Therapeutic delivery最新文献

Aim: The study explores glycerosomes as effective vesicular systems for transdermal delivery of atorvastatin (ATO) to overcome drawbacks related to its oral administration.Methodology: The objectives of this study were to formulate, by thin-film hydration method, optimize using definitive screening design and evaluate ATO-loaded glycerosomes (ATOG) which were then incorporated into patch followed by the evaluation of glycerosomes containing different concentration of glycerol.Results & discussion: Vesicle size, Polydispersity index (PDI), zeta potential, entrapment efficiency and loading capacity of spherical ATOG (0-30%w/w) showed 137.3-192d.nm, 0.292-0.403, -3.81 to-6.76mV, 80.03-92.77% and 5.80-6.40%, respectively. In-vitro release study showed sustained release, increased skin permeability and better cell viability than pure drug. ATOG patches showed greater skin permeability than pure drug and ATO-liposomal patches.Conclusion: The study concludes that ATOGs are promising for effective transdermal delivery.

Aim: Dasatinib (DST) is an oral tyrosine kinase inhibitor with poor aqueous solubility. To outwit this issue, a solid self-nano emulsifying drug delivery system (S-SNEDDS) of DST was formulated.Methods: I-optimal mixture design was used for optimization of DST-loaded SNEDDS using Linalool, Cremophor RH40 and Transcutol P. S-SNEDDS underwent physicochemical characterization, in-vitro release and ex-vivo permeation, cell-based assays and pharmacokinetic study.Results: DST-S-SNEDDS showed globule size and PDI of 141.53 ± 5.371 nm and 0.282 ± 0.020, respectively. DST-S-SNEDDS revealed significantly lower IC₅₀ (1.825 μg/mL) than free DST (7.298 μg/mL) in MDA-MB-231. In-vivo pharmacokinetic study revealed 1.94-fold increment in AUC_0-t for the DST-S-SNEDDS group than free DST.Conclusion: S-SNEDDS could be promising approach for improving bioavailability and efficacy of DST.

Aim: The current study aims to develop and optimize microemulsions (ME) through Quality-by-Design (QbD) approach to improve the aqueous solubility and dissolution of poorly water-soluble drug disulfiram (DSF) for repurposing in melanoma and breast cancer therapy.Materials & methods: The ME was formulated using Cinnamon oil & Tween^® 80, statistically optimized using a D-optimal mixture design-based QbD approach to develop the best ME with low vesicular size (Z_avg) and polydispersity index (PDI).Results: The DSF-loaded optimized stable ME showed enhanced dissolution, in-vitro cytotoxicity and improved cellular uptake in B16F10 and MCF-7 cell lines compared with their unformulated free DSF.Conclusion: Our investigations suggested the potential of the statistically designed DSF-loaded optimized ME for repurposing melanoma and breast cancer therapy.

Aim: This study aimed to formulate erlotinib hydrochloride (ERT-HCL)-loaded chitosan (CS) and poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) using Quality-by-Design (QbD) to optimize critical quality attributes (CQAs). Materials & methods: Quality target product profile (QTPP) and CQAs were initially established. Based on L8-Taguchi screening and risk assessments, central composite design (CCD) design was used to optimize NPs. Results: ERT-HCL-loaded CS-PLGA NPs had a mean particle diameter, zeta potential and entrapment efficiency of 226.50 ± 1.62 d.nm, 27.66 ± 0.64 mV and 78.93 ± 1.94 %w/w, respectively. The NPs exhibited homogenous spherical morphology and sustained release for 72 h. Conclusion: Using systematic QbD approach, ERT-HCL was encapsulated in CS-PLGA NPs, optimizing CQAs. These findings propel future research for improved NSCLC treatment.

Aim: To achieve colon-targeted release of mefenamic acid from its ester-linked amylose prodrugs.Materials & methods: The prodrug was characterized by 1H NMR and IR spectroscopy. Drug activation and release profile was studied in enzyme enriched simulated physiological media via UV-vis spectroscopy and was validated with HPLC analysis. ELISA assay was employed for evaluating the % inhibition of COX-1 and COX-2 inhibition at different concentrations of the prodrug preincubated with ester and/ or amylose hydrolyzing enzymes. SEM studies further validated the performance of the prodrug under simulated physiological conditions.Results: Pancreatin was essential for the prodrug activation in SIM to make the ester bonds in prodrug vulnerable to hydrolysis by esterase. This evidence was confirmed by drug release studies, HPLC analysis, ELISA assay and SEM investigation where the ester conjugated prodrug showed marked stability in physiological media only to get activated in the presence of amylose degrading enzyme.Conclusion: Ester linked amylose-mefenamic acid conjugate showed both enzyme responsive activation and release in SIM.

Aim: Benznidazole (BNZ), a class-II drug, is the primary treatment for Chagas disease, but its low aqueous solubility presents challenges in formulation and efficacy. Nanosuspensions (NS) could potentially address these issues.Methods: BNZ-NS were prepared using a simple, organic solvents-free nano-milling approach. Physicochemical characterizations were conducted on both NS and lyophilized solid-state BNZ-nanocrystals (NC).Results: BNZ-NS exhibited particle size <500 nm, an acceptable polydispersity index (0.23), high Z-potential, and physical stability for at least 90 days. BNZ-NC showed tenfold higher solubility than pure BNZ. Dissolution assays revealed rapid BNZ-NS dissolution. BNZ-NC demonstrated biocompatibility on an eukaryotic cell and enhanced BNZ efficacy against trypomastigotes of Trypanosoma cruzi.Conclusion: BNZ-NS offers a promising alternative, overcoming limitations associated with BNZ for optimized pharmacotherapy.

Aim: Design of moxifloxacin and ornidazole co-loaded polycaprolactone and gelatin nanofiber dressing for diabetic wounds. Materials & methods: The composite nanofibers were prepared using electrospinning technique and characterized for in vitro drug release, antibacterial activity, laser doppler and in vivo wound healing. Results: The optimized nanofiber demonstrated an interconnected bead free nanofiber with average diameter <200 nm. The in vitro drug release & antimicrobial studies revealed that optimized nanofiber provided drug release for >120 h, thereby inhibiting growth of Escherichia coli and Stapyhlococcus aureus. An in vivo wound closure study on diabetic rats found that optimized nanofiber group had a significantly higher wound closure rate than marketed formulation. Conclusion: The nanofiber provided prolonged drug release and accelerated wound healing, making it a promising candidate for diabetic wound care.