apoptotic genes following the treatment of SK-BR-3 breast cancer cells with Art and Art-loaded PLGA nanofibers. Results: The bead-free, smooth surface, and randomly aligned electrospun NFs released the medication quickly at first and then steadily for more than 2 weeks. They also showed a rather steady rate of deterioration over the course of 24 days. After 48h, SK-BR-3 cells exposed to ART-loaded NFs shown a substantial cytotoxicity compared to free Art. Additionally, Art-loaded NFs effectively increased intracellular ROS levels, inducing death in cancer cells. Gene expression studies further demonstrated the ability of the produced Art-loaded NFs to significantly modify Bax and Bcl-2 levels as well as activate caspases-3 and P53 compared to free Art. Conclusion: Overall, the results demonstrated the Art-loaded PLGA nanofibers anticancer effectiveness, indicating that it may be employed as an implantable drug delivery system to decrease breast cancer recurrence following surgical resection. [ABSTRACT FROM AUTHOR]

AbstractErlotinib, a potent epidermal growth factor receptor (EGFR) inhibitor, faces bioavailability challenges due to poor water solubility and stability. This study aims to optimize erlotinib-loaded PLGA nanoparticles using a 32 factorial design to enhance drug delivery and therapeutic efficacy. The effects of PLGA concentration (R1) and NaTPP concentration (R2) on nanoparticle characteristics, including particle size, zeta potential, and polydispersity index (PDI), were investigated. The optimal formulation (F5) was identified and characterized, showing a particle size of 169.1 nm, a zeta potential of 20.0 mV, and a PDI of 0.146, indicating uniform and stable nanoparticles. Transmission electron microscopy (TEM) confirmed spherical nanoparticles with minimal aggregation, while X-ray diffraction (XRD) indicated an amorphous state of erlotinib. Formulation F5 demonstrated an entrapment efficiency of 81.9% and a yield of 83.0%. In-vitro drug release studies revealed a sustained release pattern with 90.0% cumulative release at 48 h, following Zero Order kinetics. Cytotoxicity assays showed low cytotoxicity across various cell lines. Statistical analysis confirmed the significant impact of formulation variables on nanoparticle properties. The systematic optimization of erlotinib-loaded nanoparticles has successfully identified formulation F5 as an optimal candidate with favorable characteristics, including minimal particle size, high stability, controlled drug release, and a safe cytotoxicity profile. Notably, the optimized formulation (F5) enhances therapeutic efficacy through improved bioavailability and targeted delivery, addressing the limitations of conventional therapies. These findings suggest that the optimized erlotinib-loaded nanoparticles hold significant potential for enhanced drug delivery and therapeutic efficacy. [ABSTRACT FROM AUTHOR]

The current strategy for treating osteomyelitis includes surgical procedures for complete debridement of the formed biofilm and necrotic tissues, systemic and oral antibiotic therapy, and the clinical use of cements and three-dimensional scaffolds as bone defect fillers and delivery systems for therapeutic agents. The aim of our research was to formulate a low-cost hybrid nanoparticulate biomaterial using poly(lactic-co-glycolic acid) (PLGA), in which we incorporated the therapeutic agent (ciprofloxacin), and to deposit this material on titanium plates using the matrix-assisted pulsed laser evaporation (MAPLE) technique. The deposited material demonstrated antibacterial properties, with all analyzed samples inhibiting the growth of tested bacterial strains, confirming the release of active substances from the investigated biocomposite. The poly(lactic-co-glycolic acid)-ciprofloxacin (PLGA-CIP) nanoparticle scaffolds displayed a prolonged local sustained release profile over a period of 45 days, which shows great promise in bone infections. Furthermore, the burst release ensures a highly efficient concentration, followed by a constant sustained release which allows the drug to remain in the implant-adjacent area for an extended time period. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disorder that affects millions of individuals globally. It is characterized by the loss of dopaminergic neurons in Substantia Nigra pars compacta (SNc) and striatum. Neuroimaging techniques such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance imaging (MRI) help diagnosing PD. In this study, the focus was on developing technetium-99 m ([99mTc]Tc) radiolabeled drug delivery systems using plant-derived compounds for the diagnosis of PD. Madecassoside (MA), a plant-derived compound, was conjugated with Levodopa (L-DOPA) to form MA-L-DOPA, which was then encapsulated using Poly Lactic-co-Glycolic Acid (PLGA) to create MA-PLGA and MA-L-DOPA-PLGA nanocapsules. Extensive structural analysis was performed using various methods such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), liquid chromatography–mass spectrometry (LC–MS), thin layer chromatography (TLC), high performance liquid chromatography (HPLC), dynamic light scattering (DLS), and scanning electron microscopy (SEM) to characterize the synthesized products. Radiochemical yields of radiolabeled compounds were determined using thin layer radio chromatography (TLRC) and high performance liquid radio chromatography (HPLRC) methods. In vitro cell culture studies were conducted on human neuroblastoma (SH-SY5Y) and rat pheochromocytoma (PC-12) cell lines to assess the incorporation of [99mTc]Tc radiolabeled compounds ([99mTc]Tc-MA, [99mTc]Tc-MA-L-DOPA, [99mTc]Tc-MA-PLGA and [99mTc]Tc-MA-L-DOPA-PLGA) and the cytotoxicity of inactive compounds (MA and MA-L-DOPA compounds and encapsulated compounds (MA-PLGA and MA-L-DOPA-PLGA). Additionally, the biodistribution studies were carried out on healthy male Sprague–Dawley rats and a Parkinson's disease experimental model to evaluate the compounds' bioactivity using the radiolabeled compounds. The radiochemical yields of all radiolabeled compounds except [99mTc]Tc-L-DOPA-PLGA were above 95% and had stability over 6 h. The cytotoxic effects of all substances on SH-SY5Y and PC-12 cells increase with increasing concentration values. The uptake values of PLGA-encapsulated compounds are statistically significant in SH-SY5Y and PC-12 cells. The biodistribution studies showed that [99mTc]Tc-MA is predominantly retained in specific organs and brain regions, with notable uptake in the prostate, muscle, and midbrain. PLGA-encapsulation led to higher uptake in certain organs, suggesting its biodegradable nature may enhance tissue retention, and surface modifications might further optimize brain penetration. Overall, the results indicate that radiolabeled plant-derived encapsulated drug delivery systems with [99mTc]Tc hold potential as diagnostic agents for PD symptoms. This study contributes to the advancement of drug delivery agents in the field of brain research. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii (T. gondii) is a zoonotic disease that poses great harm to humans and animals. So far, no effective T. gondii vaccine has been developed to provide fully protection against such parasites. Recently, numerous researches have focused on the use of poly-lactic-co-glycolic acid (PLGA) and chitosan (CS) for the vaccines against T. gondii infections. In this study, we employed PLGA and CS as the vehicles for T. gondii ribosome protein (TgRPS2) delivery. TgRPS2- PLGA and TgRPS2-CS nanospheres were synthesized by double emulsion solvent evaporation and ionic gelation technique as the nano vaccines. Before immunization in animals, the release efficacy and toxicity of the synthesized nanospheres were evaluated in vitro. Then, ICR mice were immunized intramuscularly, and immune protections of the synthesized nanospheres were assessed. The results showed that TgRPS2-PLGA and TgRPS2-CS nanospheres could induce higher levels of IgG and cytokines, activate dendritic cells, and promote the expression of histocompatibility complexes. The splenic lymphocyte proliferation and the enhancement in the proportion of CD4+ and CD8+ T lymphocytes were also observed in immunized animals. In addition, two types of nanospheres could significantly inhabit the replications of T. gondii in cardiac muscles and spleen tissues. All these obtained results in this study demonstrated that the TgRPS2 protein delivered by PLGA or CS nanospheres provided satisfactory immunoprotective effects in resisting T. gondii, and such formulations illustrated potential as prospective preventive agents for toxoplasmosis. [ABSTRACT FROM AUTHOR]

AbstractThis work focused on improving antimalarial therapy through the development and characterization of Atovaquone-Proguanil-loaded nanoparticles employing a 32 factorial design. The nanoparticles were prepared from combinations of Poly(lactic-co-glycolic acid) (PLGA) and Eudragit L100 polymers and different concentrations of PVA (polyvinyl alcohol). Based on the results obtained the formulations were characterized for the particle size, zeta potential, encapsulation efficiency, and percent drug release. Among the nine formulations, F5 proved to be the most favorable in the biophysical parameters with a particle size of 176.3 nm, a zeta potential of −33.5 mV, and an encapsulation efficiency of 86% was found in the present investigation. Experimental dissolution profile analysis indicated that F5 had a slow and controlled-release profile where approximately 92.5%. Besides, cytotoxicity studies employing MTT, LDH (lactate dehydrogenase), and Trypan blue reduction test also supported the biocompatibility of nanoparticles and F5 had the highest cell viability (96%) with the least LDH release of 4%. In stability studies conducted for six months, F5 was found to remain stable regarding physicochemical characteristics and drug release profile at different temperature conditions such as room temperature, 4 °C, and 45 °C. The use of folic acid-functionalized nanoparticles is more effective, according to parasitemia, survival rate, and weight loss in mice treated with the nanoparticles. This is because functionalized nanoparticles could be used to enhance anti-malarial therapies. [ABSTRACT FROM AUTHOR]

The basic purpose of this work was to develop environmentally friendly, biodegradable, and biocompatible polymeric nanoparticles of sorafenib that can effectively release the desired drug in a customized and controlled manner for targeting hepatocellular carcinoma. The solvent evaporation technique was employed for the synthesis of sorafenib-loaded PLGA-chitosan nanoparticles, followed by various experimental specifications and compatibility studies using poloxamer 407 as the stabilizer. The best nanoparticles thus synthesized were selected to be used for cytotoxicity investigations through in vitro and in vivo assessments. For the in vitro drug release tests, the dialysis bag diffusion technique was used. For both chitosan nanoparticles and PLGA loaded with sorafenib, a biphasic release pattern was found, exhibiting a protracted release lasting 10 days after a 24-h burst release. As experimental animals, rabbits were utilized to evaluate different in vivo pharmacokinetic properties of the selected formulations. Plasma samples were extracted with acetonitrile and analyzed through the developed HPLC method. Pharmacokinetic parameters such as AUC0-t, Cmax MRT, Vd, and half-life (t1/2) were enhanced significantly (p = 0.001), while clearance was considerably decreased (p = 0.001) for the chosen synthesized nanoparticles in contrast to the commercially accessible sorafenib formulation (Nexavar®). The cytotoxicity of the reference drug and sorafenibloaded PLGA and chitosan nanoparticles was calculated by performing an MTT assay against HepG2 cell lines. The developed polymeric sorafenib nanoformulations possess the appropriate physicochemical properties, better targeting, surface morphology, and prolonged release kinetics. The pharmacokinetic parameters were improved significantly when the results were compared with commercially available sorafenib formulations. [ABSTRACT FROM AUTHOR]

Salmonid rickettsial septicemia (SRS), caused by Piscirickettsia salmonis, has been the most severe health concern for the Chilean salmon industry. The efforts to control P. salmonis infections have focused on using antibiotics and vaccines. However, infected salmonids exhibit limited responses to the treatments. Here, we developed a poly (D, L-lactide-glycolic acid) (PLGA)-nanosystem functionalized with Atlantic salmon IgM (PLGA-IgM) to specifically deliver florfenicol into infected cells. Polymeric nanoparticles (NPs) were prepared via the double emulsion solvent-evaporation method in the presence of florfenicol. Later, the PLGA-NPs were functionalized with Atlantic salmon IgM through carbodiimide chemistry. The nanosystem showed an average size of ~380–410 nm and a negative surface charge. Further, florfenicol encapsulation efficiency was close to 10%. We evaluated the internalization of the nanosystem and its impact on bacterial load in SHK-1 cells by using confocal microscopy and qPCR. The results suggest that stimulation with the nanosystem elicits a decrease in the bacterial load of P. salmonis when it infects Atlantic salmon macrophages. Overall, the IgM-functionalized PLGA-based nanosystem represents an alternative to the administration of antibiotics in salmon farming, complementing the delivery of antibiotics with the stimulation of the immune response of infected macrophages. [ABSTRACT FROM AUTHOR]

Burn wounds are associated with infections, drug resistance, allergic reactions, odour, bleeding, excess exudates, and scars, requiring prolonged hospital stay. It is crucial to develop wound dressings that can effectively combat allergic reactions and drug resistance, inhibit infections, and absorb excess exudates to accelerate wound healing. To overcome the above-mentioned problems associated with burn wounds, SA/PVA/PLGA/Capparis sepiaria and SA/PVA/Capparis sepiaria nanofibers incorporated with Capparis sepiaria plant extract were prepared using an electrospinning technique. Fourier-transform infrared spectroscopy confirmed the successful incorporation of the extract into the nanofibers without any interaction between the extract and the polymers. The nanofibers displayed porous morphology and a rough surface suitable for cellular adhesion and proliferation. SA/PVA/PLGA/Capparis sepiaria and SA/PVA/Capparis sepiaria nanofibers demonstrated significant antibacterial effects against wound infection-associated bacterial strains: Pseudomonas aeruginosa, Enterococcus faecalis, Mycobaterium smegmatis, Escherichia coli, Enterobacter cloacae, Proteus vulgaris, and Staphylococcus aureus. Cytocompatibility studies using HaCaT cells revealed the non-toxicity of the nanofibers. SA/PVA/PLGA/Capparis sepiaria and SA/PVA/Capparis sepiaria nanofibers exhibited hemostatic properties, resulting from the synergistic effect of the plant extract and polymers. The in vitro scratch wound healing assay showed that the SA/PVA/Capparis sepiaria nanofiber wound-healing capability is more than the plant extract and a commercially available wound dressing. The wound-healing potential of SA/PVA/Capparis sepiaria nanofiber is attributed to the synergistic effect of the phytochemicals present in the extract, their porosity, and the ECM-mimicking structure of the nanofibers. The findings suggest that the electrospun nanofibers loaded with Capparis sepiaria extract are promising wound dressings that should be explored for burn wounds. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii (T. gondii) is a zoonotic disease that poses great harm to humans and animals. So far, no effective T. gondii vaccine has been developed to provide fully protection against such parasites. Recently, numerous researches have focused on the use of poly-lactic-co-glycolic acid (PLGA) and chitosan (CS) for the vaccines against T. gondii infections. In this study, we employed PLGA and CS as the vehicles for T. gondii ribosome protein (TgRPS2) delivery. TgRPS2- PLGA and TgRPS2-CS nanospheres were synthesized by double emulsion solvent evaporation and ionic gelation technique as the nano vaccines. Before immunization in animals, the release efficacy and toxicity of the synthesized nanospheres were evaluated in vitro. Then, ICR mice were immunized intramuscularly, and immune protections of the synthesized nanospheres were assessed. The results showed that TgRPS2-PLGA and TgRPS2-CS nanospheres could induce higher levels of IgG and cytokines, activate dendritic cells, and promote the expression of histocompatibility complexes. The splenic lymphocyte proliferation and the enhancement in the proportion of CD4+ and CD8+ T lymphocytes were also observed in immunized animals. In addition, two types of nanospheres could significantly inhabit the replications of T. gondii in cardiac muscles and spleen tissues. All these obtained results in this study demonstrated that the TgRPS2 protein delivered by PLGA or CS nanospheres provided satisfactory immunoprotective effects in resisting T. gondii, and such formulations illustrated potential as prospective preventive agents for toxoplasmosis. [ABSTRACT FROM AUTHOR]

The post COVID-19 pandemic era has emerged with more efficient vaccines, all based on genetic materials. However, to expand the use of nucleic components as vaccines, a new generation of nanosystems particularly constructed to increase RNA/DNA stability, half-life and facilitate administration are still required. This review highlights novel developments in mRNA and pDNA vaccines formulated into nanostructures exclusively composed by biopolymeric materials. Recent advances suggest that a new generation of vaccines may arise by adapting the structural features of biopolymers with the effectiveness of nucleic acids. The advantages offered by biopolymers, such as increased stability and targeting ability may cause a revolution in the immunization field for offering promptly adaptable and effective formulations for worldwide distribution. Graphical Abstract Article highlights Polymeric biomaterials for nucleic acid delivery in vaccines We review the potential of chitosan, PLL, PEI, PLA and PLGA as mRNA/DNA vaccine systems. Chitosan Chitosan has significant potential for new intranasal vaccine designs. Poly(L-lysine) Vaccines based on PLL still require long, difficult and costly biomaterial modifications for translation. Poly(ethyleneimine) PEI's cytotoxicity may be circumvented by reducing the molar mass and using shorter chains. Poly(lactic acid) & poly(lactide-co-glycolide) PLA or PLGA lack chemical functionalities for optimal nuclei acid anchoring. Conclusion & future perspectives The cationic character causes a balance between nuclei material deliver efficiency and cytotoxicity. [ABSTRACT FROM AUTHOR]

The present study is designed to evaluate the nanotherapeutic efficacy of prepared PLGA‐loaded Nedaplatin (PLGA‐NDP) against 7,12‐dimethyl benz(a)anthracene (DMBA)‐induced experimental oral carcinogenesis in hamster buccal pouch (HBP) model. The buccal pouch of golden Syrian hamsters was painted with 0.5% DMBA in liquid paraffin three times a week for 14 weeks, ultimately leading to the development of oral squamous cell carcinoma (OSCC). Oral administration of PLGA‐NDP (preinitiation) and Cisplatin delivery (5 mg/kg b.wt) started 1 week before the carcinogen exposure and continued on alternative days. Post‐administration of PLGA‐NDP (5 mg/kg b.wt) started 2 days after carcinogen (DMBA) induction until the end of the experiment. After the 14th week, we observed that DMBA‐painted hamsters exhibited tumor formation, morphological alterations, and well‐differentiated OSSC in addition to the responsive molecular proteins during oral carcinogenesis. Furthermore, immunoblotting analysis demonstrated that PLGA‐NDP inhibits Notch signaling, as evidenced by downregulation of Bcl‐Xl, Bcl‐2, p21, PGE2, HGF, and CXCL12 proteins, and upregulation of p53 and Bax. This apoptotic response is crucial for PLGA‐NDP to induce apoptosis. In addition, RT‐PCR results showed that PLGA‐NDP nanoparticles play a downregulatory role in the therapeutic action of the notch signaling gene (Notch1, Notch 2, Hes1, Hey1, and Jagged1) at the mRNA transcription level in HBP carcinoma. Taken together, these data indicate that PLGA‐NDP is a potent inhibitor of oral carcinogenesis and the expansion of cells that specifically target the Notch signaling pathway indicates that obstructing Notch signaling could potentially serve as a new and innovative therapeutic approach for oral squamous cell carcinoma (OSCC). Summary: The present investigation assesses the therapeutic efficacy of PLGA‐loaded Nedaplatin (PLGA‐NDP) in treating oral cancer within a hamster model. The research highlights that PLGA‐NDP specifically targets the Notch signaling pathway and initiates apoptosis to impede oral carcinogenesis. To achieve this, we incorporate techniques such as histopathological examination, Western blot analysis, and quantitative mRNA expression analysis to visualize the presence of PLGA‐NDP nanoparticles within specific organs and tissues, evaluate their role in binding and uptake, and assess internalization and clearance. Our findings indicate that obstructing Notch signaling may represent a novel therapeutic strategy for oral squamous cell carcinoma (OSCC). [ABSTRACT FROM AUTHOR]

Capsicum annuum L. var. "Chile de árbol" combined with poly(lactic-co-glycolic acid) (PLGA) and TiO2-ZnO oxides synthesized at different molar ratios and pH (Ti-Zn A and B 3:1, 1:1, and 1:3) via the sol-gel method was characterized by the Brunauer–Emmett–Teller (BET) method, a UV-Vis spectrophotometer (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), High-Performance Liquid Chromatography (HPLC-DAD), and a release profile through mathematical models to explain its behavior. Furthermore, FTIR revealed the presence of PLGA, TiO2, and ZnO as well as amino group characteristics from oleoresin components, principally alkaloid groups (capsaicin and dihydrocapsaicin), as evidenced by HPLC, to identify the presence of capsaicin and dihydrocapsaicin. The UV-Vis spectra showed a slight hypsochromic shift in the PLGA treatments. The release profile demonstrated a higher controllable release in the PLGA treatments than in the double nanoemulsions. Moreover, it is important to note that the effect of NPs influenced the release profile itself, increasing the release when NPs were synthesized at an acidic pH. Therefore, the TiZnOl/PLGA A characteristics suggest that these results have potential for pharmaceutical (as drug carriers) and medical applications. [ABSTRACT FROM AUTHOR]

Swine Glasser's disease, instigated by Haemophilus parasuis (H. parasuis), is a significant bacterial infection that causes substantial economic losses in pig farming operations. The role of mucosal immunity is pivotal in defending against H. parasuis. This study focused on the construction of PLGA microspheres that encapsulate the outer membrane protein OMP16 from H. parasuis (PLGA-OMP16) and evaluated their immunological effectiveness in a mouse model. After being intranasally immunized twice, the PLGA-OMP16 microspheres effectively induced IgAs in saliva and nasal and lung fluids. The PLGA-OMP16 microspheres also significantly increased the number of anti H. parasuis IgGs in serum. Furthermore, the PLGA-OMP16 microspheres triggered elevated levels of IL-2, IL-4, and IFN-γ. The mice vaccinated with PLGA-OMP16 showed a significant reduction in H. parasuis burden in the spleen and lungs following bacterial challenge. These results indicate that intranasal immunization using PLGA microspheres is a promising adjuvant delivery system for vaccines targeting H. parasuis. [ABSTRACT FROM AUTHOR]

Melanoma is the main cause of death among skin cancers and its incidence worldwide has been experiencing an appalling increase. However, traditional treatments lack effectiveness in advanced or metastatic patients. Immunotherapy, meanwhile, has been shown to be an effective treatment option, but the rate of cancers responding remains far from ideal. Here we have developed a personalized neoantigen peptide-based cancer vaccine by encapsulating patient derived melanoma neoantigens in polyethylenimine (PEI)-functionalised poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and coating them with polyinosinic:polycytidylic acid (poly(I:C)). We found that PLGA NPs can be effectively modified to be coated with the immunoadjuvant poly(I:C), as well as to encapsulate neoantigens. In addition, we found that both dendritic cells (DCs) and lymphocytes were effectively stimulated. Moreover, the developed NP was found to have a better immune activation profile than NP without poly(I:C) or without antigen. Our results demonstrate that the developed vaccine has a high capacity to activate the immune system, efficiently maturing DCs to present the antigen of choice and promoting the activity of lymphocytes to exert their cytotoxic function. Therefore, the immune response generated is optimal and specific for the elimination of melanoma tumour cells. Created with BioRender.com [ABSTRACT FROM AUTHOR]

Oral Topiramate therapy is associated with systemic adverse effects including paresthesia,abdominal pain, and fluctuations in plasma levels. The purpose of this research was to develop an intranasal in situ gel based system comprising Topiramate polymeric nanoparticles and evaluate its potential both in vitro and in vivo. Poly (lactic-co-glycolic acid) (PLGA)nanoparticles prepared by nanoprecipitation method were added into the in situ gelling system of Poloxamer 407 and HPMC K4M. Selected formulation (TG5) was evaluated for physicochemical properties, nasal permeation and in vivo pharmacokinetics in rats. PLGAnanoparticles (O1) exhibited low particle size (~ 144.4 nm), good polydispersity index (0.202), negative zeta potential (-12.7 mV), and adequate entrapment efficiency (64.7%). Developed in situ gel showed ideal pH (6.5), good gelling time (35 s), gelling temperature(37℃), suitable viscosity (1335 cP)and drug content of 96.2%. In vitro drug release conformedto Higuchi release kinetics, exhibiting a biphasic pattern of initial burst release and sustained release for 24 h. Oral administration of the drug to Sprague–Dawley rats (G3) showed higher plasma Cmax(504 ng/ml, p < 0.0001) when compared to nasal delivery of in situ gel (G4) or solution (G5). Additionally, AUC0-α of G3 (8786.82 ng/ml*h) was considerably higher than othergroups. Brain uptake data indicates a higher drug level with G4 (112.47 ng /ml) at 12 h when compared to G3. Histopathological examination of groups; G1 (intranasal saline), G2(intranasal placebo), G3, G4, and G5 did not show any lesions of pathological significance. Overall, the experimental results observed were promising and substantiated the potential of developed in situ gel for intranasal delivery. [ABSTRACT FROM AUTHOR]

Background: Curcumin, a compound in turmeric, shows potential in cancer treatment but is hindered by low bioavailability and solubility. Nanocurcumin, enhanced through nanotechnology, addresses these limitations, offering potential in oncological applications. This review systematically examines the efficacy, bioavailability, and safety of nanocurcumin in cancer treatment, collating data from in vitro, in vivo, and clinical studies. Methods: A comprehensive systematic search was conducted across four major databases: PubMed (Medline), Scopus, Web of Science, and Embase (up to February 2024). The selection criteria were based on the PICOT structure, and studies were assessed for risk of bias using the Cochrane bias risk tool for clinical studies and related checklists for in vitro and in vivo studies. Statistical analyses were performed in STATA software version 17. Results: In total, 8403 articles were identified and assessed, and then only 61 articles were found eligible to be included. Nanocurcumin formulations, especially with Poly (lactic-co-glycolic acid) (PLGA), displayed superior solubility and therapeutic efficacy. In vitro studies highlighted its enhanced cellular uptake and anti-proliferative effects, particularly against cervical cancer cells. In vivo studies confirmed its chemopreventive efficacy and potential synergy with other cancer therapies. Though in early stages, clinical trials showed promise in reducing side effects and improving efficacy in cancer treatments. Conclusion: Nanocurcumin shows promise as an innovative approach in cancer therapy, potentially offering improved efficacy and reduced side effects compared to traditional treatments. Early clinical trials indicate its potential to enhance the quality of life for cancer patients by mitigating treatment-related toxicities and improving therapeutic outcomes. However, larger randomized controlled trials are necessary to definitively establish its clinical efficacy, optimal dosing regimens, and long-term safety profile across various cancer types. As research progresses, nanocurcumin could become a valuable addition to the oncologist's toolkit, particularly in combination therapies or for patients intolerant to conventional treatments. Future clinical studies should focus on optimizing treatment protocols, identifying responsive patient populations, and assessing long-term outcomes to facilitate the translation of these promising findings into standard clinical practice. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusion The lipid‐lowering simvastatin (SIM) has been shown to be an effective inhibitor of keloid proliferation. However, due to its low water solubility and short half‐life, simvastatin aggregates to the liver and does not reach the skin lesions after oral administration, which restricts its widespread clinical use. The development of nanomedicine provides the possibility for us to break through this bottleneck problem clinically. The objective of this study was to investigate the feasibility of using complex nanocontrolled delivery system (CNDS), simvastatin‐loaded polyethylene glycol‐poly lactic‐co‐glycolic acid (PEG‐PLGA), in the treatment of keloids.In the in vitro study, the release of simvastatin in fibroblasts by CNDS@Simvastatin and its effect on inhibition of the proliferation of fibroblasts, Col Ι, and CTGF by the slow release of simvastatin were assessed. The efficacy of CNDS@Simvastatin in improving keloids and the biocompatibility and safety of CNDS@Simvastatin were examined in vivo by establishing a murine ear keloid model.CNDS@Simvastatin showed sustained and uniform inhibition of the proliferation of fibroblasts, Col Ι, and CTGF via the gradual release of simvastatin over 72 h. It was efficient in the treatment of the murine ear keloid with no observable toxic side effects on various organs.Simvastatin‐loaded copolymer acid‐sensitive nanocarriers, CNDS@Simvastatin nanospheres, were successfully developed in this study, and these were characterized by favorable physicochemical properties and biocompatibility. [ABSTRACT FROM AUTHOR]

Poly(lactic-co-glycolic acid) (PLGA) is a widely used biodegradable and biocompatible copolymer in drug delivery systems (DDSs). In this article, we highlight the critical physicochemical properties of PLGA, including its molecular weight, intrinsic viscosity, monomer ratio, blockiness, and end caps, that significantly influence drug release profiles and degradation times. This review also covers the extensive literature on the application of PLGA in delivering small-molecule drugs, proteins, peptides, antibiotics, and antiviral drugs. Furthermore, we discuss the role of PLGA-based DDSs in the treating various diseases, including cancer, neurological disorders, pain, and inflammation. The incorporation of drugs into PLGA nanoparticles and microspheres has been shown to enhance their therapeutic efficacy, reduce toxicity, and improve patient compliance. Overall, PLGA-based DDSs holds great promise for the advancement of the treatment and management of multiple chronic conditions. [ABSTRACT FROM AUTHOR]

Background: Alveolar Bone loss occurs frequently during the first six months after tooth extraction. Various studies have proposed different methods to reduce as much as possible the atrophy of the alveolar ridge after tooth extraction. Filling the socket with biomaterials after extraction can reduce the resorption of the alveolar ridge. We compared the height of the alveolar process at the mesial and distal aspects of the extraction site and the resorption rate was calculated after the application of HA/β-TCP or synthetic co-polymer polyglycolic - polylactic acid PLGA mixed with blood to prevent socket resorption immediately and after tooth extraction. Methods: The study was conducted on 24 extraction sockets of impacted mandibular third molars bilaterally, vertically, and completely covered, with a thin bony layer. HA/β-TCP was inserted into 12 of the dental sockets immediately after extraction, and the synthetic polymer PLGA was inserted into 12 of the dental sockets. All sockets were covered completely with a full-thickness envelope flap. Follow-up was performed for one year after extraction, using radiographs and stents for the vertical alveolar ridge measurements. Results: The mean resorption rate in the HA/β-TCP and PLGA groups was ± 1.23 mm and ± 0.1 mm, respectively. A minimal alveolar bone height reduction of HA/β-TCP was observed after 9 months, the reduction showed a slight decrease to 0.93 mm, while this rate was 0.04 mm after 9 months in the PLGA group. Moreover, the bone height was maintained after three months, indicating a good HA/β-TCP graft performance in preserving alveolar bone (1.04 mm) while this rate was (0.04 mm) for PLGA. Conclusion: The PLGA graft demonstrated adequate safety and efficacy in dental socket preservation following tooth extraction. However, HA/β-TCP causes greater resorption at augmented sites than PLGA, which clinicians should consider during treatment planning. [ABSTRACT FROM AUTHOR]

Background: Functionalized nanoparticles (NPs) represent a cutting edge in innovative clinical approaches, allowing for the delivery of selected compounds with higher specificity in a wider time frame. They also hold promise for novel theranostic applications that integrate both diagnostic and therapeutic functions. Pathogens are continuously evolving to try to escape the strategies designed to treat them. Objectives: In this work, we describe the development of a biotechnological device, Nano-Immuno-Probes (NIPs), for early detection and infections treatment. Human Herpes Simplex Virus 2 was chosen as model pathogen. Methods: NIPs consist of PLGA-PEG-Sulfone polymeric NPs conjugated to recombinant Fab antibody fragments targeting the viral glycoprotein G2. NIPs synthesis involved multiple steps and was validated through several techniques. Results: DLS analysis indicated an expected size increase with a good polydispersity index. Z-average and z-potential values were measured for PLGA-PEG-Bis-Sulfone NPs (86.6 ± 10.9 nm; –0.7 ± 0.3 mV) and NIPs (151 ± 10.4 nm; −5.1 ± 1.9 mV). SPR assays confirmed NIPs' specificity for the glycoprotein G2, with an apparent KD of 1.03 ± 0.61 µM. NIPs exhibited no cytotoxic effects on VERO cells at 24 and 48 h. Conclusions: This in vitro study showed that NIPs effectively target HSV-2, suggesting the potential use of these nanodevices to deliver both contrast agents as well as therapeutic compounds. [ABSTRACT FROM AUTHOR]

Compared with oral or injection administration, percutaneous immunotherapy presents a promising treatment modality for food allergies, providing low invasiveness and safety. This study investigated the efficacy of percutaneous immunotherapy using hen egg lysozyme (HEL)-loaded PLGA-PEG-PLGA nanoparticles (NPs), as an antigen model protein derived from egg white, compared with that of HEL-loaded chitosan hydroxypropyltrimonium chloride (CS)-modified PLGA NPs used in previous research. The intradermal retention of HEL in excised mouse skin was measured using Franz cells, which revealed a 2.1-fold higher retention with PLGA-PEG-PLGA NPs than that with CS-modified PLGA NPs. Observation of skin penetration pathways using fluorescein-4-isothiocyanate (FITC)-labeled HEL demonstrated successful delivery of HEL deep into the hair follicles with PLGA-PEG-PLGA NPs. These findings suggest that after NPs delivery into the skin, PEG prevents protein adhesion and NPs aggregation, facilitating stable delivery deep into the skin. Subsequently, in vivo percutaneous administration experiments in mice, with concurrent iontophoresis, demonstrated a significant increase in serum IgG1 antibody production with PLGA-PEG-PLGA NPs compared with that with CS-PLGA NPs after eight weeks of administration. Furthermore, serum IgE production in each NP administration group significantly decreased compared with that by subcutaneous administration of HEL solution. These results suggest that the combination of PLGA-PEG-PLGA NPs and iontophoresis is an effective percutaneous immunotherapy for food allergies. [ABSTRACT FROM AUTHOR]

Methotrexate is a potent anticancer drug whose strong efflux is facilitated by the brain's efflux transporter. As an efflux transporter blocker, albumin increased the drug's concentration in the brain. Methotrexate-loaded nanoparticles were produced by evaporating the emulsification fluid. Improvements and analyses were made to the following aspects of the generated nanoparticles: size, polydispersity, zeta potential, entrapment efficiency, percentage yield, scanning electron microscopy, in vitro drug release studies, and sterilization. The particle size was determined to be in the nano range, and homogeneity of particle size was suggested by a low polydispersity index result. Particle diameters of 168 nm were observed in the F5 preparation, and zeta potential values of −1.5 mV suggested that the preparation produced adequate repulsive interactions between the nanoparticles. Albumin and dopamine HCl were employed to coat the methotrexate-loaded nanoparticles to guarantee that the brain received an adequate amount of them. The homogeneity of albumin coated nanoparticles was demonstrated by the low% PDI values of 0.129 and 0.122 for albumin coated nanoparticles (MNPs-Alb) and polymerized dopamine HCl and albumin coated nanoparticles (MNPs-PMD-Alb), respectively. After 48 h of incubation, the cell viability measured at the same drug concentration (5 mg) decreased for the F5, albumin coated nanoparticles, polymerized dopamine HCl coated nanoparticles, and polymerized dopamine HCl and albumin coated nanoparticles, respectively. Our primary findings demonstrate that the albumin nanoparticles containing methotrexate are designed to deliver the drug gradually. With minimal cytotoxicity, the intended preparation might give the brain an appropriate dosage of methotrexate. [ABSTRACT FROM AUTHOR]

Safranal, the main bioactive compound in saffron responsible for its desirable aroma, has been widely studied for its various biological potentials in both in vitro and in vivo conditions. In the present research, safranal was encapsulated in poly(lactic-co-glycolic acid) nanoparticles (SAF-PLGA-NPs) as an efficient carrier system and characterized using DLS, ZETA potential, SEM, TEM and FTIR methods. The study aimed to investigate the antioxidant potential and anticancer properties of SAF-PLGA-NPs against two distinct cell lines including normal human foreskin fibroblast (HFF) cells and pancreatic cancer (PANC) cells. The apoptotic gene profiling (Bax, Bcl2, and Caspase 8) was also analyzed to determine the mechanism of action of SAF-PLGA-NPs. The obtained results manifested that SAF-PLGA-NPs were synthesized into round particles measuring 229.19 nm. They were also found to be single-dispersed and stable, with a ζ-potential of − 20.87 mV. The nanoparticles showed strong cytotoxicity activity against PANC cells, with an IC50 value of 35.38 μg/mL compared to normal cells. Moreover, the SAF-PLGA-NPs significantly upregulated the expression of Bax and caspase 8 genes while down-regulating the expression of the Bcl2 gene in the PANC cell line, which is a promising mechanism for treating pancreatic cancer. Our funding suggests that SAF-PLGA-NPs could be a promising drug delivery system and provide a strong foundation for further research on SAF-PLGA-NPs as a potential treatment option for cancer. [ABSTRACT FROM AUTHOR]

Polymeric nanoparticles (NPs), specifically those comprised of biodegradable and biocompatible polyesters, have been heralded as a game‐changing drug delivery platform. In fact, poly(α‐hydroxy acids) such as polylactide (PLA), poly(lactide‐co‐glycolide) (PLGA), and poly(ε‐caprolactone) (PCL) have been heavily researched in the past three decades as the material basis of polymeric NPs for drug delivery applications. As materials, these polymers have found success in resorbable sutures, biodegradable implants, and even monolithic, biodegradable platforms for sustained release of therapeutics (e.g., proteins and small molecules) and diagnostics. Few fields have gained more attention in drug delivery through polymeric NPs than cancer therapy. However, the clinical translational of polymeric nanomedicines for treating solid tumors has not been congruent with the fervor or funding in this particular field of research. Here, we attempt to provide a comprehensive snapshot of polyester NPs in the context of chemotherapeutic delivery. This includes a preliminary exploration of the polymeric nanomedicine in the cancer research space. We examine the various processes for producing polyester NPs, including methods for surface‐functionalization, and related challenges. After a detailed overview of the multiple factors involved with the delivery of NPs to solid tumors, the crosstalk between particle design and interactions with biological systems is discussed. Finally, we report state‐of‐the‐art approaches toward effective delivery of NPs to tumors, aiming at identifying new research areas and re‐evaluating the reasons why some research avenues have underdelivered. We hope our effort will contribute to a better understanding of the gap to fill and delineate the future research work needed to bring polyester‐based NPs closer to clinical application. This article is categorized under:Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic DiseaseNanotechnology Approaches to Biology > Nanoscale Systems in BiologyTherapeutic Approaches and Drug Discovery > Emerging Technologies [ABSTRACT FROM AUTHOR]

Abstract Purpose Antihyperglycemic drug artemisinin (Art) has recently gained attention as a potential anticancer treatment. In this study, the poly(lactic-co-glycolic acid) (PLGA) polymer was used to create Art-containing nanofibers (NFs) using the electrospinning technique. Methods The morphological characteristics, rate of degradation, and drug release profile of the NFs were described. In addition, we examined both the cytotoxic effects and internalization of reactive oxygen species (ROS), as well as the expression levels of apoptotic genes following the treatment of SK-BR-3 breast cancer cells with Art and Art-loaded PLGA nanofibers. Results The bead-free, smooth surface, and randomly aligned electrospun NFs released the medication quickly at first and then steadily for more than 2 weeks. They also showed a rather steady rate of deterioration over the course of 24 days. After 48h, SK-BR-3 cells exposed to ART-loaded NFs shown a substantial cytotoxicity compared to free Art. Additionally, Art-loaded NFs effectively increased intracellular ROS levels, inducing death in cancer cells. Gene expression studies further demonstrated the ability of the produced Art-loaded NFs to significantly modify Bax and Bcl-2 levels as well as activate caspases-3 and P53 compared to free Art. Conclusion Overall, the results demonstrated the Art-loaded PLGA nanofibers anticancer effectiveness, indicating that it may be employed as an implantable drug delivery system to decrease breast cancer recurrence following surgical resection.

Compared with other drug loading methods, PLGA drug-loaded microspheres have the advantages of sustained and controlled release ability, biodegradability, drug release stability, and targeted delivery function, which have become a research hotspot in pharmaceutics. With the improvement of the preparation technology and the quality of microspheres, they have been gradually promoted in clinical practice, and have achieved remarkable results in the treatment of tumors, osteoarthritis, diabetes, eye diseases and so on. However, there is still a lack of systematic review on the application of PLGA microspheres in stomatology. This article aims to introduce the clinical application characteristics of PLGA microspheres, and review their application prospect in oral and maxillofacial tumors, temporomandibular joint diseases, periodontitis, caries and alveolar bone defects, so as to provide reference for their application in stomatology.

Abstract Background Curcumin, a compound in turmeric, shows potential in cancer treatment but is hindered by low bioavailability and solubility. Nanocurcumin, enhanced through nanotechnology, addresses these limitations, offering potential in oncological applications. This review systematically examines the efficacy, bioavailability, and safety of nanocurcumin in cancer treatment, collating data from in vitro, in vivo, and clinical studies. Methods A comprehensive systematic search was conducted across four major databases: PubMed (Medline), Scopus, Web of Science, and Embase (up to February 2024). The selection criteria were based on the PICOT structure, and studies were assessed for risk of bias using the Cochrane bias risk tool for clinical studies and related checklists for in vitro and in vivo studies. Statistical analyses were performed in STATA software version 17. Results In total, 8403 articles were identified and assessed, and then only 61 articles were found eligible to be included. Nanocurcumin formulations, especially with Poly (lactic-co-glycolic acid) (PLGA), displayed superior solubility and therapeutic efficacy. In vitro studies highlighted its enhanced cellular uptake and anti-proliferative effects, particularly against cervical cancer cells. In vivo studies confirmed its chemopreventive efficacy and potential synergy with other cancer therapies. Though in early stages, clinical trials showed promise in reducing side effects and improving efficacy in cancer treatments. Conclusion Nanocurcumin shows promise as an innovative approach in cancer therapy, potentially offering improved efficacy and reduced side effects compared to traditional treatments. Early clinical trials indicate its potential to enhance the quality of life for cancer patients by mitigating treatment-related toxicities and improving therapeutic outcomes. However, larger randomized controlled trials are necessary to definitively establish its clinical efficacy, optimal dosing regimens, and long-term safety profile across various cancer types. As research progresses, nanocurcumin could become a valuable addition to the oncologist's toolkit, particularly in combination therapies or for patients intolerant to conventional treatments. Future clinical studies should focus on optimizing treatment protocols, identifying responsive patient populations, and assessing long-term outcomes to facilitate the translation of these promising findings into standard clinical practice.

Objective: To study the effect of a nanoparticulate brain-derived neurotrophic factor with surfactant (BDNF) on the modeled depression not associated with stress in mice Methods: Thirty-six C57BL/6 mice weighing 20-25 g were included in the study with reserpine-induced depression. The animals were divided into three groups: Group 1 – negative control, involving animals treated with normal saline, Group 2 – positive control involving animals treated with a traditional antidepressant fluoxetine, and Group 3 – experimental, treated with nanoparticulate BDNF with a surfactant. Open field, sucrose preference, and forced swimming tests were applied in the study, and the ELISA method was used to determine the corticosterone level in the serum. Digital morphometry of the adrenal cortex and thymus was done. SPSS 27.0.1 software was used for statistics, with a p

Qian Cao,1,&ast; Ruijie Zhou,2,&ast; Songlin Guo,3 Kai Meng,4 Xiaojuan Yang,5 Miao Liu,1 Bin Ma,6 Chunxia Su,5 Xiangguo Duan2 1The First School of Clinical Medicine, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 2School of Inspection, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 3Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Yinchuan, 750004, People’s Republic of China; 4Traditional Chinese Medicine Hospital of Ningxia Medical University, Yinchuan, 750003, People’s Republic of China; 5School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 6Department of Oncology Surgery, the First People’s Hospital of Yinchuan, Yinchuan, 750004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunxia Su, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China, Email 1651085195@qq.com Xiangguo Duan, School of Inspection, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China, Email 2455281549@qq.comBackground: Tumor vaccines have achieved remarkable progress in treating patients with various tumors in clinical studies. Nevertheless, extensive research has also revealed that tumor vaccines are not up to expectations for the treatment of solid tumors due to their low immunogenicity. Therefore, there is an urgent need to design a tumor vaccine that can stimulate a broad anti-tumor immune response.Methods: In this work, we developed a nanovaccine (NP-TCL@APS), which includes nanoparticles loaded with colorectal cancer tumor cell lysates (TCL) and Astragalus polysaccharides (APS) into poly (lactic-co-glycolic acid) to induce a robust innate immune response. The NP-TCL@APS was identified by transmission electron microscopy and Malvern laser particle size analyzer. The killing and immune activation effects of NP-TCL@APS were evaluated in vitro. Finally, safety and anti-tumor efficacy were evaluated in the colorectal cancer tumor-bearing mouse model.Results: We found that NP-TCL@APS was preferentially uptaken by DC and further promoted the activation of DC in vitro. Additionally, nanoparticles codelivery of TCL and APS enhanced the antigen-specific CD8+ T cell response and suppressed the growth of tumors in mouse models with good biocompatibility.Conclusion: We successfully prepared a nanovaccine termed NP-TCL@APS, which can promote the maturation of DC and induce strong responses by T lymphocytes to exert anti-tumor effects. The strategy proposed here is promising for generating a tumor vaccine and can be extended to various types of cancers.Keywords: colorectal cancer, nanovaccine, PLGA, Astragalus polysaccharide, tumor cell lysates (TCL)

Abstract Background Alveolar Bone loss occurs frequently during the first six months after tooth extraction. Various studies have proposed different methods to reduce as much as possible the atrophy of the alveolar ridge after tooth extraction. Filling the socket with biomaterials after extraction can reduce the resorption of the alveolar ridge. We compared the height of the alveolar process at the mesial and distal aspects of the extraction site and the resorption rate was calculated after the application of HA/β-TCP or synthetic co-polymer polyglycolic - polylactic acid PLGA mixed with blood to prevent socket resorption immediately and after tooth extraction. Methods The study was conducted on 24 extraction sockets of impacted mandibular third molars bilaterally, vertically, and completely covered, with a thin bony layer. HA/β-TCP was inserted into 12 of the dental sockets immediately after extraction, and the synthetic polymer PLGA was inserted into 12 of the dental sockets. All sockets were covered completely with a full-thickness envelope flap. Follow-up was performed for one year after extraction, using radiographs and stents for the vertical alveolar ridge measurements. Results The mean resorption rate in the HA/β-TCP and PLGA groups was ± 1.23 mm and ± 0.1 mm, respectively. A minimal alveolar bone height reduction of HA/β-TCP was observed after 9 months, the reduction showed a slight decrease to 0.93 mm, while this rate was 0.04 mm after 9 months in the PLGA group. Moreover, the bone height was maintained after three months, indicating a good HA/β-TCP graft performance in preserving alveolar bone (1.04 mm) while this rate was (0.04 mm) for PLGA. Conclusion The PLGA graft demonstrated adequate safety and efficacy in dental socket preservation following tooth extraction. However, HA/β-TCP causes greater resorption at augmented sites than PLGA, which clinicians should consider during treatment planning.

The use of stem cell-based treatment systems is prevalent in regenerative medicine. To enhance the regenerative capabilities of stem cells, growth factors are typically incorporated into the treatment system. Nonetheless, traditional hydrogel-encapsulated or heparinized scaffolds that bind factors have limitations. In this study, we prepared a biomaterial strategy using uniform poly(lactic-co-glycolic) acid (PLGA) microspheres (uPLGA-Ms) fabricated by microfluidic to sustain delivery of insulin-like growth factor 1 (IGF-1), a critical protein for hMSCs biological functions. The uPLGA-Ms loaded IGF-1 were highly monodispersed through precise manipulation of the flow rate of the two-phase of the flow-focusing microchannle. The results showed that the uPLGA-Ms stabilize IGF-1 and provide a more efficient sustained delivery and cost-effective of growth factor. Gene expression analysis demonstrated the uPLGA delivery of IGF-1 results in a (enhanced) supported hMSCs expansion, survival, stemness, and secretion abilities comparable with the conventional soluble IGF-1 group. In summary, this material-based strategy to stabilize and sustain delivery of growth factor has broad potential to regeneration of various tissues and organs.

[Display omitted] Here we demonstrate for the first time that an antibody-gold nanoparticles (AuNPs)–polymer conjugate thin-film biosensor can easily be fabricated to selectively capture Tau protein. Gold nanoparticles (AuNPs) are employed as sensing elements, thus capitalizing on their propensity to undergo assembly or disassembly in response to the adsorption or conjugation of various biomolecules on their surface, thereby forming robust interactions with the target analyte. We show that the Tau protein in its different aggregation phases can be detected, by restricting the reaction area on the solid thin polymer film and thus reducing the diffusion effects usually encountered in immunosensors. A limit of detection (LOD) of 460 pg/mL was reached, demonstrating a great potential for detecting Tau in aggregation states. This sensor based on thin polymer film could open new routes for sensing and monitoring Tau protein in biological assays and biomedical diagnosis. [ABSTRACT FROM AUTHOR]

Cancer is a leading cause of death worldwide, and imposes a substantial socioeconomic burden with little impact especially on aggressive types of cancer. Conventional therapies have many serious side effects including generalised systemic toxicity which limits their long-term use. Tumour resistance and recurrence is another main problem associated with conventional therapy. Purified or extracted natural products have been investigated as cost-effective cancer chemoprotective agents with the potential to reverse or delaying carcinogenesis. Curcumin (CUR) as a natural polyphenolic component, exhibits many pharmacological activities such as anti-cancer, anti-inflammatory, anti-microbial, activity against neurodegenerative diseases including Alzheimer, antidiabetic activities (type II diabetes), anticoagulant properties, wound healing effects in both preclinical and clinical studies. Despite these effective protective properties, CUR has several limitations, including poor aqueous solubility, low bioavailability, chemical instability, rapid metabolism and a short half-life time. To overcome the pharmaceutical problems associated with free CUR, novel nanomedicine strategies (including polymeric nanoparticles (NPs) such as poly (lactic-co-glycolic acid) (PLGA) NPs have been developed. These formulations have the potential to improve the therapeutic efficacy of curcuminoids. In this review, we comprehensively summarise and discuss recent in vitro and in vivo studies to explore the pharmaceutical significance and clinical benefits of PLGA-NPs delivery system to improve the efficacy of CUR in the treatment of cancer. [ABSTRACT FROM AUTHOR]

Purpose: Prednisolone, a synthetic corticosteroid drug, is extensively utilized to treat inflammatory diseases and regulates metabolism and the immune system in cancer treatment. However, these drugs are toxic and cause severe side effects if administrated for long durations and in large doses. This work intends to study the atomistic interactions of popular polymeric carrier like PLGA with the drug and thereby provide insights into achieving better loading and a sustained release. Methods: Molecular dynamics (MD) simulations of prednisolone (drug) encapsulated in Poly Lactic-co-Glycolic acid (PLGA) are performed in this study. Grand Canonical Monte Carlo (GCMC) simulations with MD simulations are conducted to determine the water penetration in PLGA polymer and polymer stability in water. The investigations from this study encompasses structural and dynamical parameters, including the end-to-end distance, radius of gyration of polymer chains, interaction energy, and diffusion coefficient of the drug. Results: The polymer-drug interactions are studied and identified from the simulation data of PLGA(75:25) and PLGA(50:50) polymers with prednisolone in an aqueous medium for optimal drug carrying capacity and effective drug release. Also, the polymeric systems of PLGA(75:25) and PLGA(50:50) are analyzed with the water penetrant loading using the Grand Canonical Monte Carlo (GCMC) and MD simulations. Water loading analysis revealed that PLGA(75:25) has the highest swelling compared to PLGA(50:50). Conclusion: This study highlights the characteristics and critical parameters for developing an optimal drug delivery system by investigating polymer-drug interactions, drug encapsulation, and water uptake in polymers using MD and GCMC simulations. [ABSTRACT FROM AUTHOR]

Abstract Background Colorectal cancer is a common disease worldwide with non-specific symptoms such as blood in the stool, bowel movements, weight loss and fatigue. Chemotherapy drugs can cause side effects such as nausea, vomiting and a weakened immune system. The use of antioxidants such as hesperidin could reduce the side effects, but its low bioavailability is a major problem. In this research, we aimed to explore the drug delivery and efficiency of this antioxidant on the HCT116 colorectal cancer cell line by loading hesperidin into PLGA nanoparticles. Materials and methods Hesperidin loaded PLGA nanoparticles were produced by single emulsion evaporation method. The physicochemical properties of the synthesized hesperidin-loaded nanoparticles were determined using SEM, AFM, FT-IR, DLS and UV-Vis. Subsequently, the effect of the PLGA loaded hesperidin nanoparticles on the HCT116 cell line after 48 h was investigated by MTT assay at three different concentrations of the nanoparticles. Result The study showed that 90% of hesperidin were loaded in PLGA nanoparticles by UV-Vis spectrophotometry and FT-IR spectrum. The nanoparticles were found to be spherical and uniform with a hydrodynamic diameter of 76.2 nm in water. The release rate of the drug was about 93% after 144 h. The lowest percentage of cell viability of cancer cells was observed at a concentration of 10 µg/ml of PLGA nanoparticles loaded with hesperidin. Conclusion The results indicate that PLGA nanoparticles loaded with hesperidin effectively reduce the survival rate of HCT116 colorectal cancer cells. However, further studies are needed to determine the appropriate therapeutic dosage and to conduct animal and clinical studies.

Telomerase activity is directly affected by the laminin receptor precursor (LRP) protein, a highly conserved nonintegrin transmembrane receptor, which has been shown to have therapeutic effects in ageing, and age‐related diseases. Recently, it has been found that overexpression of LRP‐FLAG, by plasmid transfection, leads to a significant increase in telomerase activity in cell culture models. This may indicate that upregulation of LRP can be used to treat various age‐related diseases. However, transfection is not a viable treatment strategy for patients. Therefore, we present a nanoencapsulated protein‐based drug synthesised using poly(lactic‐co‐glycolic acid) (PLGA) nanocapsules for delivery of the 37 kDa LRP protein therapeutic. PLGA nanocapsules were synthesised using the double emulsification‐solvent evaporation technique. Different purification methods, including filtration and centrifugation, were tested to ensure that the nanocapsules were within the optimal size range, and the BCA assay was used to determine encapsulation efficiency. The completed drug was tested in a HEK‐293 cell culture model, to investigate the effect on cell viability, LRP protein levels and telomerase activity. A significant increase in total LRP protein levels with a concomitant increase in cell viability and telomerase activity was observed. Due to the observed increase in telomerase activity, this approach could represent a safer alternative to plasmid transfection for the treatment of age‐related diseases.

الملخص: تطور مرض ألزهايمر كنتيجة لتكوين علامتين رئيسيتين، والتي تتضمن تشكيل طفيليات البيتا-أميلويد خارج الخلو وفرط فسفرة بروتين الـ تاو، مما يؤدي إلى تشكل عقد عصبية متعرجة. تؤدي هاتان العلامتان إلى فقدان التآزر بين الخلايا العصبية، وتلف الخلايا العصبية، وتطوير الالتهاب العصبي والإجهاد التأكسدي، مما يعزز تقدم المرض. لذلك، يهدف علاج مرض ألزهايمر إلى القضاء على هذه العلامات الرئيسية لمنع تقدم المرض وتقليل الأعراض. ومع ذلك، فإن العلاج الحالي المتوفر في السوق يوفر تخفيفا أعراضيا بدلا من معالجة السبب الأساسي للمرض. ويعزى هذا إلى الطبيعة المقيدة لحاجز الدماغ-الدم التي تعوق دخول الأدوية، مما يؤثر على فعالية الدواء وقابليته للامتصاص. يركز الباحثون على تطوير طرق علاجية جديدة يمكن أن تتجاوز حاجز الدماغ-الدم، لتوفير توصيل الدواء إلى الموقع المحدد مع أقصى قابلية امتصاص ممكنة وأقل آثار جانبية. من بين الاستراتيجيات العلاجية الجديدة المكتشفة هي استخدام البيولوجيات كأضداد أحادية النسيلة. واقترح اداكونوماب مرشحا قويا لعلاج مرض ألزهايمر وحصل على موافقة مسرعة من إدارة الغذاء والدواء، ومع ذلك، فإن مخاوف السلامة قد تحول دون استخدامه في المستقبل. وبالتالي، تشكل التقنية النانوية عصرا جديدا لعلاج مرض ألزهايمر، نظرا للسمات المميزة التي توفرها جزيئات النانو من حيث اجتياز حاجز الدماغ-الدم بسبب حجمها الصغير، وتعزيز الخصائص الدوائية للأدوية وتوصيل الدواء المستهدف. تدرس جزيئات النانو البوليمرية بشكل موسع في الوقت الراهن، نظرا لسهولة وبساطة طريقة إنتاجها، والتحلل البيولوجي، والتوافق البيولوجي والهيكل الفريد الذي يوفر وعاء مرن يمكن تعديله بسهولة لتحقيق الخصائص الفيزيوكيميائية المرغوبة. وبالتالي، سيتم مناقشة أنواع مختلفة من جزيئات النانو القائمة على البوليمر في هذه المراجعة، مع تسليط الضوء على الخصائص التي توفرها جزيئات النانو المصنعة والتي تظهر العديد من الفوائد في علاج مرض ألزهايمر. تشمل هذه الخصائص التأثيرات المضادة للأميلويد والمضادة للأكسدة والمضادة للالتهابات. Abstract: Alzheimer's disease (AD), is characterised by two major hallmarks: the formation of extracellular β-amyloid (Aβ) plaques and the hyperphosphorylation of tau protein, thus leading to the formation of neurofibrillary tangles. These hallmarks cause synaptic loss, neuronal damage, and the development of neuroinflammation and oxidative stress, which promote AD progression. Thus, the goal of treating AD is eliminating these hallmarks, to prevent AD progression and decrease symptoms. However, current available therapies provide symptomatic relief rather than treating the underlying cause of the disease, because the restrictive nature of the blood brain barrier (BBB) impedes the entry of drugs, thereby affecting drug efficacy and bioavailability. Researchers are focusing on developing new therapeutic approaches to bypass the BBB, for achieving site-specific drug delivery with the highest possible bioavailability and the lowest adverse effects. Recently explored therapeutic strategies include use of biologic agents such as monoclonal antibodies. Aducanumab, a strong candidate for treating AD, has been granted accelerated Food and Drug Administration approval; however, safety concerns may hinder its future use. Thus, nanotechnological approaches have led to a new era of AD treatment. Nanoparticles (NPs), because of their small particle size, can cross the BBB, thus enhancing drug pharmacokinetic properties and enabling targeted drug delivery. Polymeric NPs have been extensively studied, because of their simple production, biodegradability, biocompatibility, and unique architecture. These NPs provide a flexible vesicle that can be easily tailored to achieve desired physicochemical features. In this review, various types of polymer-based-NPs are discussed, highlighting the properties of fabricated NPs, which have multiple benefits in AD treatment, including anti-amyloid, antioxidant, and anti-inflammatory effects.

AbstractPrimaquine (PQ) is a widely used antimalarial drug, but its high dosage requirements can lead to significant tissue damage and adverse gastrointestinal and hematological effects. Recent studies have shown that nanoformulations can enhance the bioavailability of pharmaceuticals, thereby increasing efficacy, reducing dosing frequency, and minimizing toxicity. In this study, PQ-loaded PLGA nanoparticles (PQ-NPs) were prepared using a modified double emulsion solvent evaporation technique (w/o/w). The PQ-NPs exhibited a mean particle size of 228 ± 2.6 nm, a zeta potential of +27.4 mV, and an encapsulation efficiency of 81.3 ± 3.5%. Scanning electron microscopy (SEM) confirmed their spherical morphology, and the in vitro release profile demonstrated continuous drug release over 72 h. Differential scanning calorimetry (DSC) thermograms indicated that the drug was present in the nanoparticles, with improved physical stability. Fourier-transform infrared spectroscopy (FTIR) analysis showed no interactions between the various substances in the NPs. In vivo studies in Swiss albino mice infected with Plasmodium berghei revealed that the nanoformulated PQ was 20% more effective than the standard oral dose. Biodistribution studies indicated that 80% of the NPs accumulated in the liver, highlighting their potential for targeted drug delivery. This research demonstrates the successful development of a nanomedicine delivery system for antimalarial drugs, offering a promising strategy to enhance treatment efficacy while reducing adverse effects. [ABSTRACT FROM AUTHOR]

The present study examined current research trends on copolymers' role in lung cancer by using bibliometric analysis and to identify the areas for further research. Through the use of the Scopus database, this study gathered 736 records that were published between 1974 and 2023. Based on the research findings, block copolymers emerged as a distinctive approach for the treatment of lung cancer and various other malignancies. However, since 1974, this industry has grown rapidly. No bibliometric studies have been done on this topic to analyse the research landscape and indicate research trends and hotspots. VOSviewer was used for bibliometric analysis and visualisation. Over the last 49 years, the results of the yearly publication and citation demonstrated substantial growing tendencies across the period. The United States of America and China have been the primary driving forces in this sector, and this has contributed to the total number of publications. [ABSTRACT FROM AUTHOR]

Aim: The aim of current study is the development and optimization of biodegradable polymeric nanoparticles (NPs) to be used in the field of Endodontics as intracanal medication in cases of avulsed teeth with extended extra‐oral time, utilizing PLGA polymers loaded with the anti‐inflammatory drug clobetasol propionate (CP). Methodology: CP‐loaded nanoparticles (CP‐NPs) were prepared using the solvent displacement method. CP release profile from CP‐NPs was assessed for 48 h against free CP. Using extracted human teeth, the degree of infiltration inside the dentinal tubules was studied for both CP‐NPs and CP. The anti‐inflammatory capacity of CP‐NPs was evaluated in vitro measuring their response and reaction against inflammatory cells, in particular against macrophages. The enzyme‐linked immunosorbent assay (ELISA) was used to examine the cytokine release of IL‐1β and TNF‐α. Results: Optimized CP‐NPs displayed an average size below 200 nm and a monomodal population. Additionally, spherical morphology and non‐aggregation of CP‐NPs were confirmed by transmission electron microscopy. Interaction studies showed that CP was encapsulated inside the NPs and no covalent bonds were formed. Moreover, CP‐NPs exhibited a prolonged and steady release with only 21% of the encapsulated CP released after 48 h. Using confocal laser scanning microscopy, it was observed that CP‐NPs were able to display enhanced penetration into the dentinal tubules. Neither the release of TNF‐α nor IL‐1β increased in CP‐NPs compared to the LPS control, displaying results similar and even less than the TCP after 48 h. Moreover, IL‐1β release in LPS‐stimulated cells, decreased when macrophages were treated with CP‐NPs. Conclusions: In the present work, CP‐NPs were prepared, optimized and characterized displaying significant increase in the degree of infiltration inside the dentinal tubules against CP and were able to significantly reduce TNF‐α release. Therefore, CP‐NPs constitute a promising therapy for the treatment of avulsed teeth with extended extra‐oral time. [ABSTRACT FROM AUTHOR]

This paper presents an experimental study on preparation of tramadol hydrochloride (TrH) loaded nanoparticles, and stability determination in various infusion solutions. In this study, various nanoparticle preparation parameters based on w/o/w emulsification solvent evaporation method, including stabilizer type, stabilizer concentration, polymer concentration, homogenization speed and initial drug amount were systematically tested to verify their versatility for preparing nanoparticles. Initially both particle size and encapsulation efficiency of nanoparticles were changed significantly with the change in surfactant and polymer ratio (p<0.05). However, homogenization speed only changed particle size (average size 339.3±1.8 nm for 15000 rpm, 318.9±6.4 nm for 20000 rpm and 237.2±7.8 nm for 25000 rpm) (p<0.05) and initial drug concentration is only affected the encapsulation efficiency (34.2±0.7% for 4 mg/mL and 33.2±0.9 for 1.6 mg/mL) (p<0.05). Storage at room temperature for 3 months resulted in an increase in particle size and polydispersity index. Prepared nanoparticles showed the best stability after storage at – 20 °C for in 3 months. Finally, storage of nanoparticles in various infusion solutions resulted an undesirable changes for 6% Hydroxyethyl starch in 0.9% sodium chloride injection, 10% Dextran 40 and 4% Succinyl gelatin solutions. It was shown that an appropriate delivery of TrH loaded PLGA nanoparticles as infusion can be prepared only in water for injection, 20% Mannitol, 0.9% Sodium chloride and 5% Dextrose solutions. [ABSTRACT FROM AUTHOR]

Accurately measuring drug and its release kinetics in both in vitro and in vivo environments is crucial for enhancing therapeutic effectiveness while minimizing potential side effects. Nevertheless, the real-time visualization of drug release from microspheres to monitor potential overdoses remains a challenge. The primary objective of this investigation was to employ fluorescence imaging for the real-time monitoring of drug release from microspheres in vitro, thereby simplifying the laborious analysis associated with the detection of drug release. Two distinct varieties of microspheres were fabricated, each encapsulating different drugs within PLGA polymers. Cy5 was selected as the donor, and Cy7 was selected as the acceptor for visualization and quantification of the facilitated microsphere drug release through the application of the fluorescence resonance energy transfer (FRET) principle. The findings from the in vitro experiments indicate a correlation between the FRET fluorescence alterations and the drug release profiles of the microspheres. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is a common disease worldwide with non-specific symptoms such as blood in the stool, bowel movements, weight loss and fatigue. Chemotherapy drugs can cause side effects such as nausea, vomiting and a weakened immune system. The use of antioxidants such as hesperidin could reduce the side effects, but its low bioavailability is a major problem. In this research, we aimed to explore the drug delivery and efficiency of this antioxidant on the HCT116 colorectal cancer cell line by loading hesperidin into PLGA nanoparticles. Materials and methods: Hesperidin loaded PLGA nanoparticles were produced by single emulsion evaporation method. The physicochemical properties of the synthesized hesperidin-loaded nanoparticles were determined using SEM, AFM, FT-IR, DLS and UV-Vis. Subsequently, the effect of the PLGA loaded hesperidin nanoparticles on the HCT116 cell line after 48 h was investigated by MTT assay at three different concentrations of the nanoparticles. Result: The study showed that 90% of hesperidin were loaded in PLGA nanoparticles by UV-Vis spectrophotometry and FT-IR spectrum. The nanoparticles were found to be spherical and uniform with a hydrodynamic diameter of 76.2 nm in water. The release rate of the drug was about 93% after 144 h. The lowest percentage of cell viability of cancer cells was observed at a concentration of 10 µg/ml of PLGA nanoparticles loaded with hesperidin. Conclusion: The results indicate that PLGA nanoparticles loaded with hesperidin effectively reduce the survival rate of HCT116 colorectal cancer cells. However, further studies are needed to determine the appropriate therapeutic dosage and to conduct animal and clinical studies. [ABSTRACT FROM AUTHOR]

This study explores the impact of varying temperatures on the release behavior of Triptorelin Acetate (TA) from a PLGA-based in-situ forming implant (ISFI) and polymer degradation. Formulations were prepared using the in situ forming method in an acetate buffer (pH = 6.8) and then exposed to temperatures of 4 to 60 °C. The drug release and polymeric depot behavior were evaluated using HPLC, SEM, GPC, Rheometer, and pH measurements. A modified Gallagher-Corrigan Model-based mathematical model was applied to fit the in-vitro data, and the activation energy for peptide release in diffusional and erosional phases was calculated using the Arrhenius equation. The results revealed that matrices formed at 37, 45, and 53 °C exhibited a highly porous structure, resulting from rapid phase inversion and surface pore closing. This led to a reduction in TA burst release, observed as 38%, 27%, and 15% at 37 °C, 45 °C, and 53 °C respectively. Conversely, matrices at 4 and 25 °C demonstrated a faster initial release, followed by the formation of dense structures. The accelerated drug release profiles at 45 and 53 °C showed a shortened ultimate drug release duration and a good correlation with the real-time results at 37 °C. Due to the discernible PLGA matrices degradation at different temperatures, biphasic and tri-phasic release patterns were observed. The experimental release results aligned well with the proposed mathematical model, and the drug release kinetic parameters were estimated. Thus, in in-vitro studies, the release medium temperature plays a significant role in the drug-release behavior of ISFIs. [ABSTRACT FROM AUTHOR]

Nanoparticles (NPs) engineered as drug delivery systems continue to make breakthroughs as they offer numerous advantages over free therapeutics. However, the poor understanding of the interplay between the NPs and biomolecules, especially blood proteins, obstructs NP translation to clinics. Nano-bio interactions determine the NPs' in vivo fate, efficacy and immunotoxicity, potentially altering protein function. To fulfill the growing need to investigate nano-bio interactions, this study provides a systematic understanding of two key aspects: (i) protein corona (PC) formation and (ii) NP-induced modifications on protein's structure and stability. A methodology was developed by combining orthogonal techniques to analyze both quantitative and qualitative aspects of nano-bio interactions, using human serum albumin (HSA) as a model protein. Protein quantification via liquid chromatography-mass spectrometry, and capillary zone electrophoresis (CZE) clarified adsorbed protein quantity and stability. CZE further unveiled qualitative insights into HSA forms (native, glycated HSA and cysteinylated), while synchrotron radiation circular dichroism enabled analyzing HSA's secondary structure and thermal stability. Comparative investigations of NP cores (organic vs. hybrid), and shells (with or without polyethylene glycol (PEG)) revealed pivotal factors influencing nano-bio interactions. Polymeric NPs based on poly(lactic-co-glycolic acid) (PLGA) and hybrid NPs based on metal-organic frameworks (nanoMOFs) presented distinct HSA adsorption profiles. PLGA NPs had protein-repelling properties while inducing structural modifications on HSA. In contrast, HSA exhibited a high affinity for nanoMOFs forming a PC altering thereby the protein structure. A shielding effect was gained through PEGylation for both types of NPs, avoiding the PC formation as well as the alteration of unbound HSA structure. [ABSTRACT FROM AUTHOR]

While long-acting injectable treatments are gaining increasing interest in managing chronic diseases, the available drug delivery systems almost exclusively rely on hydrophobic matrixes, limiting their application to either hydrophobic drugs or large and hydrophilic molecules such as peptides. To address the technological lock for long-acting delivery systems tailored to small, hydrophilic drugs such as anticancer and antiviral nucleoside/nucleotide analogues, we have synthesized and characterized an original approach with a multi-scale structure: (i) a nucleotide (adenosine triphosphate, ATP) is first incorporated in hydrophilic chitosan-Fe(III) nanogels; (ii) these nanogels are then transferred by freeze-drying and resuspension into a water-free, hydrophobic medium containing PLGA and an organic solvent, N-methyl-2-pyrrolidone. We show that this specific association allows an injectable and homogeneous dispersion, able to form in situ implants upon injection in physiological or aqueous environments. This system releases ATP in vitro without any burst effect in a two-step mechanism, first as nanogels acting as an intermediate reservoir over a week, then as free drug over several weeks. In vivo studies confirmed the potential of such nanostructured implants for sustained drug release following subcutaneous injection to mice hock, opening perspectives for sustained and targeted delivery through the lymphatic system. [ABSTRACT FROM AUTHOR]

Biodegradable nanocarriers possess enormous potential for use as drug delivery systems that can accomplish controlled and targeted drug release, and a wide range of nanosystems have been reported for the treatment and/or diagnosis of various diseases and disorders. Of the various nanocarriers currently available, liposomes and polymer nanoparticles have been extensively studied and some formulations have already reached the market. However, a combination of properties to create a single hybrid system can give these carriers significant advantages, such as improvement in encapsulation efficacy, higher stability, and active targeting towards specific cells or tissues, over lipid or polymer-based platforms. To this aim, this work presents the formulation of poly(lactic-co-glycolic) acid (PLGA) nanoparticles in the presence of a hyaluronic acid (HA)-phospholipid conjugate (HA-DPPE), which was used to anchor HA onto the nanoparticle surface and therefore create an actively targeted hybrid nanosystem. Furthermore, ionic interactions have been proposed for drug encapsulation, leading us to select the free base form of pentamidine (PTM-B) as the model drug. We herein report the preparation of hybrid nanocarriers that were loaded via ion-pairing between the negatively charged PLGA and HA and the positively charged PTM-B, demonstrating an improved loading capacity compared to PLGA-based nanoparticles. The nanocarriers displayed a size of below 150 nm, a negative zeta potential of -35 mV, a core-shell internal arrangement and high encapsulation efficiency (90%). Finally, the ability to be taken up and exert preferential and receptor-mediated cytotoxicity on cancer cells that overexpress the HA specific receptor (CD44) has been evaluated. Competition assays supported the hypothesis that PLGA/HA-DPPE nanoparticles deliver their cargo within cells in a CD44-dependent manner. [ABSTRACT FROM AUTHOR]

Aim: RADA16-PLGA composite scaffolds constructed with simultaneous loading of BMSCs and TGF-β3 and explored their ability for chondrogenic differentiation in vitro. Methods: The performance of the composite scaffolds is assessed by rheometer assay, electron microscopic structural observation and ELISA release assay. The biosafety of the composite scaffolds is assessed by cytocompatibility assay and cell migration ability. The chondrogenic differentiation ability of composite scaffolds is evaluated by Alisin blue staining, PCR and immunofluorescence staining. Results: The composite scaffold has a good ECM-like structure, the ability to control the release of TGF-β3 and good biocompatibility. More importantly, the composite scaffolds can induce the differentiation of BMSCs to chondrocytes. Conclusion: Composite scaffolds are expected to enhance the endogenous NP repair process. Graphical Abstract RADA16 aqueous solution, PLGA microspheres and BMSCs are mixed to form a composite aqueous solution. The aqueous solution is injected into the body and exposed to the acidic environment of the NP. The nucleus pulposus pH induces gelation of the aqueous solution to form a composite scaffold. The composite scaffold can function in vivo. It induces the differentiation of BMSCs into chondrocytes and subsequently secretes a large amount of ECM such as Collagen II, GAGAs and SOX-9. In addition, it also enhances the self-repair of endogenous BMSCs, which is to replenish the reduction of nucleus pulposus cells and the loss of ECM. Article highlights There is an endogenous repair process during myeloid degeneration, but there is an insufficient number of stem cells and a lack of sustained release of growth factors. BMSCs can differentiate into chondrocytes and secrete extracellular matrix in response to TGFβ3. The physico-mechanical properties and ultrastructure of the RADA16 hydrogel meet the requirements of the target material. The suitable conditions for RADA16 are 1% w/v and pH = 7.0. The RADA16-PLGA hydrogel-microsphere composite scaffold structure can encapsulate TGF-β3 to form a good controlled release system. The suitable conditions for the composite scaffold are 1% w/v and pH = 7.0. Composite scaffolds have good cytocompatibility. Composite scaffolds can recruit BMSCs for migration to the composite scaffold. The composite scaffold can adapt to the acidic environment of the degenerated disc, inducing the differentiation of BMSCs to chondrocyte-like cells while secreting large amounts of ECM. Composite scaffolds are expected to enhance the endogenous NP repair process and are promising tissue-engineered scaffolds for IVDD repair. [ABSTRACT FROM AUTHOR]

Introduction: Allergic rhinitis (AR) is an upper airway inflammatory disease of the nasal mucosa. Conventional treatments such as symptomatic pharmacotherapy and allergen-specific immunotherapy have considerable limitations and drawbacks. As an emerging therapy with regenerative potential and immunomodulatory effect, mesenchymal stem cell-derived exosomes (MSC-Exos) have recently been trialed for the treatment of various inflammatory and autoimmune diseases. Methods: In order to achieve sustained and protected release of MSC-Exos for intranasal administration, we fabricated Poly(lactic-co-glycolic acid) (PLGA) micro and nanoparticles-encapsulated MSC-Exos (PLGA-Exos) using mechanical double emulsion for local treatment of AR. Preclinical in vivo imaging, ELISA, qPCR, flow cytometry, immunohistochemical staining, and multiomics sequencing were used for phenotypic and mechanistic evaluation of the therapeutic effect of PLGA-Exos in vitro and in vivo. Results: The results showed that our PLGA platform could efficiently encapsulate and release the exosomes in a sustained manner. At protein level, PLGA-Exos treatment upregulated IL-2, IL-10 and IFN-γ, and downregulated IL-4, IL-17 and antigen-specific IgE in ovalbumin (OVA)-induced AR mice. At cellular level, exosomes treatment reduced Th2 cells, increased Tregs, and reestablished Th1/Th2 balance. At tissue level, PLGA-Exos significantly attenuated the infiltration of immune cells (e.g., eosinophils and goblet cells) in nasal mucosa. Finally, multiomics analysis discovered several signaling cascades, e.g., peroxisome proliferator-activated receptor (PPAR) pathway and glycolysis pathway, that might mechanistically support the immunomodulatory effect of PLGA-Exos. Discussion: For the first time, we present a biomaterial-facilitated local delivery system for stem cell-derived exosomes as a novel and promising strategy for AR treatment. [ABSTRACT FROM AUTHOR]