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.
Highlights
Fluticasone propionate (FP) is one of the most potent inhaled corticosteroids (ICS) that is commonly prescribed as the first line therapy for the asthma management [1,2,3]
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)
Summary
Fluticasone propionate (FP) is one of the most potent inhaled corticosteroids (ICS) that is commonly prescribed as the first line therapy for the asthma management [1,2,3]. A further goal is to maximize lung residence time; mucus-penetrating particles must be designed by realizing nanoparticles possessing a coating able to minimize adhesive interactions with mucin fibers, penetrating readily into the pulmonary mucus layer [4,5,6]. This strategy could be targeted by the attachment of hydrophilic uncharged polymers, like polyethylenglycol (PEG) to drugs, proteins, and particles, which seems to reduce interactions with sialic acid, a major component of mucus [7,8,9]. Popov and coworkers [4] realized FP-loaded mucus-penetrating nanoparticles and, by in vivo experiments, demonstrated that the pulmonary administration achieved a higher local exposure to FP in lungs of rodents when compared to free drug, leading to a significant extension of the anti-inflammatory effect of FP in a rat lung inflammation model as compared to a non-encapsulated FP control
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