用于增强甲氨蝶呤透皮给药的 Transethosomes 的配制、表征和优化

IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Priyanka J. Veer, Vinayak S. Mastiholimath
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引用次数: 0

摘要

目的甲氨蝶呤(MTX)是一种抗肿瘤药物,用于治疗类风湿性关节炎(RA)。鉴于它是一种渗透性和溶解性都很低的 IV 类药物,本研究旨在通过将 MTX 装入透硫体(TEs)并制成透硫体贴片来改善其皮肤渗透性,从而实现剂量定量以减轻毒性。方法为了实现这一目标,我们采用薄膜水合技术开发了 MTX 转乙体(TEs),并以大豆磷脂酰胆碱 50、吐温 80 和乙醇为自变量,使用方框-贝肯设计(BBD)和理想函数对其进行了优化。此外,还使用了 zeta 电位(ZP)分析和高分辨率透射电子显微镜(HR-TEM)来确认 TEs 的稳定性和表面形态。此外,还采用溶剂浇注法,以羟丙基甲基纤维素(HPMC)为聚合物、二甲基亚砜(DMSO)为渗透促进剂、聚乙二醇(PEG 400)为增塑剂,设计并评估了优化 TE(OPTZ TEs)批次的透皮贴片。此外,大鼠皮肤的体外渗透和沉积证明,TE 贴片在皮肤层内具有更好的药物渗透和保留效果。结果最高理想批次的囊泡大小为 92.19 ± 3.826 nm,PDI 为 0.35 ± 0.062,EE 为 74.05 ± 5.157%,Q8h 为 62.75 ± 4.448%,均在预测结果范围内。此外,ZP 大于 - 30 mV,HR-TEM 结果证明 TE 囊泡呈球形。重量变化、耐折度和厚度等评价参数的结果分别为 0.07 ± 0.01 克、82.3 ± 1.52 折和 0.93 ± 0.01,均在限值范围内。经药物含量分析证实,TE 贴片含有 90% 以上的药物,可在体内渗透近 24 小时,与 MTX 溶液相比,具有持续释放作用,渗透通量为 19 ± 1.08,增强比为 3.68。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Formulation, Characterization, and Optimization of Transethosomes for Enhanced Transdermal Delivery of Methotrexate

Formulation, Characterization, and Optimization of Transethosomes for Enhanced Transdermal Delivery of Methotrexate

Purpose

Methotrexate (MTX) is an antineoplastic drug used in the treatment of rheumatoid arthritis (RA). Given that it is a class IV drug with low permeability and solubility, this study aims to improve MTX skin permeation by loading it in transethosomes (TEs) and casting a transethosomal patch that allows for dose quantification to mitigate toxicity.

Methods

To accomplish this goal, MTX transethosomes (TEs) were developed using the thin film hydration technique and optimized using the Box-Behnken design (BBD) with soya phosphatidylcholine 50, Tween 80, and ethanol as independent variables using the desirability function. Furthermore, zeta potential (ZP) analysis and high-resolution transmission electron microscopy (HR-TEM) were used to confirm the stability and surface morphology of TEs. A transdermal patch was also designed and evaluated from the optimized TE (OPTZ TEs) batch using a solvent casting method with hydroxypropyl methylcellulose (HPMC) as the polymer, dimethyl sulfoxide (DMSO) as a permeation enhancer, and polyethylene glycol (PEG 400) as the plasticizer. Furthermore, ex vivo skin permeation and deposition through rat skin proved that the TE patch had better drug permeation and retention within the skin layers.

Results

The highest desirability batch had 92.19 ± 3.826 nm vesicle size, 0.35 ± 0.062 PDI, 74.05 ± 5.157% EE and 62.75 ± 4.448% Q8h which were within the predicted results. Furthermore, ZP was found to be more than − 30 mV, and HR-TEM results proved that the TE vesicles were spherical. The results of the evaluation parameters such as weight variation, folding endurance, and thickness were 0.07 ± 0.01 g, 82.3 ± 1.52 folds, and 0.93 ± 0.01, respectively, and were well within the limits. The TE patch incorporated more than 90% of the drug confirmed by the drug content analysis which allowed ex vivo permeation for almost 24 h providing a sustained release action with a permeation flux of 19 ± 1.08 and an enhancement ratio of 3.68 when compared to the MTX solution.

Conclusion

This study suggests that MTX-loaded transethosomal patch not only enhanced the skin permeation but also provided a 24-h release profile and reduced its toxicity.

Graphical Abstract

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来源期刊
Journal of Pharmaceutical Innovation
Journal of Pharmaceutical Innovation PHARMACOLOGY & PHARMACY-
CiteScore
3.70
自引率
3.80%
发文量
90
审稿时长
>12 weeks
期刊介绍: The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories: Materials science, Product design, Process design, optimization, automation and control, Facilities; Information management, Regulatory policy and strategy, Supply chain developments , Education and professional development, Journal of Pharmaceutical Innovation publishes four issues a year.
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