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高压匀质-溶剂蒸发技术包载倍他米松戊酸酯纳米乳的研究:优化制剂和工艺参数以实现高效的皮肤靶向给药。

Nanoencapsulation of betamethasone valerate using high pressure homogenization-solvent evaporation technique: optimization of formulation and process parameters for efficient dermal targeting.

机构信息

a Department of Pharmaceutical Technology, School of Pharmacy , International Medical University , Kuala Lumpur , Malaysia.

b Johar Institute of Professional Studies Lahore , Punjab , Pakistan.

出版信息

Drug Dev Ind Pharm. 2019 Feb;45(2):323-332. doi: 10.1080/03639045.2018.1542704. Epub 2018 Nov 20.

DOI:10.1080/03639045.2018.1542704
PMID:30404554
Abstract

Betamethsone valerate (BMV), a medium potency topical corticosteroid, is one of the most commonly employed pharmacological agents for the management of atopic dermatitis in both adults and children. Despite having remarkable pharmacological efficacy, these agents have limited clinical implication due to poor penetration across the startum cornum (SC). To mitigate issues related to targeted delivery, stability, and solubility as well as to potentiate therapeutic and clinical implication, the nanodelivery systems have gained remarkable recognition. Therefore, this study was aimed to encapsulate BMV into the chitosan nanoparticles (CS-NPs) for optimum dermal targeting and improved penetration across the SC. The prepared NPs were characterized for particle size, zeta potential, polydispersity index, entrapment efficiency, loading capacity, crystallinity, thermal behavior, morphology, in vitro release kinetics, drug permeation across the SC, and percentage of drug retained into various skin layers. Results showed that optimized BMV-CS-NPs exhibited optimum physicochemical characteristics including small particle size (< 250 ± 28 nm), higher zeta potential (+58 ± 8 mV), and high entrapment efficiency (86 ± 5.6%) and loading capacity (34 ± 7.2%). The in vitro release study revealed that BMV-CS-NPs displayed Fickian-diffusion type mechanism of release in simulated skin surface (pH 5.5). Drug permeation efficiency and the amount of BMV retained into the epidermis and the dermis were comparatively higher in case of BMV-CS-NPs compared to BMV solution. Conclusively, we anticipated that BMV-CS-NPs could be a promising nanodelivery system for efficient dermal targeting of BMV and improved anti-AD efficacy.

摘要

倍他米松戊酸酯(BMV)是一种中效外用皮质类固醇,是治疗成人和儿童特应性皮炎最常用的药物之一。尽管具有显著的药理学功效,但由于难以穿透角质层(SC),这些药物的临床应用有限。为了解决靶向递送、稳定性和溶解度方面的问题,并增强治疗和临床效果,纳米递药系统得到了广泛的认可。因此,本研究旨在将 BMV 包封到壳聚糖纳米粒(CS-NPs)中,以实现最佳的皮肤靶向和改善穿透角质层的能力。所制备的 NPs 进行了粒径、zeta 电位、多分散指数、包封效率、载药量、结晶度、热行为、形态学、体外释放动力学、药物透过角质层、以及药物在各种皮肤层中的滞留率等方面的表征。结果表明,优化后的 BMV-CS-NPs 表现出最佳的物理化学特性,包括较小的粒径(<250±28nm)、较高的 zeta 电位(+58±8mV)以及高的包封效率(86±5.6%)和载药量(34±7.2%)。体外释放研究表明,BMV-CS-NPs 在模拟皮肤表面(pH5.5)中呈现出菲克扩散型释放机制。与 BMV 溶液相比,BMV-CS-NPs 具有更高的药物渗透效率和进入表皮和真皮的 BMV 量。综上所述,我们预计 BMV-CS-NPs 可能是一种有前途的纳米递药系统,可实现 BMV 的高效皮肤靶向和提高抗 AD 效果。

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