Improving the therapeutic efficacy of prilocaine by PLGA microparticles: Preparation, characterization and in vivo evaluation
Improving the therapeutic efficacy of prilocaine by PLGA microparticles: Preparation, characterization and in vivo evaluation
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DOI：
10.1016/j.ijpharm.2018.05.054
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发表时间：
2018-08-25
影响因子：
5.8
通讯作者：
Mannelli, Lorenzo Di Cesare
中科院分区：
文献类型：
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作者：
Bragagni, Marco;Esther Gil-Alegre, Maria;Mannelli, Lorenzo Di Cesare
已经开发了基于聚（乳酸-共-乙醇酸）聚合物（PLGA）微粒的递送系统，用于以其游离碱形式的局部麻醉剂丙胺卡因的胃肠外给药。无药和载药微粒，通过双乳液蒸发法制备，其特征在于平均尺寸通过激光衍射分析，而它们的形态通过扫描电子显微镜进行了研究。制备技术允许获得直径约25 μ m的均匀微粒，适合于皮下给药。通过直接和间接方法测定的包封率为约36- 38%。采用差示扫描量热法表征原材料的固态，评估药物-聚合物相容性和相容性，并突出显示制备方法诱导的组分可能的修饰。体外释药研究表明，缓释曲线，约80%的药物释放后的第一个24小时。通过皮肤干肌反射试验，评价了该制剂在大鼠体内的麻醉作用。与等效剂量的盐酸丙胺卡因水溶液相比，给予丙胺卡因碱作为PLGA微粒可以显著增强动物模型中麻醉作用的程度（AUC增加60%）和持续时间（增加100%）。
A delivery system based on poly(lactic-co-glycolic acid) polymer (PLGA) microparticles has been developed for parenteral administration of the local anesthetic prilocaine in its free base form. Both drug-free and drug-loaded microparticles, prepared by a double-emulsion-evaporation method, were characterized for mean size by Laser Diffraction Analysis, while their morphology was investigated by scanning electron microscopy. The preparation technique allowed obtainment of homogeneous microparticles of about 25 mu m diameter, suitable for subcutaneous administration. The encapsulation efficiency, determined by both direct and indirect methods, was around 36-38%. Differential Scanning Calorimetry was used to characterize the solid state of the raw materials, assess drug-polymer compatibility and miscibility and highlight possible modifications of the components induced by the preparation method. In vitro release studies showed a sustained release profile, with about 80% of drug released after the first 24 h. The anesthetic effect of the formulation was evaluated in vivo on rats, according to the test of cutaneous trunci muscle reflex. Administration of prilocaine base as PLGA microparticles allowed to significantly enhance both extent (60% AUC increase) and duration (100% increase) of the anesthetic effect in the animal model, in comparison with the equivalent dose of prilocaine hydrochloride aqueous solution.