Marked effects of combined TPGS and PVA emulsifiers in the fabrication of etoposide-loaded PLGA-PEG nanoparticles: In vitro and in vivo evaluation

作者：Saadati Roonak; Dadashzadeh Simin^*

来源：International Journal of Pharmaceutics, 2014, 464(1-2): 135-144.

DOI：10.1016/j.ijpharm.2014.01.014

• PLGA-PEG
• TPGS
• Nanoparticles
• Etoposide
• Dual emulsifiers
• Pharmacokinetics

The purpose of this study was to investigate the effect of D-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) alone or in combination with other emulsifiers in the fabrication of etoposide-loaded PLGA-PEG nanoparticles for in vivo applications.
Nanoparticles were prepared by nanoprecipitation or single-emulsion solvent evaporation method using TPGS alone or in combination with other surfactants. These nanoparticles were fully characterized by different techniques. For nanoprecipitation preparations, by adding 0.1% TPGS to polyvinyl alcohol in the aqueous phase, encapsulation efficiency markedly increased (up to 82%); moreover, drug release was readily controlled up to 3 days. Regarding emulsion solvent evaporation method, the highest encapsulation efficiency was obtained for nanoparticles emulsified with polyvinyl alcohol or TPGS; however, the burst release was high. When the combination of TPGS and polyvinyl alcohol was applied a marked increase in encapsulation efficiency (similar to 90%) was observed and the drug release was extended to more than one week.
Pharmacokinetic measurements showed that the optimum formulation generated 14.4 times higher AUC and lasted 5.1 times longer when compared to free drug. Overall, using TPGS in combination with polyvinyl alcohol as an emulsifier in preparing etoposide loaded PLGA-PEG nanoparticles markedly increased the encapsulation efficiency, sustained drug release and resulted in nanoparticles with noticeable sustainable in vivo disposition.

• 出版日期2014-4-10