Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Tecnología Farmacéutica I, Buenos Aires, Argentina; Universidad de Buenos Aires, Instituto de Tecnología Farmacéutica y Biofarmacia (InTecFyB), Buenos Aires, Argentina.
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Tecnología Farmacéutica I, Buenos Aires, Argentina; Universidad de Buenos Aires, Instituto de Tecnología Farmacéutica y Biofarmacia (InTecFyB), Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.
Int J Pharm. 2024 Feb 15;651:123734. doi: 10.1016/j.ijpharm.2023.123734. Epub 2023 Dec 22.
The present investigation was focused on the development of Soluplus®-based nanomicelles (NMs) (10 % w/v) loaded with Efavirenz (EFV) (5 mg/mL) and Curcumin (natural bio-enhancer) (CUR) (5, 10 and 15 mg/mL) to improve the oral bioavalability of EFV. Micellar formulations were obtained employing an acetone-diffusion technique. Apparent aqueous solubility was increased up to ∼1250-fold and 25,000-fold for EFV and CUR, respectively. Drug-loaded nanoformulations showed an excellent colloidal stability with unimodal size distribution and PDI values < 0.30. In vitro drug release was 41.5 % (EFV) and 2.6 % (CUR) from EFV-CUR-NMs over 6 h in simulated gastrointestinal fluids. EFV-CUR-loaded NMs resulted as safe nanoformulations according to the in vitro cytocompatibility assays in Caco-2 cells. Furthermore, CUR bio-enhancer activity was demonstrated for those nanoformulations. A CUR concentration of 15 mg/mL produced a significant (p < 0.05) increment (2.64-fold) of relative EFV oral bioavailability. Finally, the active role of the lymphatic system in the absorption process of EFV, after its oral administration was assessed in a comparative pharmacokinetic study in presence and absence of cycloheximide, a lymphatic transport inhibitor. Overall our EFV-CUR-NMs denoted their potential as a novel nanotechnological platform, representing a step towards an optimized "nano-sized" therapy for AIDS patients.
本研究集中于开发基于 Soluplus®的纳米胶束（NMs）（10％w/v），负载依非韦伦（EFV）（5mg/mL）和姜黄素（天然生物增强剂）（CUR）（5、10 和 15mg/mL），以提高 EFV 的口服生物利用度。采用丙酮扩散技术获得胶束制剂。EFV 和 CUR 的表观水溶解度分别提高了约 1250 倍和 25000 倍。载药纳米制剂表现出优异的胶体稳定性，具有单峰粒径分布和 PDI 值<0.30。在模拟胃肠道液中，EFV-CUR-NMs 在 6 小时内释放 41.5％（EFV）和 2.6％（CUR）的药物。根据 Caco-2 细胞中的体外细胞相容性试验，EFV-CUR 载药纳米制剂被证明是安全的纳米制剂。此外，还证明了 CUR 生物增强剂活性。CUR 浓度为 15mg/mL 时，可显著（p<0.05）提高 EFV 的相对口服生物利用度（2.64 倍）。最后，在环已酰亚胺（一种淋巴转运抑制剂）存在和不存在的情况下，在口服给药后评估了 EFV 吸收过程中淋巴系统的主动作用。总的来说，我们的 EFV-CUR-NMs 表明它们具有作为新型纳米技术平台的潜力，代表了向艾滋病患者优化“纳米级”治疗的一步。
