title: Polylactide-based paclitaxel-loaded nanoparticles fabricated by dispersion polymerization: characterization, evaluation in cancer cell lines, and preliminary biodistribution studies.
abstract: 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 1 h. Preliminary biodistribution studies also show nanoparticle accumulation in tumor xenograft model. The nanoparticles are suitable for the controlled delivery of bioactive agents.
authors: Department of Pharmaceutical Sciences, Howard University, Washington, D.C.
authors: Simeon K
authors: SK
authors: Adesina
authors: Alesia
authors: A
authors: Holly
authors: Gabriela
authors: G
authors: Kramer-Marek
authors: Jacek
authors: J
authors: Capala
authors: Emmanuel O
authors: EO
authors: Akala
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001940:Breast / Q000187:drug effects / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000737:chemistry*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D011091:Polyesters / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D011091:Polyesters; C033616:poly(lactide); D017239:Paclitaxel
keywords: PLA; biodegradable polymers; cell culture; controlled release/delivery; cytotoxicity; dispersion polymerization; drug release; intracellular localization; macromonomer; polymer synthesis; stealth nanoparticle