Biodistribution and pharmacokinetic analysis of Paclitaxel and ceramide administered in multifunctional polymer-blend nanoparticles in drug resistant breast cancer model.

Abstract	In this study, we have investigated the biodistribution and pharmacokinetic analysis of paclitaxel (PTX) and the apoptotic signaling molecule, C6-ceramide (CER), when administered in a multifunctional polymer-blend nanoparticle formulation to female nude mice bearing an orthotopic drug sensitive MCF7 and multidrug resistant MCF7 TR (MDR-1 positive) human breast adenocarcinoma. A polymer-blend nanoparticle system was engineered to incorporate temporally controlled sequential release of the combination drug payload. Hereby, PTX was encapsulated in the pH-responsive rapid releasing polymer, poly(beta-amino ester) (PbAE), while CER was present in the slow releasing polymer, poly(D,L-lactide-co-glycolide) (PLGA) within these blend nanoparticles. When particle formulations were administered intravenously to MCF7 and MCF7 TR tumor bearing mice, higher concentrations of PTX were found in the blood due to longer retention time and an enhanced tumor accumulation relative to administration of free drug. In addition, the PLGA/PbAE blend nanoparticles were effective in enhancing the residence time of both drugs at the tumor site by reducing systemic clearance. Overall, these results are highly encouraging for development of multifunctional polymer-blend nanoparticle formulations that can be used for temporal-controlled administration of two drugs from a single formulation.
Authors	Lilian E van Vlerken, Zhenfeng Duan, Steven R Little, Michael V Seiden, Mansoor M Amiji
Journal	Molecular pharmaceutics (Mol Pharm) 2008 Jul-Aug Vol. 5 Issue 4 Pg. 516-26 ISSN: 1543-8384 [Print] United States
PMID	18616278 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References	Ceramides Polymers Paclitaxel
Topics	Animals Breast Neoplasms (pathology) Cell Line, Tumor Ceramides (administration & dosage, pharmacokinetics, therapeutic use) Disease Models, Animal Drug Resistance, Neoplasm (drug effects) Female Humans Mice Mice, Nude Nanoparticles (chemistry, therapeutic use) Paclitaxel (administration & dosage, pharmacokinetics, therapeutic use) Polymers (chemistry) Tissue Distribution Xenograft Model Antitumor Assays

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