Polylactide-Based Paclitaxel-Loaded Nanoparticles Fabricated by Dispersion Polymerization: Characterization, Evaluation in Cancer Cell Lines, and Preliminary Biodistribution Studies

The macromonomer method was used to prepare cross-linked, paclitaxel-loaded polylactide (PLA)–polyethylene glycol (stealth) nanoparticles using free-radical dispersion polymerization. The method can facilitate the attachment of other molecules to the nanoparticle surface to make it multifunctional....

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2014-08, Vol.103 (8), p.2546-2555
Main Authors: Adesina, Simeon K., Holly, Alesia, Kramer-Marek, Gabriela, Capala, Jacek, Akala, Emmanuel O.
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents, Phytogenic - administration & dosage
Antineoplastic Agents, Phytogenic - pharmacokinetics
Antineoplastic Agents, Phytogenic - pharmacology
biodegradable polymers
Breast - drug effects
Breast - pathology
Breast Neoplasms - drug therapy
Breast Neoplasms - pathology
cell culture
Cell Line, Tumor
controlled release/delivery
cytotoxicity
Delayed-Action Preparations - chemistry
dispersion polymerization
drug release
Female
Humans
intracellular localization
macromonomer
MCF-7 Cells
Mice, Nude
Nanoparticles - chemistry
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - pathology
Ovary - drug effects
Ovary - pathology
Paclitaxel - administration & dosage
Paclitaxel - pharmacokinetics
Paclitaxel - pharmacology
PLA
Polyesters - chemistry
polymer synthesis
stealth nanoparticle
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Summary:The macromonomer method was used to prepare cross-linked, paclitaxel-loaded polylactide (PLA)–polyethylene glycol (stealth) nanoparticles using free-radical dispersion polymerization. The method can facilitate the attachment of other molecules to the nanoparticle surface to make it multifunctional. Proton nuclear magnetic resonance and Fourier transform infrared spectra confirm the synthesis of PLA macromonomer and cross-linking agent. The formation of stealth nanoparticles was confirmed by scanning and transmission electron microscopy. The drug release isotherm of paclitaxel-loaded nanoparticles shows that the encapsulated drug is released over 7 days. In vitro cytotoxicity assay in selected breast and ovarian cancer cell lines reveal that the blank nanoparticle is biocompatible compared with medium-only treated controls. In addition, the paclitaxel-loaded nanoparticles exhibit similar cytotoxicity compared with paclitaxel in solution. Confocal microscopy reveals that the nanoparticles are internalized by MCF-7 breast cancer cells within 1h. Preliminary biodistribution studies also show nanoparticle accumulation in tumor xenograft model. The nanoparticles are suitable for the controlled delivery of bioactive agents. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2546–2555, 2014
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.24061