Core-shell microspheres with surface grafted poly(vinyl alcohol) as drug carriers for the treatment of hepatocellular carcinoma

• Published in: Journal of polymer science. Part A, Polymer chemistry Polymer chemistry, 2007-08, Vol.45 (15), p.3256-3272
• Main Authors: Nguyen, T. L. Uyen, Farrugia, Brooke, Davis, Thomas P., Barner-Kowollik, Christopher, Stenzel, Martina H.
• Format: Article
• Language: English
• Subjects: Applied sciences; Biological and medical sciences; biomaterials; core-shell microspheres; core-shell polymers; drug delivery; Exact sciences and technology; General pharmacology; hepatocellular carcinoma; Medical sciences; Organic polymers; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; poly(vinyl alcohol); Polymerization; Preparation, kinetics, thermodynamics, mechanism and catalysts; RAFT/MADIX polymerization; reversible addition fragmentation chain transfer (RAFT)
• ISSN: 0887-624X; 1099-0518
• DOI: 10.1002/pola.22074

Core(polyvinyl neodecanoate‐ethylene glycol dimethacrylate)‐shell(polyvinyl alcohol) (core (P(VND‐EGDMA))‐shell(PVA)) microspheres were developed by seeded polymerization with the use of conventional free radical and RAFT/MADIX mediated polymerization. Poly(vinyl pivalate) PVPi was grafted onto microspheres prepared via suspension polymerization of vinylneodecanoate and ethylene glycol dimethacrylate. The amount of grafted polymer was found to be independent from the technique used with conventional free radical polymerization and MADIX polymerization resulting into similar shell thicknesses. Both systems—grafting via free radical polymerization or the MADIX process—were found to follow slightly different kinetics. While the free radical polymerization resulted in a weight gain linear with the monomer consumption in solution the growth in the MADIX controlled system experienced a delay. The core‐shell microspheres were obtained by hydrolysis of the poly(vinyl pivalate) surface grafted brushes to form poly(vinyl alcohol). During hydrolysis the microspheres lost a significant amount of weight, consistent with the hydrolysis of 40–70% of all VPi units. Drug loading was found to be independent of the shell layer thickness, suggesting that the drug loading is governed by the amount of bulk material. The shell layer does not appear to represent an obstacle to the drug ingress. Cell testing using colorectal cancer cell lines HT 29 confirm the biocompatibility of the empty microspheres whereas the clofazimine loaded particles lead to 50% cell death, confirming the release of the drug. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3256–3272, 2007 Poly(vinyl alcohol) coated microspheres were obtained by surface grafting of vinylpivalate onto beads using residual double bonds. Two techniques—free radical polymerization and the macromolecular design via the interchange of xanthates (MADIX) process—were utilized and their outcome was compared. The resulting core‐shell beads with particle sizes of around 40 μm were hydrolyzed. As a result, the microspheres were suspendable in aqueous conditions. After drug loading with clofazimine the particles were tested towards their suitability as a drug carrier system.