Yessentayeva Nazgul A, Galiyeva Aldana R, Daribay Arailym T, Sadyrbekov Daniyar T, Moustafine Rouslan I, Tazhbayev Yerkeblan M
Chemistry Department, Karaganda Buketov University, Karaganda 100028, Kazakhstan.
Institute of Pharmacy, Kazan State Medical University, Kazan 420126, Russia.
Polymers (Basel). 2024 Aug 30;16(17):2466. doi: 10.3390/polym16172466.
Despite the large number of works on the synthesis of polylactide-co-glycolide (PLGA) nanoparticles (NP) loaded with antituberculosis drugs, the data on the influence of various factors on the final characteristics of the complexes are quite contradictory. In the present study, a comprehensive analysis of the effect of multiple factors, including the molecular weight of PLGA, on the size and stability of nanoparticles, as well as the loading efficiency and release of the antituberculosis drug rifampicin (RIF), was carried out. Emulsification was carried out using different surfactants (polyvinyl alcohol, Tween 80 and Pluronic F127), different aqueous-to-organic phase ratios, and different solvents (dichloromethane, dimethyl sulfoxide, ethyl acetate). In this research, the PLGA nanoemulsion formation process was accompanied by ultrasonic dispersion, at different frequencies and durations of homogenization. The use of the central composite design method made it possible to select optimal conditions for the preparation of PLGA-RIF NPs (particle size 223 ± 2 nm, loading efficiency 67 ± 1%, nanoparticles yield 47 ± 2%). The release of rifampicin from PLGA NPs was studied for the first time using the flow cell method and vertical diffusion method on Franz cells at different pH levels, simulating the gastrointestinal tract. For the purpose of the possible inhalation administration of rifampicin immobilized in PLGA NPs, their mucoadhesion to mucin was studied, and a high degree of adhesion of polymeric nanoparticles to the mucosa was shown (more than 40% within 4 h). In the example of strain H37Rv in vitro, the sensitivity of to PLGA-RIF NPs was proven by the complete inhibition of their growth.
尽管有大量关于负载抗结核药物的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒（NP）合成的研究，但关于各种因素对复合物最终特性影响的数据却相当矛盾。在本研究中，对包括PLGA分子量在内的多种因素对纳米颗粒大小和稳定性以及抗结核药物利福平（RIF）的负载效率和释放的影响进行了全面分析。使用不同的表面活性剂（聚乙烯醇、吐温80和普朗尼克F127）、不同的水相-有机相比以及不同的溶剂（二氯甲烷、二甲基亚砜、乙酸乙酯）进行乳化。在本研究中，PLGA纳米乳液的形成过程伴随着超声分散，采用了不同的频率和均质化持续时间。使用中心复合设计方法能够选择制备PLGA-RIF NPs的最佳条件（粒径223±2nm，负载效率67±1%，纳米颗粒产率47±2%）。首次使用流通池法和垂直扩散法在不同pH水平的Franz细胞上模拟胃肠道研究了利福平从PLGA NPs中的释放。为了使固定在PLGA NPs中的利福平有可能通过吸入给药，研究了它们对粘蛋白的粘膜粘附性，结果表明聚合物纳米颗粒对粘膜具有高度粘附性（4小时内超过40%）。在体外菌株H37Rv的例子中，通过完全抑制其生长证明了其对PLGA-RIF NPs的敏感性。
