Therapeutic delivery最新文献

Background: Type 2 diabetes mellitus (T2DM) is the most devastating disease and it necessitates therapeutic intervention for its effective management. Human Glucagon-like peptide-1 (HuGLP-1) is the potential candidate in the treatment of T2DM; however, it limits its utilization owing to its solubility and stability issues.

Aims: The current investigation aims to develop HuGLP-1-loaded bilosomes as a novel strategy for managing T2DM.

Materials and methods: The HuGLP-1-loaded bilosomes were developed and characterized for its size, polydispersity index, surface charge, entrapment efficiency, morphology, drug release, and stability studies. The hypoglycemic potential and histopathology were studied using streptozotocin-induced diabetic rats.

Results: Bilosomes were successfully developed with size of 197.96 ± 0.61 nm, polydispersity index 0.191 ± 0.01 and surface charge of -27.63 ± 1.02 mV. The in vitro release of HuGLP-1-loaded bilosomes showed sustained release profile of HuGLP-1 extending over 24-h period, in compared to plain HuGLP-1 solution, and follows Weibull release kinetics model. The HuGLP-1-loaded bilosomes revealed significant hypoglycemic effects in comparison to both oral and subcutaneous HuGLP-1 solutions. Histopathological evaluations revealed that HuGLP-1-loaded bilosomes showed promising improvement in histology of liver, kidney, and intestines.

Conclusion: The HuGLP-1-loaded bilosomes were found to be potential therapeutic approach for the effective management of T2DM.

Chronic oral inflammatory diseases such as pulpitis, periodontitis, and peri-implantitis pose significant clinical challenges, often resulting in irreversible tissue loss despite the application of current therapies. Specialized pro-resolving mediators (SPMs) offer a novel therapeutic paradigm by actively promoting the resolution of inflammation and tissue regeneration without compromising host defense. However, the clinical translation of SPMs is hindered by their rapid degradation, low bioavailability, and poor localization to inflamed tissues. Smart biomaterial-based delivery systems, particularly stimuli-responsive hydrogels, have emerged as promising platforms to overcome these barriers. These systems enable controlled, localized, and environment-triggered release of SPMs, enhancing their stability and therapeutic efficacy. Preclinical studies in models of oral inflammation demonstrate that hydrogel-mediated SPM delivery not only resolves inflammation but also preserves tissue structure and promotes regeneration. Future strategies will focus on optimizing dosing protocols, ensuring long-term bioactivity, and addressing regulatory and manufacturing challenges to enable clinical adoption. By enhancing the delivery and sustained bioactivity of SPMs, biomaterial-based strategies have the potential to fundamentally transform the management of oral inflammatory diseases and advance regenerative dental therapies.

Aims: Breast cancer (BC) is the most prevalent cancer diagnosed globally. Olaparib (OLA) BCS-IV class drug, is an inhibitor of the poly(ADP-ribose)polymerase enzyme. Due to its restricted absorption, an escalation in dosage and frequency is necessary to attain therapeutic efficacy, which may lead to potential toxicity in patients. In this study, nanostructured lipid carriers (NLCs) were prepared to mitigate OLA's side effects by reducing the dose without compromising efficacy.

Materials and methods: OLA-NLCs were formulated, and a Design of Experiments optimization technique was utilized to assess essential formulation parameters systematically. Investigations were conducted on particle size, polydispersity index, zeta potential, encapsulation efficiency, release, and stability assessments. The impact of NLCs was evaluated on MCF-7 and MDA-MB-231 cell lines.

Results: OLA-NLCs were evaluated for particle size (134.0 ± 2.56 nm), PDI (0.32 ± 0.01), ZP (-37.7 ± 0.89 mV), and EE (97.28 ± 1.48%). The in-vitro release profile of OLA-NLCs showed a sustained release pattern for 72 h. OLA-NLCs showed a concentration-dependent effect on cell viability for 24 h and 72 h. The uptake of OLA-NLCs was almost 1.75 and 3.69 times higher for MCF-7 and MDA-MB-231, respectively, compared to free-OLA. OLA-NLCs induced more cancer cell apoptosis than free-OLA.

Conclusions: Our data suggest OLA-NLCs may be a practical approach for BC treatment.

Aim: This study focuses on the development of a drug delivery system through microencapsulation of salbutamol sulfate using biocompatible and biodegradable polymers poly(D,L-lactic acid) and poly(e-caprolactone) (PDLLA 60: PCL 40% w/w).

Methods: We employed an oil-in-water (o/w) emulsification technique and Span 80-Tween 80 mixture as an emulsifier to generate PDLLA/PCL microcapsules. The dissolution test was conducted in acid and base medium to demonstrate drug release.

Results: The highest average encapsulation efficiency of salbutamol sulfate was 83.21%, while the dissolution test of salbutamol sulfate microcapsules coated with polyblend PDLLA/PCL was carried out in-vitro. They released 32.21% of the drug in HCl solution pH 1.2 and 17.18% in phosphate buffer solution pH 7.4. The mechanism of drug release from the polymer matrix occured via controlled diffusion, which was able to sustain the drug release.

Conclusion: Although the total drug release is below expectations, the findings indicate that this system has potential to enhance patient compliance and reduce adverse effects by improving the therapeutic effect of salbutamol sulfate through oral administration.

Introduction: Breast cancer remains one of the leading causes of cancer-related deaths among women worldwide. Despite the availability of chemotherapeutics, such as doxorubicin, treatment efficacy, is often hampered by multidrug resistance, largely driven by efflux transporters like P-glycoprotein.

Aim & objectives: This study aimed to develop and evaluate a targeted liposomal system for the co-delivery of doxorubicin and quercetin to overcome multidrug resistance in breast cancer cells. The objective was to enhance therapeutic efficacy while minimizing systemic toxicity.

Method: Liposomes were prepared using the thin-film hydration method and optimized via Box-Behnken Design. Two formulations, doxorubicin and quercetin liposomes (DOX-QCT-LIPO) and Trastuzumab conjugated (TmAb-DOX-QCT-LIPO), were characterized for vesicle size, PDI, and entrapment efficiency. Their cytotoxicity (MTT assay) and cellular uptake (FACS) were tested in MCF-7 and MCF-7/ADR cell lines.

Results: Optimized formulations exhibited nanoscale size, uniform distribution, and high drug encapsulation. Tmab-DOX-QCT-LIPO showed significantly enhanced cytotoxicity and uptake in MDR breast cancer cells compared to free DOX and non-targeted liposomes, indicating effective bypass of efflux mechanisms via HER2-mediated endocytosis.

Conclusion: TmAb-DOX-QCT-LIPO demonstrated superior anticancer potential by integrating dual-drug loading, P-gp inhibition, and HER2-targeted uptake, offering a promising therapeutic strategy against MDR breast cancer.

Chimeric antigen receptor (CAR) T-cell therapy is a revolutionary cancer treatment, but it has severe side effects. Extracellular vesicles (EVs), nanovesicles released by CAR T cells, known as CAR T-cell-derived EVs (CAR-EVs), are a potential alternative owing to their role in intercellular communication. This review comprehensively explores the clinical potential of CAR-EVs for cancer therapy, starting with their biogenesis and cargo, which include unique therapeutic molecules. It reviews the mechanisms underlying CAR-EV-mediated anticancer effects and presents preclinical evidence demonstrating efficacy across various cancers, including hematological malignancies and solid tumors. The review further discusses preclinical data and advantages over existing CAR T-cell therapies, emphasizing the need for future clinical studies to assess the safety and efficacy of CAR-EVs in cancer patients. This review also summarizes preliminary findings and challenges, proposing strategies to improve EV targeting and cargo delivery. Additionally, this review highlights unexplored aspects of EV biology in the context of CAR T-cell therapies. In conclusion, CAR-EVs offer a viable option for cancer therapy, with potential advantages over conventional CAR T-cell therapies. However, future research is needed to optimize manufacturing, distribution, and clinical application for achieve maximum therapeutic efficacy and favorable patient outcomes.

Background: Breast cancer is the most commonly diagnosed cancer for women. Cisplatin is one the most potent chemotherapeutic drugs we know in breast cancer, but its systemic toxicity limits its clinical application. Hydrogels are a local drug delivery system that limits the systemic toxicity of drugs and improves their efficacy.

Objectives: This systematic review and meta-analysis evaluated the preclinical efficacy of cisplatin-loaded hydrogels for breast cancer treatment.

Methods: We had a systematic search on different databases, including PubMed, Scopus, MEDLINE, Embase, Google Scholar, and the Web of Science, to find relative papers.

Results: There was no statistically significant difference in cell viability between the cisplatin-loaded hydrogel and free cisplatin groups. However, the IC50 values were significantly higher in the treatment group, which means the cytotoxicity was reduced in the cisplatin-loaded hydrogel; then, we subgrouped them based on cell line and treatment duration; no significant difference was observed between the subgroups.

Conclusions: This meta-analysis evaluated cisplatin-loaded hydrogels versus free cisplatin in breast cancer treatment. Contrary to expectations, no significant difference in cell viability was found, indicating hydrogels did not enhance therapeutic efficacy. However, a significantly higher IC50 with hydrogels suggests reduced instantaneous drug concentration due to sustained release.

Prospero: CRD42025641451.

Objectives: The study aimed to investigate superparamagnetic iron oxide nanoparticles (SPIONs) as carriers for brain-targeted delivery of the anticancer drug docetaxel (DTX). The use of an externally positioned magnet was explored to achieve targeted delivery to specific regions of interest, enhancing SPIONs' accumulation and retention within the brain.

Methods: SPIONs were synthesized using the co-precipitation method. Docetaxel-loaded SPION-PLGA nanoparticles (G-SPIO/DTX-PLGA-NPs) were subsequently prepared using a solvent evaporation process and further coated with glutathione (GSH) to enhance brain targeting in male Wistar rats.

Results: The G-SPIO/DTX-PLGA-NPs demonstrated a particle size of 190 ± 5.11 nm and a zeta potential of -27.6 ± 0.36 mV. Drug release studies indicated an initial burst release of 15.03 ± 2.33% at 1 h and a sustained release of 78.78 ± 3.50% at 96 h. Cytotoxicity studies revealed significantly higher cell death (84.71%) with the G-SPIO/DTX-PLGA-NPs compared to DTX alone (72.29%), with a 3.39-fold (p < 0.001) reduction in IC₅₀ values. In vivo biodistribution analysis showed that magnetically guided G-SPIO/DTX-PLGA-NPs achieved brain tissue concentrations 21.94 times (p < 0.05) higher than free DTX and 1.46 times higher than non-magnetically guided G-SPIO/DTX-PLGA-NPs.

Conclusion: The study established G-SPIO/DTX-PLGA-NPs as effective SPION-based carriers for targeted docetaxel delivery to the brain.

Background: Paroxetine HCl (PRX-HCl), an antidepressant, has poor water solubility and low oral bioavailability with 50% being metabolized in the liver. The oral formulations have multiple side effects. The present work aimed to develop dissolving microneedle patches (MNPs) of PRX-HCl to resolve low bioavailability and side effect issues while achieving enhanced transdermal delivery.

Materials and methods: Three silicone templates of varying dimensions were used to fabricate 27 blank and nine PRX-HCl MNPs with PVP and PVA through mold casting method. MNPs were evaluated for physicochemical properties, in-vitro release, and ex-vivo permeation. The optimized MNP was further analyzed for FTIR, DSC, skin penetration, in-silico PBPK modeling, and stability.

Results: MNPs from the optimized formulation successfully created microchannels in rat skin, demonstrated higher permeation than control MNPs with a flux of 146.18 ± 13.42 µg/cm²/h, presented a decrease in lag phase and an increase in drug plasma C_max and AUC compared to PAXIL CR 12.5 mg oral, and showed higher stability in the room and refrigerator conditions.

Conclusion: The prepared MNPs were stable and can deliver PRX-HCl sufficiently across skin barrier with enhanced bioavailability compared to oral administration at similar doses and thus be a better alternative to already available delivery systems for PRX-HCl.