Polyaspartamide-Based Nanoparticles Loaded with Fluticasone Propionate and the In Vitro Evaluation towards Cigarette Smoke Effects

Abstract

This paper describes the evaluation of polymeric nanoparticles (NPs) as a potential carrier for lung administration of fluticasone propionate (FP). The chosen polymeric material to produce NPs was a copolymer based on α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) whose backbone was derivatised with different molecules, such as poly(lactic acid) (PLA) and polyethylenglycol (PEG). The chosen method to produce NPs from PHEA-PLA-PEG2000 was the method based on high-pressure homogenization and subsequent solvent evaporation by adding Pluronic F68 during the process and trehalose before lyophilisation. Obtained colloidal FP-loaded NPs showed a slightly negative surface charge and nanometric dimensions that are maintained after storage for one year at −20 °C and 5 °C. The FP loading was about 2.9 wt % and the drug was slowly released in simulated lung fluid. Moreover, the obtained NPs, containing the drug or not, were biocompatible and did not induce cell necrosis and cell apoptosis on bronchial epithelial cells (16-HBE). Further in vitro testing on cigarette smoke extract (CSE)-stimulated 16-HBE revealed that FP-loaded NPs were able to reduce the survivin expression, while either free FP or empty NPs were not able to significantly reduce this effect.

Keywords

• α,β-poly-(N-2-hydroxyethyl)-
• d,%22%2C%22default_operator%22%3A%22AND%22%7D%7D%7D"> ">d,
• l-aspartamide (PHEA)%22%2C%22default_operator%22%3A%22AND%22%7D%7D%7D"> ">l-aspartamide (PHEA)
• poly(lactic acid) (PLA)
• poly(ethylene glycol) (PEG)
• polymeric nanoparticles
• fluticasone propionate (FP)