Departamento de Farmácia, Universidade Estadual do Centro-Oeste/UNICENTRO, Guarapuava, PR 85040-080, Brazil.
Int J Pharm. 2010 Aug 16;395(1-2):266-71. doi: 10.1016/j.ijpharm.2010.05.020. Epub 2010 May 24.
This study describes the preparation and evaluation of biodegradable poly(l-lactide) (PLA) and poly(l-lactide)-poly(ethylene glycol) (PLA-PEG) blend nanoparticles containing zidovudine as model drug. The prepared nanoparticles were characterized in terms of size, zeta potential, morphology and drug entrapment efficiency. The pharmacokinetics of zidovudine following intranasal administration in mice was assessed. The results showed that although PLA and blend nanoparticles had the same morphology, the particle size and zeta potential were changed by the PEG. The drug entrapment efficiency was increased by PEG presence. The pharmacokinetic study showed that all the nanoparticles were able to sustain zidovudine delivery over time, but greater efficiency was obtained with PLA-PEG blend nanoparticles, whose T(max) was twice that of PLA nanoparticles. The PLA and PLA-PEG nanoparticles formulations increased the zidovudine mean half-life by approximately 5.5 and 7h, respectively, compared to zidovudine aqueous solution. The relative bioavailability of zidovudine-loaded PLA-PEG blend nanoparticles was 2.7, relative to zidovudine-loaded PLA nanoparticles and 1.3 relative to aqueous solution formulation. Thus, the PLA nanoparticles were unable to increase the zidovudine bioavailability compared to aqueous solution formulation. The results obtained in this study indicate the potential of the PLA-PEG blend nanoparticles as carriers for zidovudine delivery by the intranasal route.
本研究描述了载有齐多夫定（作为模型药物）的可生物降解聚（L-丙交酯）（PLA）和聚（L-丙交酯）-聚（乙二醇）（PLA-PEG）共混纳米粒子的制备和评价。所制备的纳米粒子在粒径、Zeta 电位、形态和药物包封效率方面进行了表征。评估了齐多夫定经鼻腔给药在小鼠体内的药代动力学。结果表明，尽管 PLA 和共混纳米粒子具有相同的形态，但 PEG 的存在改变了粒子的粒径和 Zeta 电位。PEG 的存在增加了药物包封效率。药代动力学研究表明，所有纳米粒子都能够随着时间的推移持续释放齐多夫定，但 PLA-PEG 共混纳米粒子的效率更高，其 T(max)是 PLA 纳米粒子的两倍。与齐多夫定水溶液相比，PLA 和 PLA-PEG 纳米粒子制剂分别将齐多夫定的平均半衰期延长了约 5.5 和 7 小时。与 PLA 载药纳米粒子相比，载药 PLA-PEG 共混纳米粒子的齐多夫定相对生物利用度为 2.7，与水溶液制剂相比为 1.3。因此，与水溶液制剂相比，PLA 纳米粒子不能提高齐多夫定的生物利用度。本研究结果表明，PLA-PEG 共混纳米粒子作为齐多夫定经鼻腔给药的载体具有潜力。
