Search

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]

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]

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]

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]

Abstract: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 generalized systemic toxicity which limits their long-term use. Tumor 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 summarize 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]

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]

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]

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]

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]

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]

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]

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.

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.

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.

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.

Abstract Brucellosis poses a significant challenge in the medical field as a systemic infection with a propensity for relapse. This study presented a novel approach to brucellosis treatment, enhancing the efficacy of doxycycline and rifampicin through the use of poly (lactic-co-glycolic) acid coupled with cadmium-telluride quantum dots (Dox-Rif-PLGA@CdTe). The double emulsion solvent evaporation method was employed to prepare Dox-Rif-PLGA@CdTe. The study scrutinized the physicochemical attributes of these nanoparticles. The impact of antibiotic-loaded nanoparticles on Brucella melitensis was evaluated through well diffusion, minimum inhibitory concentration (MIC), and cell culture. The chemical analysis results demonstrated a possibility of chemical reactions occurring among the constituents of nanoparticles. Assessments using the well diffusion and MIC methods indicated that the impact of free drugs and nanoparticles on bacteria was equivalent. However, the drug-loaded nanoparticles significantly decreased the colony-forming units (CFUs) within the cell lines compared to free drugs. In conclusion, the synthesis of nanoparticles adhered to environmentally friendly practices and demonstrated safety. The sustained drug release over 100 h facilitated drug accumulation at the bacterial site, resulting in a heightened therapeutic effect on B. melitensis and improved outcomes in brucellosis treatment. The application of these synthesized nanodrugs exhibited promising therapeutic potential.

Background: With the global increase in antibacterial resistance, the challenge faced by developing countries is to utilize the available antibiotics, alone or in combination, against resistant bacterial strains. We aimed to encapsulate the levofloxacin (LVX) into polymeric nanoparticles using biodegradable polymers i.e. Chitosan and PLGA, estimating their physicochemical characteristics followed by functional assessment as nanocarriers of levofloxacin against the different resistant strains of bacteria isolated from biological samples collected from tertiary care hospital in Lahore, Pakistan. Methods: LVX-NPs were synthesized using ion gelation and double emulsion solvent-evaporation method employing chitosan (CS) and poly-lactic-co-glycolic acid (PLGA), characterized via FTIR, XRD, SEM, and invitro drug release studies, while antibacterial activity was assessed using Kirby-Bauer disc-diffusion method. Results: Data revealed that the levofloxacin-loaded chitosan nanoparticles showed entrapment efficiency of 57.14% ± 0.03 (CS-I), 77.30% ± 0.08(CS-II) and 87.47% ± 0.08 (CS-III). The drug content, particle size, and polydispersity index of CS-I were 52.22% ± 0.2, 559 nm ± 31 nm, and 0.030, respectively, whereas it was 66.86% ± 0.17, 595 nm ± 52.3 nm and 0.057, respectively for CS-II and 82.65% ± 0.36, 758 nm ± 24 nm and 0.1, respectively for CS-III. The PLGA-levofloxacin nanoparticles showed an entrapment efficiency of 42.80% ± 0.4 (PLGA I) and 23.80% ± 0.4 (PLGA II). The drug content, particle size and polydispersity index of PLGA-I were 86% ± 0.21, 92 nm ± 10 nm, and 0.058, respectively, whereas it was 52.41% ± 0.45, 313 nm ± 32 nm and 0.076, respectively for PLGA-II. The XRD patterns of both polymeric nanoparticles showed an amorphous nature. SEM analysis reflects the circular-shaped agglomerated nanoparticles with PLGA polymer and dense spherical nanoparticles with chitosan polymer. The in-vitro release profile of PLGA-I nanoparticles showed a sustained release of 82% in 120 h and it was 58.40% for CS-III. Both types of polymeric nanoparticles were found to be stable for up to 6 months without losing any major drug content. Among the selected formulations, CS-III and PLGA-I, CS-III had better antibacterial potency against gram+ve and gram-ve bacteria, except for K. pneumonia, yet, PLGA-I demonstrated efficacy against K. pneumonia as per CSLI guidelines. All formulations did not exhibit any signs of hemotoxicity, nonetheless, the CS-NPs tend to bind on the surface of RBCs. Conclusion: These data suggested that available antibiotics can effectively be utilized as nano-antibiotics against resistant bacterial strains, causing severe infections, for improved antibiotic sensitivity without compromising patient safety.

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]

Nanoparticles (NPs) have become attractive vehicles for drug delivery in cancer therapy due to their ability to accumulate in tumours and mitigate side effects. This study focuses on the production of doxorubicin (DOX)-loaded NPs comprising Poly (lactic-co-glycolic acid)-Polyethylene glycol with varying PEG proportions and the examination of their impact on drug release kinetics. DOX-loaded NPs, composed of PLGA-co-PEG with PEG contents of 0%, 5%, 10%, and 15%, were synthesized by the solvent evaporation technique, exhibited spherical morphology, and had sizes ranging from 420 nm to 690 nm. In vitro drug release studies revealed biphasic profiles, with higher PEG contents leading to faster and more extensive drug release. The Baker–Lonsdale model demonstrated the best fit to the drug release data, indicating that the release process is diffusion-controlled. The diffusion coefficients for DOX determined ranged from 6.3 × 10−18 to 7.55 × 10−17 cm2s−1 and exhibited an upward trend with increasing PEG content in the polymer. In vitro cytotoxicity tests with CHO cells showed that unloaded NPs are non-toxic, while DOX-loaded PLGA-PEG 15% NPs induced a greater decrease in cellular viability compared to their PLGA counterparts. A mathematical relationship between the diffusion coefficient and PEG percentage was derived, providing a practical tool for optimizing DOX release profiles. [ABSTRACT FROM AUTHOR]

AbstractBurn 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]

Aim: Design, produce and assess the viability of a novel nanotechnological antibacterial thermo‐sensible intracanal medicament This involves encapsulating calcium hydroxide (Ca(OH)2) within polylactic‐co‐glycolic acid (PLGA) nanoparticles (NPs) and dispersing them in a thermosensitive gel (Ca(OH)2‐NPs‐gel). In addition, perform in vitro and ex vivo assessments to evaluate tissue irritation and penetration capacity into dentinal tubules in comparison to free Ca(OH)2. Methodology: Reproducibility of Ca(OH)₂‐NPs was confirmed by obtaining the average size of the NPs, their polydispersity index, zeta potential and entrapment efficiency. Moreover, rheological studies of Ca(OH)2‐NPs‐gel were carried out with a rheometer, studying the oscillatory stress sweep, the mean viscosity value, frequency and temperature sweeps. Tolerance was assessed using the membrane of an embryonated chicken egg. In vitro Ca(OH)2 release was studied by direct dialysis in an aqueous media monitoring the amount of Ca(OH)2 released. Six extracted human teeth were used to study the depth of penetration of fluorescently labelled Ca(OH)2‐NPs‐gel into the dentinal tubules and significant differences against free Ca(OH)2 were calculated using one‐way anova. Results: Ca(OH)2‐NPs‐gel demonstrated to be highly reproducible with an average size below 200 nm, a homogeneous NPs population, negative surface charge and high entrapment efficiency. The analysis of the thermosensitive gel allowed us to determine its rheological characteristics, showing that at 10°C gels owned a fluid‐like behaviour meanwhile at 37°C they owned an elastic‐like behaviour. Ca(OH)2‐NPs‐gel showed a prolonged drug release and the depth of penetration inside the dentinal tubules increased in the most apical areas. In addition, it was found that this drug did not produce irritation when applied to tissues such as eggs' chorialantoidonic membrane. Conclusion: Calcium hydroxide‐loaded PLGA NPs dispersed in a thermosensitive gel may constitute a suitable alternative as an intracanal antibacterial medicament. [ABSTRACT FROM AUTHOR]

Disulfiram (DS) has been shown to have potent anti-cancer activity; however, it is also characterised by its low water solubility and rapid metabolism in vivo. Biodegradable polylactic-co-glycolic acid (PLGA) polymers have been frequently employed in the manufacturing of PLGA nano-carrier drug delivery systems. Thus, to develop DS-loaded PLGA nanoparticles (NPs) capable of overcoming DS's limitations, two methodologies were used to formulate the NPs: direct nanoprecipitation (DNP) and single emulsion/solvent evaporation (SE), followed by particle size reduction. The DNP method was demonstrated to produce NPs of superior characteristics in terms of size (151.3 nm), PDI (0.083), charge (−37.9 mV), and loading efficiency (65.3%). Consequently, NPs consisting of PLGA and encapsulated DS coated with mPEG2k-PLGA at adjustable ratios were prepared using the DNP method. Formulations were then characterised, and their stability in horse serum was assessed. Results revealed the PEGylated DS-loaded PLGA nano-carriers to be more efficient; hence, in-vitro studies testing these formulations were subsequently performed using two distinct breast cancer cell lines, showing great potential to significantly enhance cancer therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This study explored the potential of poly-(lactic-co-glycolic) acid (PLGA) nanoparticles to enhance the effectiveness of anticancer treatments through combination therapy with phytol and α-bisabolol. The encapsulation efficiency of the nanoparticles was investigated, highlighting the role of ionic interactions between the drugs and the polymer. Characterization of PLGA-Phy+Bis nanoparticles was carried out using DLS with zeta potential and HR-TEM for size determination. Spectrophotometric measurements evaluated the encapsulation efficiency, loading efficiency, and in vitro drug release. FTIR analysis assessed the chemical interactions between PLGA and the drug actives, ensuring nanoparticle stability. GC-MS was employed to analyze the chemical composition of drug-loaded PLGA nanocarriers. Cytotoxicity was evaluated via the MTT assay, while Annexin V-FITC/PI staining and western blot analysis confirmed apoptotic cell death. Additionally, toxicity tests were performed on L-132 cells and in vivo zebrafish embryos. The study demonstrates high encapsulation efficiency of PLGA-Phy+Bis nanoparticles, which exhibit monodispersity and sizes of 189.3±5nm (DLS) and 268±54 nm (HR-TEM). Spectrophotometric analysis confirmed efficient drug encapsulation and release control. FTIR analysis revealed nanoparticle structural stability without chemical interactions. MTT assay results demonstrated the promising anticancer potential of all the three nanoparticle types (PLGA-Phy, PLGA-Bis, and PLGA-Phy+Bis) against lung cancer cells. Apoptosis was confirmed through Annexin V-FITC/PI staining and western blot analysis, which also revealed changes in Bax and Bcl-2 protein expression. Furthermore, the nanoparticles exhibited non-toxicity in L-132 cells and zebrafish embryo toxicity tests. PLGA-Phy+Bis nanoparticles exhibited efficient encapsulation, controlled release, and low toxicity. Apoptosis induction in A549 cells and non-toxicity in healthy cells highlight their clinical potential. [ABSTRACT FROM AUTHOR]

Breast cancer is among the most prevalent tumors worldwide. In this study, insitu forming implants (ISFIs) containing rosuvastatin calcium were prepared using three types of poly (D, L-lactic-co-glycolic acid) (PLGA), namely, PLGA 50/50 with ester terminal and PLGA 75/25 with ester or acid terminal. Additionally, polydimethylsiloxane (PDMS) was added in concentrations of 0, 10, 20, and 30% w/v to accelerate matrix formation. The prepared ISFIs were characterized for their rheological behaviors, rate of matrix formation, and invitro drug release. All the prepared formulations revealed a Newtonian flow with a matrix formation rate between 0.017 and 0.059 mm/min. Generally, increasing the concentration of PDMS increased the matrix formation rate. The prepared implants' release efficiency values ranged between 46.39 and 89.75%. The ISFI containing PLGA 50/50 with 30% PDMS was selected for further testing, as it has the highest matrix formation rate and a promising release efficiency value. Copper-selenium nanoparticles were prepared with two different particle sizes (560 and 383 nm for CS1 and CS2, respectively) and loaded into the selected formulation to enhance its anticancer activity. The unloaded and loaded implants with rosuvastatin and copper-selenium nanoparticles were evaluated for their antibacterial activity, against Gram-positive and negative microorganisms, and anticancer efficacy, against MCF-7 and MDA-MB-231 cell lines. The results confirmed the potency of rosuvastatin calcium against cancer cells and the synergistic effect when loaded with smaller particle sizes of copper-selenium nanoparticles. This formulation holds a considerable potential for efficient breast cancer therapy. [ABSTRACT FROM AUTHOR]

Hypothyroidism is a chronic condition combated by a daily oral supplementation of levothyroxine. In addition to the need for frequent dosing, oral administration may result in variable absorption of the drug leading to a failure in achieving normal thyroid function. Therefore, the development of a long-acting injectable system capable of delivering the drug is necessary. This work was aimed at developing sustained release microparticles loaded with levothyroxine. The microparticles were produced through the emulsification-solvent evaporation method using 2 grades of biocompatible and biodegradable polyesters: poly(ᴅ,ʟ-lactide-co-glycolide) (PLGA) and poly(ᴅ,ʟ-lactide) (PLA). Both polymers produced microparticles with very similar sizes (1.9 µm) and zeta potential values (around -22.0 mV). However, PLA microparticles had a significantly higher drug loading (6.1% vs. 4.4%, respectively) and encapsulation efficiency (36.8%, vs. 26.1%, respectively) when compared to PLGA counterparts. While both types of microparticles displayed a biphasic release pattern in vitro , a slower rate of release was observed with PLA microparticles. Moreover, a similar biphasic release pattern was found in vivo , with an initial phase of rapid release followed by a slower phase in the subsequent 10 days. These results indicate the possibility of developing levothyroxine loaded polyester microparticles as a potential long-acting thyroid hormone replacement therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of this work was to evaluate the antineoplastic effect of newly synthesized nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) alone or PLGA esterified with 2,2′-[propane-2,2-diylbis (thio)] diacetic acid (TKL), loaded with docetaxel (DTX) and/or docosahexaenoic acid (DHA), as innovative site-specific therapeutic carriers. The obtained materials were characterized by FT-IR and 1H-NMR, while the dimensional analysis of the nanoparticles obtained was performed by Dynamic Light Scattering. The encapsulation efficiency of the nanoparticles was evaluated, and in vitro skin permeation tests were also performed. The antitumor activity of the nanomaterial was studied in the human adenocarcinoma HCT116 cell line. In particular, viability tests in bidimensional culture, as well as in tumor spheroids, were conducted. The use of these nanocarriers could facilitate the stable and efficient delivery of DTX and DHA through the upper segments of the gastrointestinal tract to the colon. In addition, the presence of the ROS-sensitive 2,2′-[propane-2,2-diylbis (thio)] diacetic acid in their matrix should promote the site-specific release of DTX in the tumor mass, where high levels of reactive oxygen species could be found. [ABSTRACT FROM AUTHOR]

In tissue engineering, electrospinning has gained significant interest due to its highly porous structure with an excellent surface area to volume ratio and fiber diameters that can mimic the structure of the extracellular matrix. Bioactive substances such as growth factors and drugs are easily integrated. In many applications, there is an important need for small tubular structures (I.D. < 1 mm). However, fabricating sub-millimeter structures is challenging as it reduces the collector area and increases the disturbing factors, leading to significant fiber loss. This study aims to establish a reliable and reproducible electrospinning process for sub-millimeter tubular structures with minimized material loss. Influencing factors were analyzed, and disturbance factors were removed before optimizing control variables through the design-of-experiments method. Structural and morphological characterization was performed, including the yield, thickness, and fiber arrangement of the scaffold. We evaluated the electrospinning process to enhance the manufacturing efficiency and reduce material loss. The results indicated that adjusting the voltage settings and polarity significantly increased the fiber yield from 8% to 94%. Variations in the process parameters also affected the scaffold thickness and homogeneity. The results demonstrate the complex relationship between the process parameters and provide valuable insights for optimizing electrospinning, particularly for the cost-effective and reproducible production of small tubular diameters. [ABSTRACT FROM AUTHOR]

Natural extracts, such as those from the residues of the Olea europaea industry, offer an opportunity for use due to their richness in antioxidant compounds. These compounds can be incorporated into porous polymeric devices with huge potential for tissue engineering such as bone, cardiovascular, osteogenesis, or neural applications using supercritical CO2. For this purpose, polymeric scaffolds of biodegradable poly(lactic-co-glycolic acid) (PLGA) and chitosan, generated in situ by foaming, were employed for the supercritical impregnation of ethanolic olive leaf extract (OLE). The influence of the presence of chitosan on porosity and interconnectivity in the scaffolds, both with and without impregnated extract, was studied. The scaffolds have been characterized by X-ray computed microtomography, scanning electron microscope, measurements of impregnated load, and antioxidant capacity. The expansion factor decreased as the chitosan content rose, which also occurred when OLE was used. Pore diameters varied, reducing from 0.19 mm in pure PLGA to 0.11 mm in the two experiments with the highest chitosan levels. The connectivity was analyzed, showing that in most instances, adding chitosan doubled the average number of connections, increasing it by a factor of 2.5. An experiment was also conducted to investigate the influence of key factors in the impregnation of the extract, such as pressure (10–30 MPa), temperature (308–328 K), and polymer ratio (1:1–9:1 PLGA/chitosan). Increased pressure facilitated increased OLE loading. The scaffolds were evaluated for antioxidant activity and demonstrated substantial oxidation inhibition (up to 82.5% under optimal conditions) and remarkable potential to combat oxidative stress-induced pathologies. [ABSTRACT FROM AUTHOR]

In this study, trivalent neodymium-doped silicate-based 13–93 bioactive glass scaffolds were prepared by the robocasting method using sol-gel-derived bioactive glass powders for tissue engineering applications. Sintered scaffolds were coated by borate-based 13-93B3 bioactive glass-containing polylactide-co-glycolide solution. The produced composite scaffolds' mechanical, morphological, and structural characteristics were thoroughly examined, as their in vitro bioactivity in cell culture media and simulated body fluid. Furthermore, the scaffolds' amoxicillin adsorption and release behavior was examined over time. The outcomes demonstrated that it was feasible to effectively create periodic, mesh-like-patterned robocast glass scaffolds utilizing Nd3+-doped sol-gel-derived bioactive glass powders. The scaffolds' compressive strengths ranged from 10.02 MPa to 18.6 MPa, with the PLGA-coated scaffolds exhibiting the highest strength values. All of the scaffolds that were submerged in simulated body fluid for 28 days showed hydroxyapatite formation. The presence of borate glass on the surface of the silicate-based glass scaffolds improved the hydroxyapatite formation ability. The quantity of drug adsorption for all types of scaffolds was measured to be between 4 and 9% whereas the cumulative drug release was in the range of 58 to 96%. Borate glass particle-containing PLGA coating enhanced the drug delivery behavior. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Taibah University Medical Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Lung cancer is the leading cause of death in cancer across the globe. To minimize these deaths, the replacement of traditional chemotherapy with novel strategies is significant. We have developed a nanotheranostic approach using silver nanoparticles for imaging and treatment. Silver nanoparticles (AgNPs) are fabricated by chemical reduction method. The formulation of AgNPs was confirmed by different characterization techniques like stability test, UV–Visible spectroscopy, Confocal Raman Spectroscopy, and Energy-Dispersive X-ray analysis. Further, AgNPs are coated with poly lactic-co-glycolic acid (PLGA) and then loaded with paclitaxel (Pac). Then the drug-loaded PLGA-coated AgNPs were characterized for size and zeta potential measurement by zetasizer, surface morphology study by atomic force microscopy, Fourier transform infrared spectroscopy, and release kinetics study. The imaging and anticancer properties of these nanoformulations are investigated using lung cancer cell lines. The results proved that the particles are in the nanometer range with smooth surface morphology. Moreover, the drug-loaded NPs showed a sustained release of the drug for a longer period of time. Further the formulations showed imaging property with greater anticancer efficacy. Thus, the results suggest the effective use of these nanoformulation in both lung cancer imaging and treatment using a simple and efficient approach. Schematic representation showing the mechanism of theranostic effect of PLGA coated Pac loaded silver nanoparticles. First silver nanoparticles were formulated then loaded with Pac and coated with PLGA. The formulated nanoparticles will enter into cells by the process of endocytosis and there it will release the drug and the silver. The drug will induce cytotoxicity whereas the silver nanoparticles will be used for imaging purpose. [ABSTRACT FROM AUTHOR]

Cannabinoids, such as ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are effective bioactive compounds that improve the quality of life of patients with certain chronic conditions. The copolymer poly(lactic-co-glycolic acid) (PLGA) has been used to encapsulate such compounds separately, providing pharmaceutical grade edible products with unique features. In this work, a variety of PLGA based nanoformulations that maintain the natural cannabinoid profile found in the plant (known as full-spectrum) are proposed and evaluated. Three different cannabis sources were used, representing the three most relevant cannabis chemotypes. PLGA nanocapsules loaded with different amounts of cannabinoids were prepared by nanoemulsion, and were then functionalized with three of the most common coating polymers: pectin, alginate and chitosan. In order to evaluate the suitability of the proposed formulations, all the synthesized nanocapsules were characterized, and their cannabinoid content, size, zeta-potential, morphology and in vitro bioaccessibility was determined. Regardless of the employed cannabis source, its load and the functionalization, high cannabinoid content PLGA nanocapsules with suitable particle size and zeta-potential were obtained. Study of nanocapsules' morphology and in vitro release assays in gastro-intestinal media suggested that high cannabis source load may compromise the structure of nanocapsules and their release properties, and hence, the use of lower content of cannabis source is recommended. [ABSTRACT FROM AUTHOR]

Resveratrol is an active ingredient in grapes with various biological and pharmacological activities, including anti-inflammatory, antioxidant, antiviral, phyto-estrogenic, antitumor, and anti-metastatic properties. However, its clinical applications are limited due to its photo-instability, low chemical stability, and poor bioavailability. This study aimed to address these limitations by developing resveratrol-loaded PLGA nanoparticles, modified with chitosan-folate (Res-PCF-NPs) and evaluating their anticancer effects against prostate cancer cells. The Res-PCF-NPs were characterized using dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), zeta potential (ξ–potential), and field emission scanning electron microscopy (FESEM) analyses. The biological experiments included resazurin assay and real-time PCR analysis performed to determine the cytotoxicity and apoptosis effects of Res-PCF-NPs on PC-3 prostate cancer cells. Additionally, the oxidant-antioxidant potential of the nanoparticles was examined by measuring the activity of antioxidant enzymes and conducting the DCF-DA assay. The resazurin assay demonstrated significant cytotoxic activity of Res-PCF-NPs against PC-3 cells, with an IC50 of 83 and 51 μg/mL at 24 and 48 h, respectively. Real-time PCR analysis confirmed the effect of Res-PCF-NPs on inducing cell death in PC-3 cells by modulating the expression of apoptosis-related genes. Also, our data suggests that the anticancer effect of Res-PCF-NPs is mediated through the induction of oxidative stress in PC-3 cells. Overall, our findings highlight the potential use of Res-PCF-NPs as an effective anticancer treatment for human prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: Decitabine is an inhibitor of DNA methyltransferase used to treat various types of leukemias. However, it is highly unstable in nature thereby needing an innovative intervention to harness its benefits. Thus, the study aimed to develop a stable nano-formulation of decitabine with improved pharmacokinetic characteristics. Method: In the present study, the Quality by Design approach was employed to systematically design and optimize decitabine-loaded nanoparticles. The nanoparticles were fabricated with emulsion solvent diffusion method and screened by 2K-1 fractional factorial design followed by Box-Behnken design to obtain nanoparticles with desirable characteristics. The optimized uncoated formulation was surface-modified to obtain PEGylated nanoparticles. The developed nanoparticles were further lyophilized using a suitable lyophilization cycle to obtain highly stable decitabine-loaded nanoparticles. The developed nanoformulations were assessed with in vitro and in vivo evaluation. Result: The lyophilized decitabine-loaded, uncoated and PEGylated nanoparticles exhibited a particle size of 194.5 nm and 177.9 nm and zeta potential of -32.9 mV and − 31.0 mV, respectively. Also, these exhibited a desirable encapsulation efficiency of 85.2% and 90.9%, respectively. The developed nanoformulations indicated a prolonged drug release over a period of 7 h. The in vivo study confirmed the improved pharmacokinetic parameters for drug-loaded nanoparticles in comparison to drug solution. Conclusion: The drug-loaded lyophilized nanoparticles were successfully developed and showcased superior quality attributes in both in vitro and in vivo assessments. This study thereby underscores the possible application of this nano-therapeutic system for leukemia treatment with implications for the broader landscape of nanomedicine and precision technology. [ABSTRACT FROM AUTHOR]