Noda Takehiro, Okuda Tomoyuki, Ban Kousuke, Mizuno Ryota, Tagami Tatsuaki, Ozeki Tetsuya, Okamoto Hirokazu
Graduate School of Pharmaceutical Sciences, Nagoya City University.
Faculty of Pharmacy, Meijo University.
Biol Pharm Bull. 2017 Jun 1;40(6):830-836. doi: 10.1248/bpb.b16-00950. Epub 2017 Jan 17.
In the development of a drug for intra-articular administration, a sustained-release formulation is desirable since it is difficult to sustain the effects of conventional injections due to fast drug leakage from the joint cavity. In this study, we prepared sustained release gel formulations for intra-articular administration containing indocyanine green (ICG) as a model drug to follow its fate after intra-articular administration in rats with in-vivo imaging system (IVIS). ICG administered as an aqueous solution leaked from the joint cavity in a short time and was excreted out of the body within a day. On the other hand, ICG in the sustained-release formulations was retained and released in the joint cavity for a week. Next, we prepared a sustained-release formulation with hyaluronic acid (HA) as the gel base containing a pain-relief drug (Drug A). We had administered it and other formulations into the rat knee where we injected bradykinin to evaluate their walking distance after 1 and 3 d. The effect of an aqueous solution of Drug A disappeared on day 3. The HA gel formulation without Drug A was more effective than the aqueous solution. The HA gel formulation with Drug A was the most effective; the walking distance was about 85% of the baseline on day 3. This study showed that the gel formulations were effective to sustain the release of a drug in the knee joint, and that the combination of a pain-relief drug with HA gel was effective to improve the mobility of the acute pain model rats.
在开发用于关节内给药的药物时，持续释放制剂是理想的，因为由于药物从关节腔快速渗漏，传统注射难以维持其效果。在本研究中，我们制备了用于关节内给药的含吲哚菁绿（ICG）的持续释放凝胶制剂，以作为模型药物，利用体内成像系统（IVIS）追踪其在大鼠关节内给药后的去向。以水溶液形式给药的ICG在短时间内从关节腔渗漏，并在一天内排出体外。另一方面，持续释放制剂中的ICG在关节腔内保留并释放了一周。接下来，我们制备了以透明质酸（HA）为凝胶基质、含有止痛药物（药物A）的持续释放制剂。我们将其和其他制剂注入大鼠膝关节，在其中注射缓激肽，以评估1天和3天后它们的行走距离。药物A水溶液的效果在第3天消失。不含药物A的HA凝胶制剂比水溶液更有效。含药物A的HA凝胶制剂最有效；第3天的行走距离约为基线的85%。本研究表明，凝胶制剂对于在膝关节中持续释放药物是有效的，并且止痛药物与HA凝胶的组合对于改善急性疼痛模型大鼠的活动能力是有效的。
