Preparation and in vitro characterization of lamivudine loaded nanoparticles prepared by acid and/or ester terminated PLGA for effective oral anti-retroviral therapy
Preparation and in vitro characterization of lamivudine loaded nanoparticles prepared by acid and/or ester terminated PLGA for effective oral anti-retroviral therapy
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DOI：
10.35333/jrp.2019.37
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发表时间：
2019-01-01
影响因子：
0.8
通讯作者：
Yurtdas Kirimlioglu, Gulsel
中科院分区：
文献类型：
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作者：
Ozturk, A. Alper;Yurtdas Kirimlioglu, Gulsel
本研究的目的是通过“双乳液溶剂蒸发”方法配制负载拉米夫定（LAM）的聚乳酸-乙醇酸（PLGA）纳米颗粒（NP）制剂，用于口服给药。本研究使用分子量相似但有两种不同化学端基（酸或酯封端）的 PLGA 来比较 NP 表征的效果。通过粒径 (PS)、多分散指数 (PDI)、zeta 电位、包封率 (EE%)、溶解和释放动力学研究来表征纳米颗粒，并最终确定最佳配方。发现所选的最佳配方（B 编码）的 PS 为 221.0 +/- 0.7 nm，PDI 较低为 0.104 +/- 0.014。最佳 NP 制剂的药物 EE % 为 30.280%+/- 0.600。在磷酸盐缓冲液（pH 6.8）中检查了负载 LAM 的 NP 的体外释放。负载 LAM 的 NP 的体外释放研究表明，其释放时间长达 144 小时，从而证实了纳米结构的表现。 Higuchi 和 Korsmeyer-Peppas 动力学模型被发现最适合 PLGA-NP 中 LAM 的释放。最佳配方在24小时胃肠道稳定性研究中是稳定的，并且通过DSC、FT-IR和(HNMR)-H-1分析对NP结构进行了表征。可以得出结论，负载 LAM 的 NP 似乎是一种有前途的抗逆转录病毒治疗口服缓释药物递送系统。最后，体外表征和释放数据证明了通过 PLGA-NP 制剂提高 LAM 生物利用度的可能性，并且还阐明了本研究中使用的聚合物对制剂特性的影响
The aim of this study was to formulate Lamivudine (LAM) loaded poly lactic-co-glycolic acid (PLGA) nanoparticle (NP) formulations by 'double emulsion solvent evaporation' method for oral administration. PLGA with similar molecular weight but two different chemical end-groups (acid or ester terminated), were used in this study to to compare the effects in the characterization of NPs. Particle size (PS), polydispersity index (PDI), zeta potential, entrapment efficiency (EE%), dissolution and release kinetic studies were carried out for the characterization of NPs and finally for determining the optimum formulation. The selected optimum formulation (B coded) was found to have a PS of 221.0 +/- 0.7 nm and a low PDI as 0.104 +/- 0.014. Drug EE % of optimal NP formulation was found as 30.280%+/- 0.600. In vitro release of LAM loaded NPs were examined in phosphate buffer (pH 6.8). In vitro release studies of LAM-loaded NPs showed an extended release up to 144 hours, thus the demonstration of nanostructures was confirmed. Higuchi and Korsmeyer-Peppas kinetic model was found to fit best for LAM release from PLGA-NPs. The optimum formulation was stable in the 24-hour gastrointestinal stability study and the NP structure was characterized by DSC, FT-IR and (HNMR)-H-1 analyzes. It could be concluded that LAM loaded NPs seem to be a promising extended release drug delivery system for oral administration in antiretroviral therapy. Lastly, in vitro characterization and release data demonstrated the possibility of improved bioavailability of LAM by PLGA-NP formulation and the effect of polymers used in this study on formulation characteristics were also elucidated