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Biodistribution and Pharmacokinetic Analysis of Paclitaxel and Ceramide Administered in Multifunctional Polymer-Blend Nanoparticles in Drug Resistant Breast Cancer Model
- Source :
- Molecular Pharmaceutics
- Publication Year :
- 2008
- Publisher :
- American Chemical Society, 2008.
-
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.
- Subjects :
- Drug
Ceramide
Biodistribution
Paclitaxel
Polymers
media_common.quotation_subject
Pharmaceutical Science
noncompartmental pharmacokinetics
Mice, Nude
Breast Neoplasms
02 engineering and technology
Pharmacology
Ceramides
Article
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Cell Line, Tumor
Drug Discovery
Animals
Humans
Tissue Distribution
ceramide
biodistribution
media_common
Chemistry
technology, industry, and agriculture
021001 nanoscience & nanotechnology
Xenograft Model Antitumor Assays
3. Good health
PLGA
Disease Models, Animal
polymer-blend nanoparticles
Apoptosis
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Multidrug resistant tumors
Molecular Medicine
Nanoparticles
Female
Polymer blend
0210 nano-technology
Combination drug
Subjects
Details
- Language :
- English
- ISSN :
- 15438392 and 15438384
- Volume :
- 5
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Molecular Pharmaceutics
- Accession number :
- edsair.doi.dedup.....a1a08203978281b1077c753be39ed86e