Abstract Poly( d , l -lactic-co-glycolic acid), or PLGA, is the most frequently used biodegradable and biocompatible polymer in preparation of nanoparticles for biomedical applications. In this work nanoparticles composed of PLGA were prepared to produce nanocarriers for a platinum-based antitumoral drug: carboplatin. The carboplatin-loaded PLGA nanoparticles were obtained by nanoprecipitation method, using TPGS (D-α-tocopheryl polyethylene glycol succinate) as stabilizer and acetone as organic phase. In order to improve the delivery of carboplatin to cancer cells, folic acid-conjugated chitosan-coated (FA-CS) PLGA nanoparticles were also prepared, using 22 factorial design with center point for unmodified and surface modified nanoparticles. For PLGA nanoparticles, the results showed that mean particle size is dependent of time, amplitude of sonication, volume and concentration of TPGS aqueous solution (according to a linear model), while PDI and zeta potential are constants. The optimized formulation (121.0 nm, PDI = 0.120 and −34.0 mV) was stable over a period of 60 days when stored at 10 °C, with entrapment efficiency (EE) = 5%, drug loading = 0.37% and nanoparticle yield = 77%. Also, it was possible to improve these parameters (EE = 39.5%, drug loading = 2.6% and yield = 91%) by reduction of dialysis (24–2 h) and acetone evaporation (24–1 h) time. For surface modified PLGA nanoparticles, mean particle size and PDI are dependent of stirring time and concentration of FA-CS solution (according to a quadratic model), while zeta potential is also dependent of these factors but according to a linear model. The optimal formulation showed particles with size of 178.0 nm, PDI = 0.20, zeta potential = 46.0 mV, EE = 35.5%, drug loading = 1.8% and nanoparticle yield = 92%. Encapsulation of carboplatin was confirmed by UV–Vis spectroscopy using a derivatization technique with orto-phenylenediamine. In conclusion, the results obtained in this work demonstrated that formulation variables can be explored to obtain the optimal preparation conditions of PLGA nanoparticles.

中文翻译：

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用于卡铂包封的叶酸偶联壳聚糖功能化 PLGA 纳米颗粒的制备

摘要 聚（d，l-乳酸-乙醇酸共聚物）或 PLGA 是制备用于生物医学应用的纳米颗粒中最常用的可生物降解和生物相容性聚合物。在这项工作中，制备了由 PLGA 组成的纳米颗粒，以生产用于铂类抗肿瘤药物卡铂的纳米载体。以TPGS（D-α-生育酚聚乙二醇琥珀酸酯）为稳定剂，丙酮为有机相，通过纳米沉淀法制备了载有卡铂的PLGA纳米颗粒。为了改善卡铂向癌细胞的递送，还制备了叶酸偶联壳聚糖涂层 (FA-CS) PLGA 纳米粒子，使用 22 因子设计，中心点为未修饰和表面修饰的纳米粒子。对于 PLGA 纳米粒子，结果表明平均粒径取决于时间，超声振幅、TPGS 水溶液的体积和浓度（根据线性模型），而 PDI 和 zeta 电位是常数。优化后的配方（121.0 nm，PDI = 0.120 和 -34.0 mV）在 10 °C 下可稳定保存 60 天，包封率 (EE) = 5%，载药量 = 0.37%，纳米粒子产率 = 77 %。此外，还可以通过减少透析（24-2 小时）和丙酮蒸发（24-1 小时）时间来改善这些参数（EE = 39.5%，载药量 = 2.6% 和产率 = 91%）。对于表面改性的 PLGA 纳米粒子，平均粒径和 PDI 取决于搅拌时间和 FA-CS 溶液的浓度（根据二次模型），而 zeta 电位也取决于这些因素，但根据线性模型。最佳配方显示颗粒大小为 178.0 nm，PDI = 0.20，zeta 电位 = 46.0 mV，EE = 35.5%，载药量 = 1.8%，纳米粒子产率 = 92%。使用邻苯二胺的衍生化技术，通过紫外-可见光谱法证实了卡铂的包封。总之，在这项工作中获得的结果表明，可以探索配方变量以获得 PLGA 纳米颗粒的最佳制备条件。