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透明质酸修饰的倍他米松包封聚合物纳米粒的制备、表征、体外释放动力学及皮肤靶向性研究。

Hyaluronic acid-modified betamethasone encapsulated polymeric nanoparticles: fabrication, characterisation, in vitro release kinetics, and dermal targeting.

机构信息

Department of Pharmaceutical Technology, School of Pharmacy, International Medical University-Bukit Jalil 57000, Kuala Lumpur, Malaysia.

Faculty of Pharmacy, Lincoln University College, Petaling Jaya, 47301, Kuala Lumpur, Selangor, Malaysia.

出版信息

Drug Deliv Transl Res. 2019 Apr;9(2):520-533. doi: 10.1007/s13346-018-0480-1.

Abstract

Atopic dermatitis (AD) is a chronically relapsing eczematous skin disease characterised by frequent episodes of rashes, severe flares, and inflammation. Till date, there is no absolute therapy for the treatment of AD; however, topical corticosteroids (TCs) are the majorly prescribed class of drugs for the management of AD in both adults and children. Though, topical route is most preferable; however, limited penetration of therapeutics across the startum cornum (SC) is one of the major challenges for scientists. Therefore, the present study was attempted to fabricate a moderate-potency TC, betamethasone valerate (BMV), in the form of chitosan nanoparticles (CS-NPs) for optimum dermal targeting and improved penetration across the SC. To further improve the targeting efficiency of BMV and to potentiate its therapeutic efficacy, the fabricated BMV-CS-NPs were coated with hyaluronic acid (HA). The prepared NPs were characterised for particle size, zeta potential, polydispersity index (PDI), entrapment efficiency, loading capacity, crystallinity, thermal behaviour, morphology, in vitro release kinetics, drug permeation across the SC, and percentage of drug retained into various skin layers. Results showed that optimised HA-BMV-CS-NPs exhibited optimum physicochemical characteristics including finest particle size (< 300 ± 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 HA-BMV-CS-NPs displayed Fickian diffusion-type mechanism of release in simulated skin surface (pH 5.5). Drug permeation efficiency of BMV was comparatively higher in case of BMV-CS-NPs; however, the amount of drug retained into the epidermis and the dermis was comparatively higher in case of HA-BMV-CS-NPs, compared to BMV-CS-NPs. Conclusively, we anticipate that HA-BMV-CS-NPs could be a promising nanodelivery system for efficient dermal targeting of BMV and improved anti-AD efficacy.

摘要

特应性皮炎(AD)是一种慢性复发性湿疹性皮肤病,其特征是频繁出现皮疹、严重发作和炎症。迄今为止,尚无治疗 AD 的绝对疗法;然而,局部皮质类固醇(TCs)是成人和儿童 AD 管理中主要开的药物类别。虽然,局部途径是最优选的;然而,治疗药物在角质层(SC)中的有限渗透是科学家面临的主要挑战之一。因此,本研究试图将中效 TC 倍他米松戊酸酯(BMV)制成壳聚糖纳米粒(CS-NPs),以实现最佳的皮肤靶向和改善 SC 中的渗透。为了进一步提高 BMV 的靶向效率并增强其治疗效果,将制备的 BMV-CS-NPs 用透明质酸(HA)包衣。对制备的 NPs 进行了粒径、zeta 电位、多分散指数(PDI)、包封效率、载药量、结晶度、热行为、形态、体外释放动力学、药物透过 SC 的渗透以及药物在各种皮肤层中的保留百分比进行了表征。结果表明,优化的 HA-BMV-CS-NPs 表现出最佳的物理化学特性,包括最小的粒径(<300±28nm)、更高的 zeta 电位(+58±8mV)和更高的包封效率(86±5.6%)和载药量(34±7.2%)。体外释放研究表明,HA-BMV-CS-NPs 在模拟皮肤表面(pH5.5)中表现出菲克扩散型释放机制。与 CS-NPs 相比,BMV 的药物渗透效率在 BMV-CS-NPs 中较高;然而,与 BMV-CS-NPs 相比,HA-BMV-CS-NPs 中药物保留在表皮和真皮中的量较高。总之,我们预计 HA-BMV-CS-NPs 可能是一种有前途的纳米递药系统,可实现 BMV 的高效皮肤靶向和改善抗 AD 疗效。

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