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Paclitaxel loaded PEG(5000)-DSPE micelles as pulmonary delivery platform: formulation characterization, tissue distribution, plasma pharmacokinetics, and toxicological evaluation.
- Source :
-
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2011 Oct; Vol. 79 (2), pp. 276-84. Date of Electronic Publication: 2011 May 07. - Publication Year :
- 2011
-
Abstract
- The objective of the present study was to evaluate the potential of paclitaxel loaded micelles fabricated from PEG(5000)-DSPE as a sustained release system following pulmonary delivery. PEG(5000)-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 PEG(5000)-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 AUC(0-12) 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 PEG(5000)-DSPE treated group as compared to saline-treated group. PEG(5000)-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.<br /> (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents, Phytogenic administration & dosage
Antineoplastic Agents, Phytogenic chemistry
Antineoplastic Agents, Phytogenic toxicity
Chemistry, Pharmaceutical methods
Delayed-Action Preparations
Drug Carriers administration & dosage
Drug Carriers chemistry
Drug Carriers toxicity
Drug Delivery Systems adverse effects
Drug Delivery Systems methods
Lung drug effects
Male
Paclitaxel administration & dosage
Paclitaxel chemistry
Phosphatidylethanolamines administration & dosage
Phosphatidylethanolamines chemistry
Phosphatidylethanolamines toxicity
Polyethylene Glycols administration & dosage
Polyethylene Glycols chemistry
Polyethylene Glycols toxicity
Rats
Rats, Sprague-Dawley
Tissue Distribution
Trachea
Antineoplastic Agents, Phytogenic pharmacokinetics
Drug Carriers pharmacokinetics
Lung metabolism
Micelles
Paclitaxel pharmacokinetics
Phosphatidylethanolamines pharmacokinetics
Polyethylene Glycols pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3441
- Volume :
- 79
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
- Publication Type :
- Academic Journal
- Accession number :
- 21575719
- Full Text :
- https://doi.org/10.1016/j.ejpb.2011.04.017