Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles-ULB, Campus de la Plaine, BC, B-1050 Brussels, Belgium.
Int J Pharm. 2013 Jul 15;451(1-2):95-103. doi: 10.1016/j.ijpharm.2013.04.079. Epub 2013 May 4.
Osteoarthritis is characterized by slow degenerative processes in the articular cartilage within synovial joints. It could be interesting to develop a sustained-release formulation that could be effective on both pain/inflammation and restoration of mechanical integrity of the joint. Recently, an injectable system based on glycerol monooleate (GMO), containing clonidine as a model hydrophilic analgesic/anti-inflammatory drug and hyaluronic acid as a viscoelastic scaffold, showed promising potential as a biodegradable and biocompatible preparation to sustain the drug activity. However, drug release from the system is relatively fast (complete within 1 week) and the underlying drug release mechanisms not fully understood. The aims of this study were: (i) to significantly improve this type of local controlled drug delivery system by further sustaining clonidine release, and (ii) to elucidate the underlying mass transport mechanisms. The addition of FDA-approved inactive ingredients such as sodium oleate or purified soybean oil was found to be highly effective. The release rate could be substantially reduced (e.g., 50% release after 10 days), due to the increased hydrophobicity of the systems, resulting in slower and reduced water uptake and reduced drug mobility. Interestingly, Fick's second law of diffusion could be used to quantitatively describe drug release.
骨关节炎的特征是滑液关节内的关节软骨的缓慢退行性过程。开发一种能够有效缓解疼痛/炎症并恢复关节机械完整性的缓释制剂可能很有趣。最近，一种基于甘油单油酸酯（GMO）的可注射系统，含有可乐定作为模型亲水性镇痛药/抗炎药和透明质酸作为粘弹性支架，作为一种可生物降解和生物相容的制剂，具有很大的潜力来维持药物活性。然而，该系统的药物释放速度相对较快（在 1 周内完全释放），并且其潜在的药物释放机制尚未完全阐明。本研究的目的是：（i）通过进一步延长可乐定的释放来显著改善这种局部控制药物输送系统，（ii）阐明潜在的质量传递机制。发现添加经 FDA 批准的非活性成分，如油酸钠或精制大豆油，非常有效。由于系统疏水性增加，导致水吸收速度减慢、减少，药物迁移率降低，因此释放速率可以大大降低（例如，10 天后 50%释放）。有趣的是，可以使用菲克第二扩散定律来定量描述药物释放。
