Cagnon Marie-Emérentienne, Curia Silvio, Serindoux Juliette, Cros Jean-Manuel, Ng Feifei, Lopez-Noriega Adolfo
MedinCell SA, 3 Rue des Frères Lumière, 34830 Jacou, France.
Pharmaceutics. 2021 Apr 22;13(5):605. doi: 10.3390/pharmaceutics13050605.
This article describes the utilization of (methoxy)poly(ethylene glycol)--poly(1,3-trimethylene carbonate) ((m)PEG-PTMC) diblock and triblock copolymers for the formulation of in situ forming depot long-acting injectables by solvent exchange. The results shown in this manuscript demonstrate that it is possible to achieve long-term drug deliveries from suspension formulations prepared with these copolymers, with release durations up to several months in vitro. The utilization of copolymers with different PEG and PTMC molecular weights affords to modulate the release profile and duration. A pharmacokinetic study in rats with meloxicam confirmed the feasibility of achieving at least 28 days of sustained delivery by using this technology while showing good local tolerability in the subcutaneous environment. The characterization of the depots at the end of the in vivo study suggests that the rapid phase exchange upon administration and the surface erosion of the resulting depots are driving the delivery kinetics from suspension formulations. Due to the widely accepted utilization of meloxicam as an analgesic drug for animal care, the results shown in this article are of special interest for the development of veterinary products aiming at a very long-term sustained delivery of this therapeutic molecule.
本文描述了利用（甲氧基）聚（乙二醇）-聚（1,3-三亚甲基碳酸酯）（（m）PEG-PTMC）二嵌段和三嵌段共聚物，通过溶剂交换来制备原位形成长效注射剂的储库。本手稿中所示结果表明，用这些共聚物制备的混悬剂有可能实现长期药物递送，体外释放持续时间可达数月。使用具有不同PEG和PTMC分子量的共聚物能够调节释放曲线和持续时间。对大鼠进行的美洛昔康药代动力学研究证实，使用该技术可实现至少28天的持续递送，同时在皮下环境中显示出良好的局部耐受性。体内研究结束时对储库的表征表明，给药时的快速相交换以及所得储库的表面侵蚀推动了混悬剂的递送动力学。由于美洛昔康作为动物护理用镇痛药的广泛应用，本文所示结果对于旨在实现该治疗分子非常长期持续递送的兽用产品开发具有特别的意义。
