Dravid Ameya A, M Dhanabalan Kaamini, Agarwal Smriti, Agarwal Rachit
BioSystems Science and Engineering Indian Institute of Science Bangalore Karnataka India.
Bioeng Transl Med. 2022 Mar 7;7(2):e10281. doi: 10.1002/btm2.10281. eCollection 2022 May.
Current treatments for osteoarthritis (OA) offer symptomatic relief but do not prevent or halt the disease progression. Chronic low-grade inflammation is considered a significant driver of OA. Specialized proresolution mediators are powerful agents of resolution but have a short in vivo half-life. In this study, we have engineered a Resolvin D1 (RvD1)-loaded nanoliposomal formulation (Lipo-RvD1) that targets and resolves the OA-associated inflammation. This formulation creates a depot of the RvD1 molecules that allows the controlled release of the molecule for up to 11 days in vitro. In surgically induced mice model of OA, only controlled-release formulation of Lipo-RvD1 was able to treat the progressing cartilage damage when administered a month after the surgery, while the free drug was unable to prevent cartilage damage. We found that Lipo-RvD1 functions by damping the proinflammatory activity of synovial macrophages and recruiting a higher number of M2 macrophages at the site of inflammation. Our Lipo-RvD1 formulation was able to target and suppress the formation of the osteophytes and showed analgesic effect, thus emphasizing its ability to treat clinical symptoms of OA. Such controlled-release formulation of RvD1 could represent a patient-compliant treatment for OA.
骨关节炎（OA）的现有治疗方法可缓解症状，但无法预防或阻止疾病进展。慢性低度炎症被认为是OA的一个重要驱动因素。专门的促消退介质是强大的消退剂，但在体内半衰期较短。在本研究中，我们设计了一种负载消退素D1（RvD1）的纳米脂质体制剂（Lipo-RvD1），其靶向并消退与OA相关的炎症。该制剂形成了RvD1分子储存库，可在体外实现该分子长达11天的控释。在手术诱导的OA小鼠模型中，仅Lipo-RvD1的控释制剂在手术后一个月给药时能够治疗进展性软骨损伤，而游离药物无法预防软骨损伤。我们发现Lipo-RvD1通过抑制滑膜巨噬细胞的促炎活性并在炎症部位募集更多数量的M2巨噬细胞发挥作用。我们的Lipo-RvD1制剂能够靶向并抑制骨赘形成，并显示出镇痛作用，从而突出了其治疗OA临床症状的能力。这种RvD1控释制剂可能是一种患者依从性良好的OA治疗方法。
