Abstract B90: Poly (lactide)-based nanoparticles by free-radical dispersion polymerization: Fabrication, characterization and in vitro studies

Abstract

Abstract We have used the macromonomer method to prepare crosslinked, paclitaxel-loaded PLA-PEG (stealth) nanoparticles using free-radical dispersion polymerization. The nanoparticles were optimized using statistical D-optimal mixture design. Nanoparticle fabrication with poly(lactide) is mainly carried out by the dispersion of preformed polymers which makes it difficult to attach targeting moieties to the surface of the nanoparticle and to produce crosslinked networks; hence we designed a new approach based on dispersion polymerization. Confirmation of nanoparticle synthesis was by scanning electron microscopy. Particle size and size distribution and the zeta potential of the optimized formulation were determined using Zetasizer nano Zs. The release profile of paclitaxel-loaded nanoparticles was determined by high performance liquid chromatography and encapsulated drug was released over 7 days. In vitro cytotoxicity studies were carried out using the CellTiter®glo luminescent cell viability assay in MCF7, MDA-MB-231 (breast cancer) and SK-OV-3 (ovarian cancer) cell lines. The cytotoxicity assay shows that the blank nanoparticle is biocompatible with no toxicity for the duration of the assay compared to medium-only treated controls. Further, the paclitaxel-loaded nanoparticle formulation exhibits similar cytotoxicity compared to free drug in solution against the cancer cell lines tested. In vitro intracellular localization of nanoparticle by confocal microscopy also demonstrated that the nanoparticles are rapidly internalized by MCF-7 cancer cells within one hour probably by nonspecific endocytosis. The stealth nanoparticles are suitable for the design of controlled delivery systems for bioactive agents. Citation Format: Simeon K. Adesina, Emmanuel O. Akala. Poly (lactide)-based nanoparticles by free-radical dispersion polymerization: Fabrication, characterization and in vitro studies. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B90.