Noda Takehiro, Okuda Tomoyuki, Mizuno Ryota, Ozeki Tetsuya, Okamoto Hirokazu
Graduate School of Pharmaceutical Sciences, Nagoya City University.
Faculty of Pharmacy, Meijo University.
Biol Pharm Bull. 2018;41(6):937-943. doi: 10.1248/bpb.b18-00091.
In the development of drugs for intra-articular administration, sustained-release formulations are desirable because it is difficult to maintain the effect of conventional injections due to immediate drug leakage from the joint cavity. In this study, a sustained-release poly(lactic-co-glycolic acid) (PLGA) microsphere formulation for intra-articular administration containing indocyanine green (ICG) as a model drug was prepared to follow its fate after intra-articular administration in rats with a real-time in-vivo imaging system. ICG administered as an aqueous solution leaked from the joint cavity in a short time and was excreted outside the body within 1-3 d. However, ICG in the sustained-release formulation was retained in the joint cavity and released for 2 weeks. Next, a sustained-release formulation containing PLGA microspheres in a hyaluronic acid (HA) gel formulation was prepared. After gradual release in two stages, we could achieve sustained release for a longer period. It is considered that a combination formulation of PLGA microspheres and HA gel can significantly improve the sustained release of a drug administered into the knee joint.
在开发关节腔内给药的药物时，缓释制剂是理想的选择，因为由于药物从关节腔立即泄漏，难以维持传统注射的效果。在本研究中，制备了一种用于关节腔内给药的含有吲哚菁绿（ICG）作为模型药物的聚乳酸-乙醇酸共聚物（PLGA）微球缓释制剂，以便通过实时体内成像系统追踪其在大鼠关节腔内给药后的命运。以水溶液形式给药的ICG在短时间内从关节腔泄漏，并在1-3天内排出体外。然而，缓释制剂中的ICG保留在关节腔内并释放了2周。接下来，制备了一种在透明质酸（HA）凝胶制剂中含有PLGA微球的缓释制剂。经过两个阶段的逐步释放，我们可以实现更长时间的持续释放。认为PLGA微球和HA凝胶的组合制剂可以显著改善注入膝关节的药物的缓释效果。
