Paclitaxel loaded PEG5000–DSPE micelles as pulmonary delivery platform: Formulation characterization, tissue distribution, plasma pharmacokinetics, and toxicological evaluation

The objective of the present study was to evaluate the potential of paclitaxel loaded micelles fabricated from PEG5000–DSPE as a sustained release system following pulmonary delivery. PEG5000–DSPE micelles containing paclitaxel were prepared by solvent evaporation technique followed by investigation of in vitro release of paclitaxel in lung simulated fluid. Tissue distribution and plasma pharmacokinetics of the PEG–lipid micelles after intratracheal and intravenous administrations were investigated in addition to intratracheally administered taxol. Finally, toxicological profile of PEG5000–DSPE was investigated. Paclitaxel was successfully formulated in PEG–lipid micelles with encapsulation efficiency of 95%. The PEG–lipid micelles exhibited a sustained release behavior in the simulated lung fluid. Intratracheally administered polymeric micellar paclitaxel showed highest accumulation of paclitaxel in the lungs with AUC0–12 in lungs being 45-fold higher than intravenously administered formulation and 3-fold higher than intratracheally delivered taxol. Paclitaxel concentration in other non-targeted tissues and plasma were significantly lower as compared to other groups. Furthermore, toxicity studies showed no significant increase in levels of lung injury markers in PEG5000–DSPE treated group as compared to saline-treated group. PEG5000–DSPE micelles delivered intratracheally were able to sustain highest paclitaxel concentrations in lungs for long periods of time, thus apprehending their suitability as pulmonary drug carriers.

Graphical abstractPulmonary delivery of paclitaxel encapsulated in polymeric micelles resulted in slower drug release and sustained drug concentrations in lungs.Figure optionsDownload full-size imageDownload as PowerPoint slide