载硫酸软骨素包覆石榴脂质载体的纳米杂交热敏水凝胶经空心微针皮内递送用于有效治疗类风湿性关节炎

IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Mariam Zewail , Haidy Abbas , Nesrine El Sayed , Nihal M. El Newehy , Heba Abd-El-Azim
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引用次数: 0

摘要

类风湿关节炎(RA)是一种常见的炎症性关节炎,严重影响身体功能,导致日常活动受限。本研究旨在利用石榴皮提取物(POM)开发一种有效的纳米给药系统来治疗RA。POM包被在纳米结构脂质载体(NLCs)中,包被硫酸软骨素(CHS),积极靶向风湿性关节中过表达的CD44受体。将优化后的NLCs装入Pluronic F127水凝胶中,制备热敏纳米杂化水凝胶,通过AdminPen™MNs空心微针(Ho-MNs)皮内给药。UPLC-ESI-MS/MS分析鉴定了76种化合物,主要是多酚,具有抗炎和抗氧化特性。采用熔融乳化法制备的nlc粒径范围为64.7±0.34 ~ 341±2.5 nm, zeta电位范围为- 17±1.34 mV ~ - 30±0.98 mV,包封效率为96.34±0.34 ~ 98.89±0.12%。纳米杂化水凝胶将POM的释放期从6天延长至13天,并减少了爆裂效应。体外研究证实AdminPen™MNs可有效渗透皮肤。对AIA大鼠的体内研究表明,POM纳米杂交水凝胶可显著缓解关节肿胀,降低TNF-α、IL-1β、MDA和MMP-3水平,同时增加NRF2水平。组织病理学检查显示,纳米杂化水凝胶处理组关节和软骨结构正常。该新系统为RA治疗提供了一种微创、缓释的方法,提高了POM的生物利用度和治疗效果,从而为传统治疗提供了一种有希望的替代方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Intradermal delivery of nanohybrid thermosensitive hydrogels loaded with chondroitin sulphate coated pomegranate lipid carriers via hollow microneedles for effective rheumatoid arthritis management

Intradermal delivery of nanohybrid thermosensitive hydrogels loaded with chondroitin sulphate coated pomegranate lipid carriers via hollow microneedles for effective rheumatoid arthritis management
Rheumatoid Arthritis (RA) is a common inflammatory arthritis type that significantly affects physical functions, leading to restrictions in daily activities. The current study aims to develop an effective nano-based drug delivery system for RA management using pomegranate peel extract (POM). POM was encapsulated in nanostructured lipid carriers (NLCs), coated with chondroitin sulphate (CHS) to actively target CD44 receptors that are over expressed in rheumatic joints. The optimized NLCs were loaded into Pluronic F127 hydrogels to prepare thermosensitive nanohybrid hydrogels for intradermal administration via AdminPen™ MNs hollow microneedles (Ho-MNs). The UPLC-ESI-MS/MS analysis of POM identified 76 compounds, predominantly polyphenols, known for anti-inflammatory and antioxidant properties. NLCs were prepared using the melt emulsification method, showing particle sizes ranging from 64.7 ± 0.34 to 341 ± 2.5 nm, zeta potentials between −17 ± 1.34 mV and −30 ± 0.98 mV, and high entrapment efficiencies (96.34 ± 0.34–98.89 ± 0.12 %). Nanohybrid hydrogels extended the release period of POM from 6 days to 13 days and reduced burst effects. Ex vivo studies confirmed effective skin penetration by AdminPen™ MNs. In vivo studies in rats with AIA demonstrated that POM nanohybrid hydrogels significantly relieved joint swelling and reduced TNF-α, IL-1β, MDA, and MMP-3 levels, while increasing NRF2 level. Histopathological examination revealed that the nanohybrid hydrogel-treated group had normal joint and cartilage structure. This novel system offers a minimally invasive, sustained-release approach for RA treatment, enhancing bioavailability and the therapeutic efficacy of POM, thus providing a promising alternative to conventional therapies.
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来源期刊
CiteScore
8.00
自引率
8.00%
发文量
879
审稿时长
94 days
期刊介绍: The Journal of Drug Delivery Science and Technology is an international journal devoted to drug delivery and pharmaceutical technology. The journal covers all innovative aspects of all pharmaceutical dosage forms and the most advanced research on controlled release, bioavailability and drug absorption, nanomedicines, gene delivery, tissue engineering, etc. Hot topics, related to manufacturing processes and quality control, are also welcomed.
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