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Investigating the influence of the ambient chemical environment on molecular behaviors in liposomes is crucial for understanding and manipulating cellular vitality as well as the capabilities of lipid drug carriers in various environments. Here, we designed and synthesized a second harmonic generation (SHG) and fluorescence probe molecule called Pyr-Py+-N+ (PPN), which possesses membrane-targeting capability. We employed PPN to investigate the response of lipid vesicles composed of cardiolipin to the presence of exogenous salt. The kinetic behaviors, including the adsorption and embedding of PPN on the surface of small unilamellar vesicles (SUVs) composed of cardiolipin, were analyzed. The response of the SUVs to the addition of NaCl was also monitored. A rapid decrease in vesicle size can be evidenced through the rapid drop in SHG emission originating from PPN located on the vesicle surface. [ABSTRACT FROM AUTHOR]

The multifaceted chemo-immune resistance is the principal barrier to achieving cure in cancer patients. Identifying a target that is critically involved in chemo-immune-resistance represents an attractive strategy to improve cancer treatment. iRhom1 plays a role in cancer cell proliferation and its expression is negatively correlated with immune cell infiltration. Here we show that iRhom1 decreases chemotherapy sensitivity by regulating the MAPK14-HSP27 axis. In addition, iRhom1 inhibits the cytotoxic T-cell response by reducing the stability of ERAP1 protein and the ERAP1-mediated antigen processing and presentation. To facilitate the therapeutic translation of these findings, we develop a biodegradable nanocarrier that is effective in codelivery of iRhom pre-siRNA (pre-siiRhom) and chemotherapeutic drugs. This nanocarrier is effective in tumor targeting and penetration through both enhanced permeability and retention effect and CD44-mediated transcytosis in tumor endothelial cells as well as tumor cells. Inhibition of iRhom1 further facilitates tumor targeting and uptake through inhibition of CD44 cleavage. Co-delivery of pre-siiRhom and a chemotherapy agent leads to enhanced antitumor efficacy and activated tumor immune microenvironment in multiple cancer models in female mice. Targeting iRhom1 together with chemotherapy could represent a strategy to overcome chemo-immune resistance in cancer treatment.

Evidence supports that hyaluronic acid (HA) can promote tissue regeneration and reduce inflammation. This study aimed to assess the effects of a bilayered cellulose-coated HA scaffold on oral wound healing. A film-type 3% HA scaffold with bilayer cellulose coating was prepared and compared with an HA scaffold without coating. To evaluate cytocompatibility, human gingival fibroblasts were exposed to both scaffolds, and cell viability, flow cytometry, and scratch wound assays were performed. In addition, in vivo and ex vivo wound-healing assays were performed. Cytocompatibility tests showed no cytotoxicity for either HA scaffold. The scratch wound assay revealed a significant reduction in the open wound area in both HA scaffolds compared with that in the control (p < 0.05); however, no differences were observed between the scaffolds with and without cellulose coating. In vivo wound healing analysis showed significantly higher healing rates on day 3 in the HA scaffolds than in the control (p < 0.05), with no significant differences between the scaffolds. HA scaffolds with coating showed lower CD68 and higher vimentin expression than the control (p < 0.05), whereas HA scaffolds without coating did not. Ex vivo wound healing analysis revealed significantly higher re-epithelialization rates in both scaffolds than in the control (p < 0.05). Within the limits of this study, the HA scaffold with coating showed enhanced wound healing efficacy, indicating its potential for oral wound healing applications. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is a malignancy characterized by the proliferation of osteoblasts that predominantly affects pediatric and adolescent populations. At present, early detection of OS is significantly lacking, coupled with treatment challenges such as high recurrence rates, increased side effects, and the development of drug resistance. Therefore, developing new diagnostic and therapeutic modalities is clinically significant. Exosomes are naturally occurring nanoparticles found in the body that contain various materials, including DNA, RNA, and proteins. Owing to their numerous beneficial properties, including histocompatibility and in vivo stability, they can be useful as drug carriers. With the development of competitive endogenous non-coding RNA (ncRNA) networks, the role of ncRNA in OS cell control has been increasingly studied. This review provides a thorough summary of multiple potential biogenetic pathways of different ncRNAs in exosomes, including microRNAs, long ncRNAs, and circular RNAs. Moreover, the review highlights their effects on OS cells and their potential applications in the diagnosis, treatment, and control of OS drug resistance. The interplay between different types of ncRNAs, which collectively affect OS through the networks of competing endogenous ncRNAs, is the primary focus of this research. [ABSTRACT FROM AUTHOR]

Percutaneous coronary intervention (PCI) is currently the main method for treating coronary artery stenosis, but the incidence of restenosis after PCI is relatively high. Restenosis, the narrowing of blood vessels by more than 50% of the normal diameter after PCI, severely compromises the therapeutic efficacy. Therefore, preventing postinterventional restenosis is important. Vascular restenosis is mainly associated with endothelial injury, the inflammatory response, the proliferation and migration of vascular smooth muscle cells (VSMCs), excessive deposition of extracellular matrix (ECM) and intimal hyperplasia (IH) and is usually prevented by administering antiproliferative or anti-inflammatory drugs through drug-eluting stents (DESs); however, DESs can lead to uncontrolled drug release. In addition, as extracorporeal implants, they can cause inflammation and thrombosis, resulting in suboptimal treatment. Therefore, there is an urgent need for a drug carrier with controlled drug release and high biocompatibility for in vivo drug delivery to prevent restenosis. The development of nanotechnology has enabled the preparation of nanoparticle drug carriers with low toxicity, high drug loading, high biocompatibility, precise targeting, controlled drug release and excellent intracellular delivery ability. This review summarizes the advantages of nanoparticle drug carriers for treating vascular restenosis, as well as how nanoparticles have improved targeting, slowed the release of therapeutic agents, and prolonged circulation in vivo to prevent vascular restenosis more effectively. The overall purpose of this review is to present an overview of nanoparticle therapy for vascular restenosis. We expect these findings to provide insight into nanoparticle-based therapeutic approaches for vascular restenosis. [ABSTRACT FROM AUTHOR]

Ionogel has gained attention as a promising material for flexible electronic skin (e‐skin), due to its exceptional conductivity, compositional stability, and biocompatibility. Nevertheless, establishing a seamless interface between ionogel and human skin remains a significant challenge. This study presents the design and fabrication of a nanonet‐supported ionogel with a thickness of ≈16 µm, marking it the thinnest ionogel reported to date. This ultrathin ionogel exhibits remarkable toughness (5.51 MJ m−3), a broad strain range (0–375%), and impressive fatigue resistance, enduring over 3000 cycles. Additionally, it offers excellent water resistance and a high water vapor transmission rate (WVTR), supporting perspiration and enhancing skin breathability. Moreover, the ultrathin ionogel has potential as a carrier in transdermal drug delivery systems (TDDS), highlighting its suitability for biomedical applications. Wearable devices incorporating this ultrathin ionogel facilitate continuous, sensitive, and highly accurate monitoring of physiological signals, positioning it as a promising material for future flexible e‐skin material. [ABSTRACT FROM AUTHOR]

Purpose: Antibiotic coating for several medical devices has been carried out; however, there are only few studies about coating hernia meshes with antimicrobial substances. In this study we checked the capacity of different commercially available hernia meshes to act as drug carrier. Methods: The meshes were coated with gentamicin palmitate, chlorhexidine palmitic acid and chlorhexidine palmitate. The coating mass and subsequent in vitro delivery rate were evaluated for gentamicin palmitate by fluorescence polarization. For Chlorhexidine coated devices the coating mass was determined by weighing. The in vitro delivery rate was determined by UV absorption (255 nm). The interaction of each mesh to the different coating substances was observed by scanning electron microscopy. Results: 1. Certain uniformity was observed on the quantity of chlorhexidine coating the surface of each mesh used when compared with gentamicin palmitate coating. 2.We did not detect significant difference between the amounts of gentamicin palmitate released from each mesh. 3. The release of chlorhexidine palmitate and chlorhexidine palmitic acid from UltraPro™ and Mersilene™ were significantly higher (p<0.05) in comparison with the other two meshes. 4. The coating substances covered the surface of the fibers without damaging its structure. 5. The coating substances were distributed all along the fibers in all samples. Conclusions: We suggest the use of chlorhexidine palmitate and chlorhexidine palmitic acid, as well as gentamicin palmitate, for coating of hernia meshes aiming prevention of infections. Further investigation of the bactericidal effect of coated hernia meshes against biofilm form of S. aureus and other device-related infections is suggested. [ABSTRACT FROM AUTHOR]

To avoid the critical problems of effective drugs not being carried to their targeted cancers and their quantity and location not being sensed in situ, this work presents a completely new innovative strategy to achieve both smart cancer targeting (SCT) and super-sensitive sensing (SSS), where one drug carrier works for effective drug loading and release. Herein, malignant melanoma treatment is used as an example of reliable detection and effective therapy. We report two characteristic dumbbell-like nano-micelles and spherical-like nano-micelles of hyaluronan induced by the Eu3+/Tb3+ complexes for effective drug loading and release, respectively. These special Eu3+/Tb3+-loaded nano-micelles (marked as ENM and TNM) have strong and sharp red/green luminescence that can sensitively detect the malignant melanoma drug dacarbazine through changes in fluorescence intensity. Cytotoxicity experiments confirmed that both ENM and TNM are not toxic to normal cells at very high concentrations of 4 mM. However, when loaded with cancer drugs (D-ENM and D-ENM), they both killed cancer cells with more than 40% efficacy at this concentration. The in vivo experiments confirmed that D-ENM and D-TNM can effectively target cancer cells in tissue and effectively impede cancer growth. The detection limits of ENM and TNM in sensing cancer drugs can reach 0.456 μg/mL and 0.139 μg/mL, respectively. Therefore, the reported Eu3+/Tb3+-induced hyaluronan nano-micelles (ENM and TNM) are distinguished carriers of this cancer drug and excellent in situ sensors, and they have highly therapeutic effects with extremely low toxicity to normal cells. [ABSTRACT FROM AUTHOR]

Electrospun nanofibrous mats, consisting of chitosan (CS) and polyvinylpyrrolidone (PVP), were constructed with the addition of graphene oxide (GO) for enhancement of delivery of the 5-Fluorouracil (5-Fu) chemotherapy drug. Upon studying the range of GO concentrations in CS/PVP, the concentration of 0.2% w/v GO was chosen for inclusion in the drug delivery model. SEM showed bead-free, homogenous fibres within this construct. This construct also proved to be non-toxic to CaCo-2 cells over 24 and 48 h exposure. The construction of a drug delivery vehicle whereby 5-Fu was loaded with and without GO in various concentrations showed several interesting findings. The presence of CS/PVP was revealed through XPS, FTIR and Raman spectroscopies. FTIR was also imperative for the analysis of 5-Fu while Raman exclusively highlighted the presence of GO in the samples. In particular, a detailed analysis of the IR spectra recorded using two FTIR spectrometers, several options for determining the concentration of 5-Fu in composite fibre systems CS/PVP/5-Fu and GO/CS/PVP/5-Fu were demonstrated. By analysis of Raman spectra in the region of D and G bands, a linear dependence of ratios of integrated intensities of AD and AG on the intensity of host polymer band at 1425 cm−1 vs. GO content was found. Both methods, therefore, can be used for monitoring of GO content and 5-Fu release in studied complex systems. After incorporating the chemotherapy drug 5-Fu into the constructs, cell viability studies were also performed. This study demonstrated that GO/CS/PVP/5-Fu constructs have potential in chemotherapy drug delivery systems. [ABSTRACT FROM AUTHOR]

Biocompatibility is essential for drug delivery systems to ensure safety. Poly(lactic acid) (PLA) and its copolymers with glycolic acid and caprolactone, are known as safe biodegradable implants and carriers of drugs in clinical use. These polymers have been clinically used for the delivery of peptides, such as: LHRH, somatostatin and growth hormone. While the safety of PLA has been confirmed, the biocompatibility of PLA- based stereocomplexes with peptides has not been investigated. Stereocomplex is a complex formed by two molecules with opposite enantiomeric configuration. D-PLA consists of a chiral monomer thus can adopts a three dimensional structure which is a mirror image of a helix structure, therefore, complexes with insulin into a stereocomplex. In previous reports we demonstrated the formation of such stereocomplex. This study presents the safety evolution of a stereocomplex composed of the water soluble diblock copolymer of D-polylactic acid-co-polyetheylene glycol (DPLA-PEG) and Insulin, following subcutaneous administration of 17 mg sterecomoplex/mouse to Akita−/+ins2 mice. The mice were monitored for blood glucose levels and weight along the experiment, while growth necropsy and histopathology examination were done post sacrificing. Results demonstrated normal body weight gain with no pathological finding of an internal organ and no inflammatory signs at the injection site except of minimal macrophages, after 16 weeks following polymer administration. Hence, Stereocomplex of D-PLA-PEG/insulin is considered biocompatible with no adversity. [ABSTRACT FROM AUTHOR]

Phospholipid bilayers, which are a major component of cellular membranes and some drug delivery vehicles, can be in different states of order depending on the conformations of the hydrocarbon tails and their mutual arrangement. The important task of experimental characterization of phospholipid order is often addressed using Raman spectra of the C–H stretching bands. Such characterization uses some empirical relationships for apparent maxima in the spectra, although the origin of the sensitivity of the C–H band to phospholipid order and its model description remain unclear. Surely, a correct description of the sensitivity of the C–H band to phospholipid order is critical for its proper application. Here, we provide a description of the ordering sensitivity of the C–H stretching band using a polarized Raman experiment with hydrated aligned multibilayers of a saturated phospholipid. By this way, Raman contributions from symmetric and antisymmetric vibrations of CH2 were obtained in a model‐free manner. Experiments in a wide temperature range and the use of isotopic isolation helped us to consider separately the effects of conformational and lateral order of chains. The conformational sensitivity of the spectrum of antisymmetric vibrations was confirmed by DFT modeling. The outcomes of the study allowed us to provide recommendations for the use of the Raman spectrum of the C–H stretching band to characterize the conformational and lateral order of phospholipid‐containing materials. [ABSTRACT FROM AUTHOR]

Novel thiomer/nanoclay nanocomposites based on a thiomer and montmorillonite (MMT) were prepared in order to obtain a mucoadhesive material with controlled release properties for its potential use as drug carrier. The thiomer was synthesized by immobilization of L-cysteine in alginate mediated by carbodiimide reaction and further characterized by FT-IR and Ellman's reaction. Nanocomposites with growing concentrations of thiomer and MMT were prepared and analyzed by XRD, TGA and TEM. Rheological behavior of nanocomposite in contact with mucin and intestinal mucus were studied as in vitro and in situ mucoadhesion approach, showing until ∼10-fold increasing in the complex viscosity and ∼27-fold in elastic modulus when the amount of thiomer is increased. Higuchi and Korsmeyer-Peppas kinetic models were evaluated in order to study the release of deltamethrin from nanocomposite films. Release profiles showed a retard in the migration of the drug influenced by the amount of MMT (P < 0.05). Diffusion coefficient (D) showed a significant decrease (P < 0.0001) when concentration of MMT is increased reaching D = 4.18 × 10–7 m2 h–1, which resulted ∼7-fold lower in comparison with formulation without MMT. This hybrid nanocomposite can be projected as a potential mucoadhesive drug carrier with controlled release properties. [Display omitted] • Mucoadhesive nanocomposites based on a thiomer and montmorillonite was prepared. • Alginate was functionalized with L-cysteine showing 186.0 µmol –SH/g polymer. • XRD and TEM indicate intercalated forms for nanocomposites. • Mucoadhesion assay showed strong interaction between nanocomposite and mucin/mucus. • Higuchi and Korsmeyer-Peppas model satisfied release process with high R 2. • Nanocomposite present a controlled release depending the amount of MMT. [ABSTRACT FROM AUTHOR]

Introduction: Follicular delivery is one of the targeted drug delivery methods aiming to target the hair follicles. The accumulation and retention time of targeted drugs is enhanced when nanoparticles are used as drug carriers. Particle size is one of the important factors affecting the penetration and accumulation of particles in the hair follicles, and there is a controversy in different studies for the best particle size for follicular delivery. Mouse models are mostly used in clinical trials for dermal, transdermal, and follicular delivery studies. Also, it is essential to investigate the reliability of the results between human studies and mouse models. Methods: Curcumin-loaded nanostructured lipid carriers (NLCs), as a fluorescent agent, with three different particle size ranges were prepared using the hot homogenization method and applied topically on the mouse and human study groups. Biopsies were taken from applied areas on different days after using the formulation. The histopathology studies were done on the skin biopsies of both groups using confocal laser scanning microscopy (CLSM). We compared the confocal laser scanning microscope pictures of different groups, in terms of penetration and retention time of nanoparticles in human and mouse hair follicles. Results: The best particle size in both models was the 400 nm group but the penetration and accumulation of particles in human and mouse hair follicles were totally different even for the 400 nm group. In human studies, 400 nm particles showed good accumulation after seven days; this result can help to increase the formulation using intervals. Conclusion: The best particle size for human and mouse follicular drug delivery is around 400 nm and although mouse models are not completely suitable for follicular delivery studies, they can be used in some conditions as experimental models. [ABSTRACT FROM AUTHOR]

Both triptolide (TP) and cyclopamine (CPA) exhibit strong anticancer effects in vitro with adverse reactions and low bioavailabilities because of their water insolubility and poor liposolubility. The preparation of functional polymer materials into micelles not only improved the apparent solubility of the drug, changed the release behavior of the drug, but also made the drug targeted. All-atom molecular dynamics (MD) methods were used to simulate the states of both TP and CPA in PLA-PEG block copolymer micelles. MD results showed that TP and CPA were concentrated in the core layer of micelles formed by PLA-PEG block copolymers. The polymers PLLA-PEG-COOH were synthesized using HO-PEG-COOH and PLA and characterized by FTIR, 1H NMR, 13 C NMR, and gel chromatography. The dual drug-loaded polymeric micelle ((TP + CPA)-PM) was prepared by solvent evaporation, and the encapsulation rates of TP and CPA were 65.44% and 78.16% using the HPLC method, respectively. The polymer micelles were nearly spherical and did not aggregate under transmission electron microscopy (TEM), and the particle size was about 75.32 ± 0.20 nm through dynamic light scattering (DLS). (TP + CPA)-PM showed similar inhibitory effects to free drugs on A2780, A549, HepG2, and SKOV3 cells, which was proved by the MTT proliferation inhibition experiment, Hoechst33258 fluorescence staining experiment, and flow cytometry experiment. These results appeared to support the assumption that polymeric micelles encapsulation did not affect drug activity. PLA-PEG block copolymer may be a promising drug delivery vehicle for loading TP and CPA in antitumor therapy. [ABSTRACT FROM AUTHOR]

In the present investigation, we employed the hydrothermal approach for crafting mesoporous KIT-6 scaffolds and the post-impregnation technique for incorporating the drug. The concentration of berberine within the mesoporous channels of KIT-6 was assessed through UV–visible spectrophotometer. The results showed that the drug molecules were well integrated into the structure of KIT-6, displaying the material's 3D cubic mesoporous shape and its notable specific surface area of 1376 m2/g. The in vitro drug release profile was investigated in phosphate-buffered saline (pH = 6.8), and the findings point to the possibility of controlling the drug release quantity by loading the drug into the carrier. Using Vero cell lines, the toxicity of the drug-free and drug-loaded samples was examined and it was concluded that by adding berberine to the mesoporous matrix, the drug's toxicity was dramatically lowered. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a devastating kind of dementia that is becoming more common worldwide. Toxic amyloid-beta (Aβ) aggregates are the primary cause of AD onset and development. Superparamagnetic iron oxide nanoparticles (SPIONs) have received a lot of interest in AD therapy over the last decade because of their ability to redirect the Aβ fibrillation process and improve associated brain dysfunction. The potential diagnostic application of SPIONs in AD has dramatically increased this interest. Furthermore, surface-modified engineered SPIONs function as drug carriers to improve the efficacy of current therapies. Various preclinical and clinical studies on the role of SPIONs in AD pathology have produced encouraging results. However, due to their physicochemical properties (e.g., size, surface charge, and particle concentration) in the biological milieu, SPIONs may play the role of a preventive or accelerative agent in AD. Even though SPIONs are potential therapeutic and diagnostic options in AD, significant efforts are still needed to overcome the inconsistencies and safety concerns. This review evaluated the current understanding of how various SPIONs interact with AD models and explored the discrepancies in their efficacy and safety. [ABSTRACT FROM AUTHOR]

Observing the degradation rate of the bone fillers upon implantation enables us to predict the next stages of healing process. Strong luminescent property of the biocompatible carbon quantum dots accompanied by the high bioactivity of the 45S5 bioglass, bearing an antibiotic drug, can form reliable bone filler with detectable degradation rate via bioimaging. This study reported the preparation of fluorescent carbon quantum dots/45S5 (CQDs/45S5) nanohybrids via the chemical precipitation procedure for the first time. The pyrolysis of the citric acid was carried out to achieve the fluorescent N-doped CQDs with an average size of around 11 nm. The physicochemical and microstructural characteristics of the obtained materials were studied by XRD, FTIR and FESEM, respectively, Ultraviolet visible (UV–Vis) and photoluminescence (PL) spectroscopies were employed to investigate the features of the carbon dots as well as hybrid materials. The PL spectroscopy analysis indicated the in-vitro luminescent emission of the CQDs/45S5 nanohybrids compared to 45S5 bioglass. Around 22 μg of DOX could adhere to 1 mg of the nanohybrids after 12 h of contact, proposed that more quantity of particles were needed to adsorb higher amount of drug. The drug release study indicated a fast release pattern of DOX (90 %) during the first hours. The in-vitro bioactivity and biocompatibility results revealed the high capability of the BG/15 mL CQDs sample to deposit calcium phosphate with no toxic effects on the fibroblast cells. Consequently, the obtained nanohybrids could be promising trackable drug-vehicle candidates, as well as bone fillers, bone cements and implant coating materials. [ABSTRACT FROM AUTHOR]

In this study, MOF-74 nanocarriers were coated with sodium alginate (SALG) to enhance physicochemical properties and biocompatibility. Spectroscopic and microscopic analyses showed MOF-74 particle size below 100 nm. Zinc-based MOF-74 nanocarriers (Zn-MOF-74) were developed for doxorubicin (DOX) delivery, achieving high drug loading efficiency (DLE) and drug loading capacity (DLC) as measured by UV–visible spectrometry. Nanocarriers synthesized using zinc acetate (RA-MOF-74) achieved a DLE of 96.5% and a DLC of 19.6%, outperforming those prepared with zinc nitrate (RN-MOF-74) with a DLE of 88.8% and a DLC of 18.3%. Uncoated samples released cargo rapidly at pH 1.5 and significantly at pH 8. In contrast, SALG-coated samples showed reduced release at pH 1.5 and reached 54.2% release at pH 8 due to alginate's physicochemical properties. Drug release from DOX@RA-MOF-74/ALG was significantly slower and more sustained than from uncoated samples. This study demonstrates the potential of SALG-coated RA-MOF-74 as a controlled drug release system for biomedical applications. [ABSTRACT FROM AUTHOR]

Polyelectrolytes are used in different technology systems, such as reducing environmental pollution, producing lithium batteries, achieving better performance, and prolonging half-life. One of the vital applications of polyelectrolytes is in drug delivery systems as a drug carrier to reach the specific desired target organ and increase drug effectiveness. To find and reach the optimum complex of polyelectrolytes in the context of drug delivery systems, we used Luminescence spectroscopy, viscosimetry, and conductivity methods in different concentrations, pH, and temperatures to find the polyelectrolyte's behavior in cationic and anionic polymers besides copolymers. In this study, Polyallylamine P(AlAm), polyallylamine hydrochloride P(AlAm.HCl), polyvinyl sulfonic acid P(VSA), and copolymer (32:68) actual composition are investigated. The hydrophobicity of the polymer is prominent at higher pH with P(AlAm.HCl). A more hydrophilic polymer is produced by forming the NH3+ ions at lower pH. P(AlAm) hydrophobicity is determined at higher pH, and hydrophilicity happens at low pH. The temperature has now not affected the polymer's hydrophilicity and hydrophobicity. Increasing and lowering pH from 4.5 has not revealed a substantial P(VSA) change. The temperature and pH no longer affect the copolymer. We prepared complex formation of P(AlAm.HCl), P(AlAm), P(VSA), and copolymer with anionic surfactant sodium dodecylbenzene sulfonate (SDBS) in under and above critical micelle concentration (CMC) value. Excellent complexation is obtained among P(AlAm.HCl) and SDBS using Luminescence spectroscopy. Moreover, the viscosity behavior of P(AlAm.HCl) and P(AlAm) in pure water and 0.5 M NaCl solution is investigated. The polyelectrolyte properties of P(AlAm.HCl) are lots better than P(AlAm). That is confirmed using the Luminescence and conductivity method in different pH values. [ABSTRACT FROM AUTHOR]

Lanthanide luminescent materials have rapidly emerged as potential candidates in the fields of drug delivery and bioimaging. In this study a spherical composite material theory with uniform particle size, good biocompatibility, fluorescence emission performance and an efficient targeted drug delivery system was proposed. To achieve this, a facile ultrasonic atomization approach to synthesize sodium alginate-lanthanum (SA-La) cross-linked microspheres at room temperature was developed, and then they were loaded with doxorubicin (DOX), yielding DOX@SA-La for targeted liver cancer cell treatment. Fluorescence studies indicated that the SA-La microspheres exhibited excellent fluorescence properties with intense blue fluorescence emitted. Moreover, the ability of drug release in-vitro of the SA-La and Calcium alginate (SA-Ca) microspheres were proved by UV-visible spectrophotometry, and the drug release values of these two drug carriers were considerable. In addition, cytotoxicity tests via the CCK-8 assay revealed that the DOX@SA-La delivery system considerably inhibited hepatocellular carcinoma cells growth. Conclusively, the SA-La fluorescent microsphere drug carriers enables real-time anti-cancer efficacy observations and analyses, having promise as a potent therapeutic and diagnostic tool for liver cancer treatments and drug tracing in the tumors. [ABSTRACT FROM AUTHOR]

In recent decades, nanomedicine has attracted much attention at the forefront of nanotechnology, gaining great expectations in the biomedical sectors. Among various nanomaterials, silica nanoparticles-based drug delivery is considered effective owing to their physicochemical stability and biological compatibility. Surface grafting and chemical conversion techniques were used to create an amphoteric functional ligand known as amidoxime ligand (AL) modified mesoporous silica material (MS-AL NPs). With this technique, amidoxime ligand groups can be introduced in greater concentration to the silica surface without compromising its structure. The active surface allows for surface functionalization and integration of medicinal substances. They are widely employed in the bio-medical industry for diagnostics, target administration of drugs, bio-sensing, cellular absorption, and so on. The function of the produced MS-AL NPs as a regulated drug delivery system was studied utilizing doxorubicin (Dox) as a model anticancer drug. Using the MCF-7 cell line, the biocompatibility and cellular uptake characteristics were investigated. Considering all factors, the MS-AL NPs may be used as pH-responsive drug carriers in cancer treatment applications. [ABSTRACT FROM AUTHOR]

Exosomes are a kind of nanoscale membrane vesicles that can be secreted by many types of cells in both normal and pathological states and play a very important role in intercellular information exchange and transmission by transporting proteins, nucleic acids, lipids, and other biologically active substances to act on the receptor cells. Recent studies have shown that exosomes from some plants, animals, microorganisms, and other food sources can also be extracted like the structure of exosomes secreted by mammalian cells, which are named food-derived exosomes (FDEs) and can be absorbed by intestinal cells and further transported to other organs through blood circulation. With the advantages of high biocompatibility, low immunogenicity, low toxicity, high cargo capacity, and the ability to cross biological barriers, FDEs can be involved in a variety of applications such as immune response, cell migration, and tumor invasion, and have attracted a lot of attention as biotherapeutic agents and drug delivery carriers in the treatment of human diseases. This article reviews the classification, preparation characterization, physiological processes in the human body, biological functions, and application prospects of FDEs. It aims to provide a reference for the research and application of FDEs in disease treatment. [ABSTRACT FROM AUTHOR]

In combination therapy for tumors, combined components can play synergistic roles while leveraging their respective therapeutic advantages, but there are still some challenges in the development of nanomaterials for multimodal combination therapy for tumors. In this study, a novel targeted nanoparticle drug-delivery platform (HMPDA@Ce6/DOX@AMC) based on hollow mesoporous polydopamine (HMPDA) was designed for the synergistic treatment of tumors. HMPDA with a cavity structure was used to load the anticancer drug doxorubicin hydrochloride (DOX) and the photosensitizer chlorin e6 (Ce6). In the acidic tumor microenvironment, under the irradiation of a 660 nm laser, the carrier released Ce6 and DOX as a rapid response while producing cytotoxic reactive oxygen species (ROS). Next, the immunomodulator CpG, anticancer gene miR-145, and S6-aptamer were linked and named as AMC. The S6-aptamer was used for the accurate targeting of chemotherapy drugs to target cancer cells, and CpG was used for immunotherapy (IMT) by enhancing anti-tumor immune response. It was found that the average loading of DOX and Ce6 on the nanocarriers reached 242.65 mg g−1 and 90.86 mg g−1, respectively. Using the indicator 1,3-diphenylisobenzofuran (DPBF), it was detected that the prepared nanocarriers could produce ROS under the irradiation of a specific laser wavelength, and the yield was positively correlated with the irradiation time. Cytotoxicity experiments showed that the nanocarriers had an obvious inhibitory effect on 4T1 cells. The designed nanodrug-delivery system had a stronger tumor inhibition ability than single therapies under the combination of multiple therapies and is expected to achieve accurate targeting and enhanced treatment of early tumors. [ABSTRACT FROM AUTHOR]

Lung cancer has become the leading cause of cancer‐related deaths, surpassing all other forms of cancer. Among lung cancers, non‐small cell lung cancer (NSCLC) accounts for approximately 85% of cases. The use of tobacco, genetic traits, and radiation exposure are amongst the major reasons of lung cancer. The ongoing research in the medical field has considered the efficacy of nanocarriers in targeting various cancer cells. Among several biomaterials, lipid‐based nanocarriers have gained special attention due to their excellent compatibility, improved targeting efficacy, and encapsulation ability of diverse therapeutic agents. Phospholipids are naturally occurring amphiphilic moieties found in all living creatures. The presence of phospholipids in biomembrane aids the permeability of phospholipid‐based drug carrier. It can also facilitate targeting of therapeutic agents to cancer microenvironment without degrading the encapsulated drug. Phospholipids can be employed to develop conjugated nanocarriers and vesicular nanoformulation that can result in prolonged circulatory half‐life and controlled release of drugs. Phospholipids are also suitable biomaterials to attach a ligand for tissue‐specific targeting. Recent researches have reported effective targeting of chemotherapeutic agents, genes, and vaccines through phospholipid‐based nanocarriers to lung cancer cells. This review focuses on the rationality and applications of phospholipid‐based nanocarriers in lung cancer therapy. [ABSTRACT FROM AUTHOR]

Albumin, as a natural polymer, offers the advantages of non‐toxicity, degradability, and biocompatibility. It is widely used in formulating nanomedicines for cancer treatment. In this review, we introduce the methods and drawbacks of albumin nanoparticles when albumin is utilized as a drug carrier. We summarize the advantages of albumin nanoparticles in cancer treatment, discuss the surface modification of nanoparticles such as gold nanoparticles and magnetic nanoparticles by coating albumin as a functional group, and focus on the new properties of nanoparticles imparted by in vitro prefabrication of protein crowns. Additionally, we elaborate on the application of albumin in cancer vaccines. Finally, the challenges and future trends of albumin‐based nanodrugs in cancer therapy are presented. [ABSTRACT FROM AUTHOR]

ABSTRACT Metal–organic framework (MOF) is a porous material composed of metal ions/clusters and organic ligands. It has attracted much attention due to its high specific surface area, good biocompatibility, chemical modifiability, and diversity of components. Among many MOFs, zirconium‐based MOFs are particularly suitable for biological applications due to their optimal stability and low toxicity to hydrolysis. However, due to the weak coordination bonds between many metal clusters and organic ligands, most MOFs are prone to collapse in acidic environments, and the stability of MOFs as drug carriers cannot be guaranteed so that they cannot be widely used as oral drug carriers. This study synthesized the three MOFs using metal Zr ion clusters as the center and different nitrogen‐containing organic ligands, which are stable in gastric acid, namely, UiO‐66‐PDC, UiO‐66‐NH2, and UiO‐66‐NO2. The anionic drug loxoprofen (LOX) was loaded and characterized using scanning electron microscopy, infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and x‐ray diffraction. The adsorption and release behaviors of LOX and the three MOFs were studied from the molecular point of view by computer simulation. A series of behaviors and mechanisms of pH‐responsive nitrogen‐containing MOFs as oral drug carriers were further explored through rat pharmacokinetic experiments, the everted gut sac experiments, and intestinal absorption mechanism experiments. The experimental results show that there is a strong electrostatic interaction between anionic drug LOX and UiO‐66‐PDC under simulated gastric acid environment, which prolongs the half‐life of the drug, proving that LOX@UiO‐66‐PDC is a promising new oral drug delivery system. [ABSTRACT FROM AUTHOR]

Encapsulating biological and non-biological materials in lipid vesicles presents significant potential in both industrial and academic settings. When smaller than 100 nm, lipid vesicles and lipid nanoparticles are ideal vehicles for drug delivery, facilitating the delivery of payloads, improving pharmacokinetics, and reducing the off-target effects of therapeutics. When larger than 1 μm, vesicles are useful as model membranes for biophysical studies, as synthetic cell chassis, as bio-inspired supramolecular devices, and as the basis of protocells to explore the origin of life. As applications of lipid vesicles gain prominence in the fields of nanomedicine, biotechnology, and synthetic biology, there is a demand for advanced technologies for their controlled construction, with microfluidic methods at the forefront of these developments. Compared to conventional bulk methods, emerging microfluidic methods offer advantages such as precise size control, increased production throughput, high encapsulation efficiency, user-defined membrane properties (i.e., lipid composition, vesicular architecture, compartmentalisation, membrane asymmetry, etc.), and potential integration with lab-on-chip manipulation and analysis modules. We provide a review of microfluidic lipid vesicle generation technologies, focusing on recent advances and state-of-the-art techniques. Principal technologies are described, and key research milestones are highlighted. The advantages and limitations of each approach are evaluated, and challenges and opportunities for microfluidic engineering of lipid vesicles to underpin a new generation of therapeutics, vaccines, sensors, and bio-inspired technologies are presented. [ABSTRACT FROM AUTHOR]

Sodium alginate (AlgNa) is often used to prepare oral drug capsules, offering the advantages of facile carrier formation and pH sensitivity. However, these capsules suffer from high porosity, large pore size, and mechanical and physiological instabilities. Although the performance of AlgNa in oral drug carriers can be enhanced through hybridization with other substances, this results in increased complexity and additional preparation steps. To address this problem, organic–inorganic hybrid capsules are herein prepared via the one‐step incorporation of aminosilanes (3‐aminopropyltriethoxysilane and 3‐(2‐aminoethylamino)propyltrimethoxysilane) into AlgNa and evaluated as delivery vehicles for the sustained release of a model drug, diclofenac sodium. The hybrid capsules show elevated drug encapsulation efficiencies (up to 92.7%) and pH responsiveness and outperform pure alginate capsules, exhibiting contraction and low release rates (<10%) in a simulated stomach environment (pH 1.2) and swelling and sustained release (10 h) in a simulated intestinal environment (pH 7.4). The formation of siloxane bonds between the aminosilane molecules results in stronger and more compact capsule membranes contributing to sustained drug release. Thus, our results demonstrate the potential of the proposed capsules, fabricated using a simple ecofriendly method, as carriers for sustained drug release. [ABSTRACT FROM AUTHOR]

Metal‐organic framework materials (MOFs) are highly porous and are the subject of growing interest among scientists globally for their utilization in drug delivery. In this work, iron‐based metal‐organic frameworks (MOFs) MIL‐100(Fe) were synthesized by ultrasonic method and studied for the loading of the chloroquine phosphate (CQP). The CQP‐release behavior of the material was investigated in water media with various pH solutions of 1.2, 2, 4.5, and phosphate‐buffered saline (PBS) at temperatures of 25 °C to 45 °C. MIL‐100(Fe) material had a high surface area of up to 1080 m2/g and could completely release the CQP at a pH of 1.2 after 25 hours. At other pH conditions, the drug exhibited an initial rapid release, followed by a gradual slowdown, ultimately achieving complete release after 96 hours. The maximal loading capacity for the CQP by the MIL‐100(Fe) was determined to be approximately 30 % at the pH solution of 2 (stomach environment). The findings from the activity assessment against the K1 malaria parasite strain (P. falciparum) indicated that the concentration at which the active ingredient, when carried by the material, exhibited inhibition was 193 nM/L. The evaluation outcomes for acute toxicity of the drug carrier material revealed an LD50 value exceeding 5000 mg/kg (equivalent to 1500 mg of CQP base). In contrast, when using the active substance alone, acute toxicity resulted in an LD50 value of 675 mg/kg. [ABSTRACT FROM AUTHOR]

Nasal delivery is a non-invasive strategy for effective drug delivery. Nevertheless, in order to promote drug uptake by the nasal mucosa, it is fundamental to increase its residence time in the administration site. To this aim, nano-sized drug delivery systems are widely exploited. Within this context, the commercially available nanoemulsion for parenteral nutrition is a biocompatible, safe and clinically approved vehicle for drug delivery. Furthermore, the nanodroplet surface can be modified via a well-established protocol to graft Concavalin A, a lectin capable of improving the mucosal adhesion, by binding to the α-mannose and α-glucose residues of the mucosal glycocalyx. The obtained targeted formulation is able to induce haemagglutination, as opposite to non-modified nanoemulsion. Furthermore, the ConA grafting maintains the physicochemical properties of the nanodroplets (size~230 nm, Z < −35 mV) and does not interfere with the loading of the Rose Bengal fluorescent probe. Fluorescently labelled ConA grafted nanodroplets showed enhanced permeation and accumulation in ex vivo bovine nasal mucosa. This study is a proof of concept that Concanavalin A can be used to decorate the surface of nanodroplets, acting as a permeation promoter. [ABSTRACT FROM AUTHOR]

AbstractIschaemic stroke is a central nervous system disease with high morbidity, recurrence and mortality rates. Thrombolytic and neuroprotective therapies are the main therapeutic strategies for ischaemic stroke, however, the poor delivery efficiency of thrombolytic and neuroprotective drugs to the brain limits their clinical application. So far, the development of nanomedicine has brought opportunities for the above challenges, which can not only realise the effective accumulation of drugs in the target site, but also improve the pharmacokinetic behaviour of the drugs. Among the most rapidly developing nanoparticles, micelles gradually emerging as an effective strategy for ischaemic stroke treatment due to their own unique advantages. This review provided an overview of targeted and response-release micelles based on the physicochemical properties of the ischaemic stroke microenvironment, summarised the targeting strategies for delivering micellar formulations to the thrombus, blood-brain barrier, and brain parenchyma, and finally described the potentials and challenges of polymeric micelles in the treatment of ischaemic stroke. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) manifests as inflammation in the colon, rectum, and ileum, presenting a global health concern with increasing prevalence. Therefore, effective anti-inflammatory therapy stands as a promising strategy for the prevention and management of IBD. However, conventional nano drug delivery systems (NDDSs) for IBD face many challenges in targeting the intestine, such as physiological and pathological barriers, genetic variants, disease severity, and nutritional status, which often result in nonspecific tissue distribution and uncontrolled drug release. To address these limitations, stimulus-responsive NDDSs have received considerable attention in recent years due to their advantages in providing controlled release and enhanced targeting. This review provides an overview of the pathophysiological mechanisms underlying IBD and summarizes recent advancements in microenvironmental stimulus-responsive nanocarriers for IBD therapy. These carriers utilize physicochemical stimuli such as pH, reactive oxygen species, enzymes, and redox substances to deliver drugs for IBD treatment. Additionally, pivotal challenges in the future development and clinical translation of stimulus-responsive NDDSs are emphasized. By offering insights into the development and optimization of stimulus-responsive drug delivery nanoplatforms, this review aims to facilitate their application in treating IBD. This review highlights recent advancements in stimulus-responsive nano drug delivery systems (NDDSs) for the treatment of inflammatory bowel disease (IBD). These innovative nanoplatforms respond to specific environmental triggers, such as pH reactive oxygen species, enzymes, and redox substances, to release drugs directly at the inflammation site. By summarizing the latest research, our work underscores the potential of these technologies to improve drug targeting and efficacy, offering new directions for IBD therapy. This review is significant as it provides a comprehensive overview for researchers and clinicians, facilitating the development of more effective treatments for IBD and other chronic inflammatory diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Sinapine is a natural polyphenol from the cruciferous plant family that has anti-aging effects but is low in bioavailability. To improve the bioavailability and therapeutic effect of sinapine, sinapine-crosslinked dual-protein-based hydrogels were prepared using soy protein isolate as a cross-linking agent. The preparation conditions were optimized by single-factor experiments, and the optimal ratios were obtained as follows: the concentration of sinapine was 300 μg/mL; the water–oil ratio was 1:3. The encapsulation rate was greater than 95%, and the drug loading capacity was 3.5 mg/g. In vitro, digestion experiments showed that the dual-protein-based hydrogels as a drug carrier stabilized the release of sinapine and improved the bioavailability of sinapine by 19.3%. The IC50 of DPPH antioxidants was 25 μg/mL as determined by in vitro digestion, and the antioxidant capacity of ABTS was about 20% higher than that of glutaraldehyde control. This is due to the addition of sinapine to enhance the antioxidant properties of the system. It can be seen that the developed hydrogels have potential applications in related fields, such as food nutrition fortification and drug delivery. [ABSTRACT FROM AUTHOR]

Cationic cetyltrimethylammonium (CTAB) is an effective and common intercalator for interlayered modification in layered materials, while its biotoxicity remains an issue. To improve biosafety and biocompatibility of the drug delivery system, the nontoxic chitosan (CS) was introduced into CTAB‐modified kanemite (Ka‐CTAB). Accordingly, the obtained Ka‐CTAB/CS was further used as a drug carrier of methotrexate (MTX). Various characterizations were employed to investigate the drug delivery system based on the Ka‐CTAB/CS. Results revealed that the loading capacity of the drug delivery system based on the Ka‐CTAB/CS for MTX was about 13.47%, and the drug delivery system exhibited slow and sustained release of drugs either in phosphate buffer solution (pH = 7.4) or in HCl solution (pH = 1.35). The introduction of CS in Ka‐CTAB/CS not only replaced a part of CTAB in composition but also prevented CTAB molecules falling off the carrier during the drug‐releasing process. In the methyl orange dye assay, the concentration of free CTAB shed from Ka‐CTAB/CS was as low as 8.09 × 10−7 mol/L after 24 h. In an in vitro cell viability assay using HepG2 cells, Ka‐CTAB/CS also exhibited lower cytotoxicity compared to previous Ka‐CTAB. [ABSTRACT FROM AUTHOR]

The blood‐brain barrier (BBB) poses a significant challenge in delivering therapeutic agents for brain diseases due to its high selectivity against foreign substances. This limitation greatly hampers the effectiveness of conventional chemotherapeutic drugs in treating brain cancers. In response, lipid‐based nanoparticles (LNPs) have emerged as a promising approach, offering opportunities for targeted drug delivery by conjugating targeting ligands onto their surface. This review provides a comprehensive overview of recent advancements in utilizing LNPs to traverse the BBB for enhanced transport of bioactive compounds into the brain, specifically for cancer treatments. Beginning with an exploration of the biological structure and functions of the BBB and the blood‐brain tumor barrier (BBTB), the review highlights the advantages presented by LNPs. Subsequently, it delves into strategies for surface modification of nanoparticles to enhance BBB targeting and improve efficacy in brain cancer treatment. Finally, the review offers insights into future prospects for designing the next generation of LNPs. The review presented herein aims to contribute to the ongoing efforts in overcoming the challenges associated with BBB penetration, ultimately advancing therapeutic strategies for brain cancer and other neurological disorders. [ABSTRACT FROM AUTHOR]

The gut communicates with the brain in a variety of ways known as the gut–brain axis (GBA), which is known to affect neurophysiological functions as well as neuronal disorders. Exosomes capable of passing through the blood–brain-barrier (BBB) have received attention as a mediator of gut–brain signaling and drug delivery vehicles. In conventional well plate-based experiments, it is difficult to observe the exosome movement in real time. Here, we developed a microfluidic-based GBA chip for co-culturing gut epithelial cells and neuronal cells and simultaneously observing exosome transport. The GBA-chip is aimed to mimic the in vivo situation of convective flow in blood vessels and convective and diffusive transport in the tissue interstitium. Here, fluorescence-labeled exosome was produced by transfection of HEK-293T cells with CD63-GFP plasmid. We observed in real time the secretion of CD63-GFP-exosomes by the transfected HEK-293T cells in the chip, and transport of the exosomes to neuronal cells and analyzed the dynamics of GFP-exosome movement. Our model is expected to enhance understanding of the roles of exosome in GBA. [ABSTRACT FROM AUTHOR]

PVA‐κcarrageenan (κCar) gel is widely used in the pharmaceutical field for transdermal drug delivery, enhancing drug stability and bioavailability. This study aims to modify PVA‐κCar gel by introducing tannic acid. Lidocaine was used as a model drug for incorporation into the novel gel. The PVA‐κCar matrix was mixed with tannic acid prior to freeze– thaw cycle to create a gel composite. The physicochemical features of this gel were evaluated using FTIR, XRD, thermal analysis, and SEM. The presence of tannic acid has reduced the thermal stability of PVA‐κCar from 84 to around 70 °C. The gel content of tannic acid‐modified PVA‐κCar was 34.6% (A) and 52.1% (B). The addition of tannic acid substantially increased gel viscosity. Cytotoxicity analysis showed that tannic acid‐modified PVA‐κCar gel did not affect the viability of HCT colon cancer cells. The encapsulation efficiency of lidocaine in tannic acid‐modified PVA‐κCar was 13 ± 0.2% (A) and 12 ± 0.5% (B), while the drug loading was 0.96 ± 0.01 (A) and 0.91 ± 0.02 (B). In vitro release of lidocaine from the modified PVA‐κCar exhibited a sustained release mechanism in phosphate‐buffered saline solution. These findings indicate that the gel possesses advantageous characteristics as a drug carrier. [ABSTRACT FROM AUTHOR]

Antibiotic‐resistant bacteria have rapidly emerged in recent years as a result of irrational use of antibiotics. The development of drug carriers that can enhance antibacterial activity of antibiotics can potentially overcome antibiotic resistance and hence has practical significance. This study addresses this need by integrating amine‐functionalized magnetic nanoparticles (AMNPs) into hydrogel microbeads composed of sodium alginate (SA) and xanthan gum (XG) for delivery of levofloxacin (LVX). Characterization of the microbeads confirmed successful AMNP–polymer interactions and demonstrated a porous structure inside the microbeads. The microbeads demonstrated pH‐sensitive drug release behavior, enabling prolonged drug release. The drug encapsulation efficiency in the hydrogel microbeads was higher after AMNP incorporation, indicating the potential roles played by the porous network and by AMNP‐LVX interactions during drug loading. The microbeads adhered to first‐order, Higuchi, and Korsmeyer‐Peppas kinetic models, suggesting that a combination of diffusion and polymer relaxation mechanisms is involved in drug release. Along with the fact that the AMNP‐incorporated microbeads exhibited enhanced antibacterial activity against various bacterial strains, our microbeads warrant further development and optimization as drug carriers for antibacterial applications. [ABSTRACT FROM AUTHOR]

Recently, the anti-tumor effects of cannabis extract on various cancers have attracted the attention of researchers. Here, we report a nanoemulsion (NE) composition designed to enhance the delivery of two active components in cannabis extracts (∆9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD)) in an animal model of glioblastoma. The efficacy of the NE containing the two drugs (NED) was compared with the bulk drugs and carrier (NE without the drugs) using the C6 tumor model in rats. Hemocompatibility factors (RBC, MCV, MCH, MCHC, RDW, PPP, PT and PTT) were studied to determine the potential in vivo toxicity of NED. The optimized NED with mean ± SD diameter 29 ± 6 nm was obtained. It was shown that by administering the drugs in the form of NED, the hemocompatibility increased. Cytotoxicity studies indicated that the NE without the active components (i.e. mixture of surfactants and oil) was the most cytotoxic group, while the bulk group had no toxicity. From the in vivo MRI and survival studies, the NED group had maximum efficacy (with ~4 times smaller tumor volume on day 7 of treatment, compared with the control. Also, survival time of the control, bulk drug, NE and NED were 9, 4, 12.5 and 51 days, respectively) with no important adverse effects. In conclusion, the NE containing cannabis extract could be introduced as an effective treatment in reducing brain glioblastoma tumor progression. [ABSTRACT FROM AUTHOR]

The study examined the efficacy of additives in preventing the crystallization of functional ingredients during the spray-drying process. Spray-drying of a hydrophobic drug from alcohol in the presence of a hydrophilic carrier-forming agent was utilized as a representative scenario, which frequently leads to the crystallization of the main drug component induced by the drying process. Ibuprofen (IBP) and its four congeners were employed as representatives of readily crystallizable hydrophobic pharmaceutical compounds. Disaccharides were intentionally employed as components of the drug carrier to create conditions conducive to crystallization. Ten materials, including the IBP congeners, were investigated for their anti-crystallization properties. The findings indicated that additives with a hydrophobic moiety similar to that of IBP and a carboxylic acid salt moiety effectively prevented IBP and its congeners from crystallizing when the additive content was ≥0.2 g/g-drug during spray-drying and storage at 30 °C over silica gel. [ABSTRACT FROM AUTHOR]

Exosomes are small nanovesicles that are produced through the fusion of multiple veins and plasma membranes, then escaping into adjacent body fluids. Considerable attention has been paid to them due to their potential as delivery vehicles for drugs. Exosomes play a key role in many physiological processes that occur both in healthy and ill states. The production of exosomes depends on the state of the disease, but the disease itself often serves the opposite function by promoting more cell damage and stress. Traditional drug delivery methods often face limitations in terms of specificity, targeted delivery and drug release kinetics. Exosomes have emerged as promising candidates for drug delivery due to their natural ability to selectively deliver cargoes to recipient cells. Exosomes are taken up through various mechanisms, including endocytosis and fusion with target cells. They can encapsulate poorly soluble drugs, enhancing their bioavailability and improving their therapeutic efficacy. Exosomes inspired Lipid Nanovesicles (Exo-LNVs) have shown promising results as drug delivery vehicles. Exosomes have considerable potential as sophisticated vehicle for the delivery of targeted drugs and genes due to their unique characteristics, including inherent stability, minimal immunity and exceptional ability to penetrate tissues and cells. Therapeutic interventions have the capacity to increase effectiveness, reduce side effects and increase patient compliance. Exosomes have the ability to transport various therapeutic by encapsulating different substrates such as nucleic acids, proteins and small molecules. Recent advancements in exosome-inspired lipid nanovesicles have opened up new possibilities for cell-specific drug delivery. These nanovesicles mimic the composition and structure of exosomes, which are naturally occurring extracellular vesicles released by cells. By incorporating therapeutic agents into the lipid nanovesicles, they can effectively target and deliver drugs to specific cells of interest. This review article aims to summarize the current literature on Exo-LNVs and discuss their potential as drug delivery vehicles. A systematic search was conducted to identify relevant studies and relevant data were extracted and analyzed. The review covers various aspects of Exo-LNVs, including their composition, preparation methods and applications in various disease conditions. [ABSTRACT FROM AUTHOR]

In this study, glutathione (GSH)-responsive magnetic mesoporous silica nanoparticles grafted by disulfide organosilicon (SMNPs) were synthesized, characterized, and evaluated as controlled drug carriers. The nanoparticles exhibited consistent dispersion, considerable drug-loading capacity, and high saturation magnetization. Importantly, they demonstrated the ability to release doxorubicin (DOX) by up to 43% in a reducing tumor microenvironment, highlighting their potential for targeted therapy. In addition, the SMNPs displayed favorable biocompatibility, making them suitable for biomedical applications. Most notably, the SMNPs loaded with DOX effectively killed both HepG2 and HeLa cancer cells, while also showing efficient cellular uptake in HeLa cells. These findings suggest that SMNPs are a promising platform for magnetic-targeted and GSH-responsive delivery of therapeutic agents. [ABSTRACT FROM AUTHOR]

This systematic review examines the landscape of extracellular vesicle (EV)‐related clinical trials to elucidate the field's trends in clinical applications and EV‐related methodologies, with an additional focus on the acknowledgement of EV subpopulations. By analysing data from public reporting repositories, we catalogued 471 EV‐related clinical trials to date, with indications for over 200 diseases. Diagnostics and companion diagnostics represented the bulk of EV‐related clinical trials with cancer being the most frequent application. EV‐related therapeutics trials mainly utilized mesenchymal stromal cell (MSC) EVs and were most frequently used for treatment of respiratory illnesses. Ultracentrifugation and RNA‐sequencing were the most common isolation and characterization techniques; however, methodology for each was not frequently reported in study records. Most of the reported characterization relied on bulk characterization of EV isolates, with only 11% utilizing EV subpopulations in their experimental design. While this may be connected to a lack of available techniques suitable for clinical implementation, it also highlights the opportunity for use of EV subpopulations to improve translational efforts. As academic research identifies more chemically distinct subpopulations and technologies for their enrichment, we forecast to more refined EV trials in the near future. This review emphasizes the need for meticulous methodological reporting and consideration of EV subpopulations to enhance the translational success of EV‐based interventions, pointing towards a paradigm shift in personalized medicine. [ABSTRACT FROM AUTHOR]

Exosomes are cell-derived, membrane-surrounded particles that deliver bioactive molecules to various cells. Due to their small size, low immunogenicity, extended blood circulation, and involvement in cellular communication, they hold potential as effective drug carriers. Exosomes are present in various biological fluids, including mare's milk, a traditional drink in Central Asia. This study aims to compare exosome isolation methodologies and determine the stability of mare's milk-derived exosomes as potential therapeutic carriers. Three extraction methods—immunoprecipitation, size exclusion chromatography, and total exosome isolation—were compared in terms of exosome characteristics, purity, and content. The isolated exosomes were then loaded with quercetin, and their ability to increase its bioavailability was tested in vitro and in vivo. Total exosome isolation was identified as the most efficient method for producing high-quality exosomes. These exosomes were loaded with quercetin and compared to free quercetin and exosomes alone. Exosomes loaded with 80 µM quercetin significantly restored β-galactosidase activity and cellular viability in doxorubicin-treated cells, exhibiting similar potency to 160 µM free quercetin. In aged model animals, treatment with quercetin-loaded exosomes resulted in significantly less acute and subacute damage to the myocardium, kidneys, and liver compared to untreated control animals. This study provides a proof-of-concept that mare's milk-derived exosomes can be effectively absorbed by cells and animal tissues, supporting their potential use as drug carriers. [ABSTRACT FROM AUTHOR]

Cell membrane-derived liposomes, termed Memposomes, serve as promising carriers for drug delivery due to their ability to closely mimic cells and efficiently target specific cells. Liposomes derived from cancer cell membranes, in particular, exhibit homologous targeting capabilities, making them potential candidates for cancer-specific drug delivery. However, the underlying mechanisms and specific proteins responsible for this homologous targeting phenomenon remain debated. This study focuses on the role of E-cadherin, a cell adhesion molecule implicated in homophilic adhesion, in influencing the homologous targeting ability of Memposomes derived from cancer cell membranes. E-cadherin expression patterns were assessed in various cell lines, categorizing them into E-cadherin-positive and -negative groups. Memposomes were produced for each group, and their targeting tendencies were evaluated. This study confirmed that E-cadherin expression significantly influenced the homologous targeting ability of the Memposomes. The cell lines with higher E-cadherin expression levels exhibited a more pronounced homologous targeting effect. This research demonstrates that cell adhesion molecules, particularly E-cadherin involved in homophilic adhesion, play a pivotal role in influencing the cell targeting ability of Memposomes. This study further validates the stability, safety, and purity of Memposomes, emphasizing their potential as effective drug delivery vehicles for the development of cell-specific therapies. [ABSTRACT FROM AUTHOR]

In this study we have developed a high-dose dry powder inhaler formulation of indomethacin using a novel approach to carrier-based formulations. Specifically, larger drug particles serve as the carrier for the smaller micronized drug particles, such that an inhaled dose is combined with an oral dose. To study this system, the aerosol performance of a standard indomethacin–lactose formulation was compared to carrier-free micronized indomethacin and a drug-as-carrier formulation (a micronized indomethacin–coarse indomethacin blend). Indomethacin with lactose showed a very poor aerosol performance, indicating high adhesion between the drug and carrier. The performance of the carrier-free micronized drug was significantly better, indicating low cohesion. Coarse drug particles as a carrier allowed improved powder flow and aerosol performance while also providing a potential secondary route of absorption of indomethacin, namely oral. An optimal formulation ratio of 1:1 (w/w) fine indomethacin–coarse indomethacin was developed in this study. [ABSTRACT FROM AUTHOR]

Hyaluronic acid (HA) is a naturally occurring polysaccharide found in the extracellular matrix with broad applications in disease treatment. HA possesses good biocompatibility, biodegradability, and the ability to interact with various cell surface receptors. Its wide range of molecular weights and modifiable chemical groups make it an effective drug carrier for drug delivery. Additionally, the overexpression of specific receptors for HA on cell surfaces in many disease states enhances the accumulation of drugs at pathological sites through receptor binding. In this review, the modification of HA with drugs, major receptor proteins, and the latest advances in receptor‐targeted nano drug delivery systems (DDS) for the treatment of tumors and inflammatory diseases are summarized. Furthermore, the functions of HA with varying molecular weights of HA in vivo and the selection of drug delivery methods for different diseases are discussed. [ABSTRACT FROM AUTHOR]

Acoustic trap, using ultrasound interference to ensnare bioparticles, has emerged as a versatile tool for life sciences due to its non-invasive nature. Bolstered by magnetic resonance imaging's advances in sensing acoustic interference and tracking drug carriers (e.g., microbubble), acoustic trap holds promise for increasing MRI-guided microbubbles (MBs) accumulation in target microvessels, improving drug carrier concentration. However, accurate trap generation remains challenging due to complex ultrasound propagation in tissues. Moreover, the MBs' short lifetime demands high computation efficiency for trap position adjustments based on real-time MRI-guided carrier monitoring. To this end, we propose a machine learning-based model to modulate the transducer array. Our model delivers accurate prediction of both time-of-flight (ToF) and pressure amplitude, achieving low average prediction errors for ToF (−0.45 µs to 0.67 µs, with only a few isolated outliers) and amplitude (−0.34% to 1.75%). Compared with the existing methods, our model enables rapid prediction (<10 ms), achieving a four-order of magnitude improvement in computational efficiency. Validation results based on different transducer sizes and penetration depths support the model's adaptability and potential for future ultrasound treatments. [ABSTRACT FROM AUTHOR]

The identification of suitable nanocarriers for drug delivery has been a constant area of research and development. Two-dimensional nanomaterials based on graphene have been presented and proven as drug carriers in this instance. In this study, we employed calculations from density functional theory to examine the electronic and adsorption properties of the commonly administered anticancer medication hydroxyurea (HU) on armchair BN graphene nanoribbons with and without vacancy defects. The band gap of the structures, both with and without the presence of an anticancer drug, exhibits semiconductor behavior, with the exception of ABNNR which initially exhibits insulator behavior with a 6.009 eV energy gap, but upon interaction with the HU molecule, the energy disparity diminished to 4.72 eV. With an Eads = − 1.079 eV, the adsorption energy of the HU drug molecule on ABNNR-VN is significantly greater than that of the other complex structures. Based on the computed structural and electronic characteristics, it has been determined that HU/ABNNR-VN exhibits a greater propensity for HU molecule adsorption in comparison to alternative structures. [ABSTRACT FROM AUTHOR]