High drug loading hydrophobic cross-linked dextran microspheres as novel drug delivery systems for the treatment of osteoarthritis

IF 10.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY Asian Journal of Pharmaceutical Sciences Pub Date : 2023-07-01 DOI:10.1016/j.ajps.2023.100830
Zhimin Li , Xianjing Feng , Shixing Luo , Yanfeng Ding , Zhi Zhang , Yifeng Shang , Doudou Lei , Jinhong Cai , Jinmin Zhao , Li Zheng , Ming Gao
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Abstract

Drug delivery via intra-articular (IA) injection has proved to be effective in osteoarthritis (OA) therapy, limited by the drug efficiency and short retention time of the drug delivery systems (DDSs). Herein, a series of modified cross-linked dextran (Sephadex, S0) was fabricated by respectively grafting with linear alkyl chains, branched alkyl chains or aromatic chain, and acted as DDSs after ibuprofen (Ibu) loading for OA therapy. This DDSs expressed sustained drug release, excellent anti-inflammatory and chondroprotective effects both in IL-1β induced chondrocytes and OA joints. Specifically, the introduction of a longer hydrophobic chain, particularly an aromatic chain, distinctly improved the hydrophobicity of S0, increased Ibu loading efficiency, and further led to significantly improving OA therapeutic effects. Therefore, hydrophobic microspheres with greatly improved drug loading ratio and prolonged degradation rates show great potential to act as DDSs for OA therapy.

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高载药疏水性交联葡聚糖微球作为治疗骨关节炎的新型药物递送系统
通过关节内(IA)注射给药已被证明在骨关节炎(OA)治疗中是有效的,但受给药系统(DDS)的药物效率和短停留时间的限制。本文通过分别与直链烷基链、支链烷基链或芳香链接枝制备了一系列改性交联葡聚糖(Sephadex,S0),并在布洛芬(Ibu)负载后作为DDSs用于OA治疗。该DDS在IL-1β诱导的软骨细胞和OA关节中均表现出持续的药物释放、优异的抗炎和软骨保护作用。具体而言,引入较长的疏水链,特别是芳族链,显著提高了S0的疏水性,提高了Ibu负载效率,并进一步显著提高了OA的治疗效果。因此,疏水性微球具有显著提高的载药率和延长的降解率,显示出作为DDSs治疗OA的巨大潜力。
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来源期刊
Asian Journal of Pharmaceutical Sciences
Asian Journal of Pharmaceutical Sciences Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
18.30
自引率
2.90%
发文量
11
审稿时长
14 days
期刊介绍: The Asian Journal of Pharmaceutical Sciences (AJPS) serves as the official journal of the Asian Federation for Pharmaceutical Sciences (AFPS). Recognized by the Science Citation Index Expanded (SCIE), AJPS offers a platform for the reporting of advancements, production methodologies, technologies, initiatives, and the practical application of scientific knowledge in the field of pharmaceutics. The journal covers a wide range of topics including but not limited to controlled drug release systems, drug targeting, physical pharmacy, pharmacodynamics, pharmacokinetics, pharmacogenomics, biopharmaceutics, drug and prodrug design, pharmaceutical analysis, drug stability, quality control, pharmaceutical engineering, and material sciences.
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