Tolterodine Tartrate Loaded Cationic Elastic Liposomes for Transdermal Delivery: In Vitro, Ex Vivo, and In Vivo Evaluations.

IF 3.5 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Pharmaceutical Research Pub Date : 2024-08-01 Epub Date: 2024-07-24 DOI:10.1007/s11095-024-03741-y

Mohhammad Ramzan, Afzal Hussain, Tasneem Khan, Mohd Usman Mohd Siddique, Musarrat Husain Warsi

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引用次数: 0

Abstract

Objective: Tolterodine tartrate (TOTA) is a first-line therapy to treat overactive urinary bladder (OAB). Oral delivery causes high hepatic clearance, xerostomia, headache, constipation, and blurred vision. We addressed Hansen solubility parameter (HSP) and Design Expert oriented optimized cationic elastic liposomes for transdermal application.

Methods: The experimental solubility was conducted in HSPiP predicted excipients to tailor formulations using surfactants, stearylamine, ethanol, and phosphatidylcholine (PC). These were evaluated for formulation characteristics. The optimized OTEL1 and OTEL1-G (gel) were compared against the drug solution (DS) and liposomes. In vitro and ex vivo studies were accomplished to investigate the insights into the mechanistic understanding of TOTA release and permeation ability. Finally, confocal laser scanning microscopy (CLSM) supported ex vivo results.

Results: HSP values of TOTA were closely related to tween-80, stearylamine, and human's skin. The size (153 nm), %EE (87.6%), and PDI (0.25) values of OTEL1 were in good agreement to the predicted values (161 nm, 80.4%, and 0.31) with high desirability (0.963). Spherical and smooth OTEL1 (including OTEL1-G and liposomes) vesicles followed non-Fickian drug release as compared to DS (Fickian) as evidence with n > 0.5 (Korsmeyer and Peppas coefficient). OTEL1 (containing lipid and surfactant as 90 mg and 13.8 mg, respectively) exhibited 2.6 and 1.8-folds higher permeation flux than DS and liposomes, respectively. Biocompatible cationic OTEL1 was safe and non-hemolytic.

Conclusions: OTEL1 was promised as a lead vesicular approach and an alternative to conventional oral therapy to treat OAB in children and advanced age patients.

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用于透皮给药的酒石酸托特罗定负载阳离子弹性脂质体：体外、体内和体内评估。

目的：酒石酸托特罗定（TOTA）是治疗膀胱过度活动症（OAB）的一线疗法。口服给药会导致较高的肝清除率、口干、头痛、便秘和视力模糊。我们研究了汉森溶解度参数（HSP），并以设计专家为导向，优化了阳离子弹性脂质体的透皮应用：方法：利用汉森溶解度参数（HSPiP）预测辅料的实验溶解度，使用表面活性剂、硬脂胺、乙醇和磷脂酰胆碱（PC）定制配方。对这些辅料的配方特性进行了评估。将优化后的 OTEL1 和 OTEL1-G（凝胶）与药物溶液（DS）和脂质体进行了比较。为了深入了解 TOTA 释放和渗透能力的机理，还进行了体外和体内研究。最后，共焦激光扫描显微镜（CLSM）为体内外研究结果提供了支持：结果：TOTA 的 HSP 值与吐温-80、硬脂胺和人体皮肤密切相关。OTEL1 的尺寸（153 nm）、%EE（87.6%）和 PDI（0.25）值与预测值（161 nm、80.4% 和 0.31）非常吻合，可取性高（0.963）。球形和光滑的 OTEL1（包括 OTEL1-G 和脂质体）囊泡与 DS（费克）囊泡相比遵循非费克药物释放，n > 0.5（Korsmeyer 和 Peppas 系数）即为证据。OTEL1（分别含有 90 毫克脂质和 13.8 毫克表面活性剂）的渗透通量分别比 DS 和脂质体高 2.6 倍和 1.8 倍。生物相容性阳离子 OTEL1 安全且不溶血：OTEL1有望成为治疗儿童和高龄患者OAB的主要囊泡方法和传统口服疗法的替代品。

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来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.