Pulmonary delivery of vancomycin dry powder aerosol to intubated rabbits

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Issue Date
2015-08-03Author
Sullivan, Bradley P.
El-Gendy, Nashwa
Kuehl, Christopher
Berkland, Cory J.
Publisher
American Chemical Society
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Rights
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/acs.molpharmaceut.5b00062.
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Show full item recordAbstract
TGX-221 is a potent, selective, and cell membrane permeable inhibitor of the PI3K p110β catalytic subunit. Recent studies showed that TGX-221 has anti-proliferative activity against PTEN-deficient tumor cell lines including prostate cancers. The objective of this study was to develop an encapsulation system for parenterally delivering TGX-221 to the target tissue through a prostate-specific membrane aptamer (PSMAa10) with little or no side effects. In this study, PEG-PCL micelles were formulated to encapsulate the drug, and a prodrug strategy was pursued to improve the stability of the carrier system. Fluorescence imaging studies demonstrated that the cellular uptake of both drug and nanoparticles were significantly improved by targeted micelles in a PSMA positive cell line. The area under the plasma concentration time curve of the micelle formulation in nude mice was 2.27-fold greater than the naked drug, and the drug clearance rate was 17.5-fold slower. These findings suggest a novel formulation approach for improving site-specific drug delivery of a molecular-targeted prostate cancer treatment.
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Citation
Sullivan, B. P., El-Gendy, N., Kuehl, C., & Berkland, C. (2015). Pulmonary delivery of vancomycin dry powder aerosol to intubated rabbits. Molecular Pharmaceutics, 12(8), 2665–2674. http://doi.org/10.1021/acs.molpharmaceut.5b00062
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