Laboratorio de Investigación y Posgrado en Tecnología Farmacéutica, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Cuautitlán Izcalli, Estado de México, México.
Int J Nanomedicine. 2013;8:2141-51. doi: 10.2147/IJN.S44482. Epub 2013 Jun 10.
A biodegradable polymeric system is proposed for formulating peptides and proteins. The systems were assembled through the adsorption of biodegradable polymeric nanoparticles onto porous, biodegradable microspheres by an adsorption/infiltration process with the use of an immersion method. The peptide drug is not involved in the manufacturing of the nanoparticles or in obtaining the microspheres; thus, contact with the organic solvent, interfaces, and shear forces required for the process are prevented during drug loading. Leuprolide acetate was used as the model peptide, and poly(d,l-lactide-co-glycolide) (PLGA) was used as the biodegradable polymer. Leuprolide was adsorbed onto different amounts of PLGA nanoparticles (25 mg/mL, 50 mg/mL, 75 mg/mL, and 100 mg/mL) in a first stage; then, these were infiltrated into porous PLGA microspheres (100 mg) by dipping the structures into a microsphere suspension. In this way, the leuprolide was adsorbed onto both surfaces (ie, nanoparticles and microspheres). Scanning electron microscopy studies revealed the formation of a nanoparticle film on the porous microsphere surface that becomes more continuous as the amount of infiltrated nanoparticles increases. The adsorption efficiency and release rate are dependent on the amount of adsorbed nanoparticles. As expected, a greater adsorption efficiency (95%) and a slower release rate were seen (20% of released leuprolide in 12 hours) when a larger amount of nanoparticles was adsorbed (100 mg/mL of nanoparticles). Leuprolide acetate begins to be released immediately when there are no infiltrated nanoparticles, and 90% of the peptide is released in the first 12 hours. In contrast, the systems assembled in this study released less than 44% of the loaded drug during the same period of time. The observed release profiles denoted a Fickian diffusion that fit Higuchi's model (t(1/2)). The manufacturing process presented here may be useful as a potential alternative for formulating injectable depots for sensitive hydrophilic drugs such as peptides and proteins, among others.
提出了一种可生物降解的聚合物系统来制备肽和蛋白质。该系统通过吸附可生物降解的聚合物纳米粒子到多孔、可生物降解的微球上来组装，通过使用浸渍法进行吸附/渗透过程。肽药物不参与纳米粒子的制造或微球的获得；因此，在药物加载过程中，避免了与有机溶剂、界面和剪切力的接触。醋酸亮丙瑞林被用作模型肽，聚（D，L-丙交酯-共-乙交酯）（PLGA）被用作可生物降解的聚合物。亮丙瑞林以不同的量吸附到不同量的 PLGA 纳米粒子（25mg/ml、50mg/ml、75mg/ml 和 100mg/ml）上；然后，将这些结构浸入微球悬浮液中，将其渗透到多孔 PLGA 微球（100mg）中。这样，亮丙瑞林就被吸附到了两个表面（即纳米粒子和微球）上。扫描电子显微镜研究表明，在多孔微球表面形成了一层纳米粒子膜，随着渗透的纳米粒子数量的增加，膜变得更加连续。吸附效率和释放速率取决于吸附的纳米粒子的数量。正如预期的那样，当吸附的纳米粒子数量较大（100mg/ml 的纳米粒子）时，观察到更高的吸附效率（95%）和更慢的释放速率（12 小时内释放亮丙瑞林的 20%）。当没有渗透的纳米粒子时，亮丙瑞林醋酸盐立即开始释放，90%的肽在最初的 12 小时内释放。相比之下，在同一时间段内，本研究中组装的系统释放的载药量不到 44%。观察到的释放曲线表示出符合 Higuchi 模型（t(1/2)）的菲克扩散。这里提出的制造工艺可能对制备其他敏感亲水性药物（如肽和蛋白质）的可注射储存库具有潜在的应用价值。
