用于阿托伐他汀钙透皮给药的超柔性脂质体:流变学和体内外评估

IF 1.8 3区 农林科学 Q3 FOOD SCIENCE & TECHNOLOGY
Mohamed A. Akl, Sherif Ryad, Mohamed F. Ibrahime, Alaa A. Kassem
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引用次数: 0

摘要

我们的研究旨在探索将阿托伐他汀钙 (ATC) 加入超柔性纳米囊泡 (UFNV) 的可能性,以避免肝脏的首次代谢,提高其作为口服治疗潜在替代品的有效性。我们采用旋转蒸发-声化法开发了 ATC 纳米囊泡,并对其囊泡直径、ZP(Zeta 电位)、包埋效率(EE)以及体外释放研究进行了体外评估。所选的 ATC-UFNVs 配方被整合到不同的凝胶基质中,并对其含量均匀性、pH 值、铺展能力、粘度和流变行为进行了评估。使用体外渗透和激光共聚焦显微镜图像(CLSM)对制备的纳米颗粒的皮肤渗透性进行了评估。ATC 负载 UFNV 的体外评估显示,纳米颗粒的平均直径介于 60.84 ± 0.53 nm 和 91.68 ± 2.11 nm 之间,Zeta 电位值介于 -15.8 ± 0.31 至 -25.1 ± 0.81 mV 之间,EE%介于 84.33 ± 1.94 和 86.53 ± 2.02% 之间,制剂的 ATC 释放率为 75.25-90.89%。所有释放模式均按照樋口扩散法进行了动力学分析。含有 ATC-UF 的 Carbapol 934 凝胶基质呈现出非牛顿假塑性流动,触变性等于 2.013 cm2。体内外数据显示,与游离 AC 相比,ATC-UFNV 的渗透性更好。CLSM 显示,与不含罗丹明 B 的溶液(50 微米)相比,UF-纳米囊在皮肤中的渗透深度达 90 微米,表现出更强更深的荧光信号。我们的研究最终证明了 ATC-UFNVs 凝胶配方的透皮能力:本研究中成功开发的阿托伐他汀钙负载型超柔性纳米粒子(ATC-UFNVs)为研究人员和医疗保健专业人员提供了广阔的应用前景。这些纳米颗粒能够绕过肝脏的首过代谢,增强药物在皮肤上的输送,这为口服药物提供了一种潜在的替代方案,而口服药物可能会产生胃肠道副作用,吸收情况也不尽相同。这项研究成果可用于开发新型透皮给药系统,治疗各种心血管疾病。ATC-UFNV 可被纳入治疗高胆固醇血症的外用制剂中,从而减少对全身用药的需求。此外,还可以利用本研究获得的启示,探索使用纳米颗粒给药其他亲脂性药物的可行性,从而扩大其潜在的治疗应用范围。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Ultraflexible liposomes for transdermal delivery of atorvastatin calcium: Rheological and ex vivo evaluation

Ultraflexible liposomes for transdermal delivery of atorvastatin calcium: Rheological and ex vivo evaluation

Our research aims to explore the possibility of incorporating atorvastatin calcium (ATC) in ultraflexible nanovesicles (UFNVs) to avoid the hepatic first metabolism and enhance its effectiveness as a potential alternative to oral treatment. ATC nanovesicles were developed utilizing the rotary evaporation-sonication method and assessed in vitro concerning their vesicle diameter, zeta potential (ZP), entrapment efficiency (EE), as well as in vitro release studies. The chosen formulation of ATC-UFNVs was integrated into a different gel base that was evaluated for content uniformity, pH, spreading ability, viscosity, and rheological behavior. The skin permeation of the prepared nanovesicles was assessed using an ex vivo permeation and confocal laser microscopy images (CLSM). In vitro evaluation of the ATC-loaded UFNVs showed that the mean diameter of the nanovesicles ranging between 60.84 ± 0.53 nm and 91.68 ± 2.11 nm, the Zeta potential values ranged from of –15.8 ± 0.31 to –25.1 ± 0.81 mV, the EE% were between 84.33 ± 1.94 and 86.53 ± 2.02%, and the ATC release from the formulations was 75.25–90.89%. All release patterns were analyzed kinetically following Higuchi's diffusion approach. Carbapol 934 gel bases containing ATC-UF exhibited non-Newtonian pseudo-plastic flow with thixotropy equal to 2.013 cm2. Ex vivo data showed that ATC-UFNVs had better penetration compared to free AC. CLSM revealed that the UF-nanovesicle exhibited stronger and deeper fluorescence signals up to 90 µm depth of permeation in skin versus the rhodamine B-free solution (50 µm). The transdermal ability of the ATC-UFNVs gel formulation has been conclusively demonstrated by our research.

Practical Applications: The successful development of atorvastatin calcium-loaded ultraflexible nanovesicles (ATC-UFNVs) in this study offers promising applications for researchers and healthcare professionals. The ability of these nanovesicles to bypass hepatic first-pass metabolism and enhance drug delivery to the skin presents a potential alternative to oral administration, which can be associated with gastrointestinal side effects and variable absorption. The findings of this research can be applied in the development of novel transdermal drug delivery systems for the treatment of various cardiovascular conditions. ATC-UFNVs may be incorporated into topical formulations for the management of hypercholesterolemia, reducing the need for systemic medication. Additionally, the insights gained from this study could be utilized to explore the feasibility of using nanovesicles for the delivery of other lipophilic drugs, expanding their potential therapeutic applications.

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来源期刊
CiteScore
5.50
自引率
0.00%
发文量
101
审稿时长
6-16 weeks
期刊介绍: The European Journal of Lipid Science and Technology is a peer-reviewed journal publishing original research articles, reviews, and other contributions on lipid related topics in food science and technology, biomedical science including clinical and pre-clinical research, nutrition, animal science, plant and microbial lipids, (bio)chemistry, oleochemistry, biotechnology, processing, physical chemistry, and analytics including lipidomics. A major focus of the journal is the synthesis of health related topics with applied aspects. Following is a selection of subject areas which are of special interest to EJLST: Animal and plant products for healthier foods including strategic feeding and transgenic crops Authentication and analysis of foods for ensuring food quality and safety Bioavailability of PUFA and other nutrients Dietary lipids and minor compounds, their specific roles in food products and in nutrition Food technology and processing for safer and healthier products Functional foods and nutraceuticals Lipidomics Lipid structuring and formulations Oleochemistry, lipid-derived polymers and biomaterials Processes using lipid-modifying enzymes The scope is not restricted to these areas. Submissions on topics at the interface of basic research and applications are strongly encouraged. The journal is the official organ the European Federation for the Science and Technology of Lipids (Euro Fed Lipid).
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