Novel biocompatible phosphorylcholine-based self-assembled nanoparticles for drug delivery
Salvage, J.P., Rose, S.F., Phillips, G.J., Hanlon, G.W., Lloyd, A.W., Ma, I.Y., Armes, S.P., Billingham, N.C. and Lewis, A.L. (2005) Novel biocompatible phosphorylcholine-based self-assembled nanoparticles for drug delivery Journal of controlled release, 104 (2). pp. 259-270. ISSN 0168-3659
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Official URL: http://dx.doi.org/10.1016/j.jconrel.2005.02.003
Major challenges associated with nano-sized drug delivery systems include removal from systemic circulation by phagocytic cells and controlling appropriate drug release at target sites. 2-methacryloyloxyethyl phosphorylcholine (MPC) has been copolymerised in turn with two pH responsive comonomers (2-(diethylamino)ethyl methacrylate (DEA) and 2-(diisopropylamino)ethyl methacrylate (DPA), to develop novel biocompatible drug delivery vehicles. Micelles were prepared from a series of copolymers with varying block compositions and their colloidal stability and dimensions were assessed over a range of solution pH using photon correlation spectroscopy. The drug loading capacities of these micelles were evaluated using Orange OT dye as a model compound. The cytotoxicity of the micelles was assessed using an in vitro assay. The MPC-DEA diblock copolymers formed micelles at around pH 8 and longer DEA block lengths allowed higher drug loadings. However, these micelles were not stable at physiological pH. In contrast, MPC-DPA diblock copolymers formed micelles of circa 30 nm diameter at physiological pH. In vitro assays indicated that these MPC-DPA diblock copolymers had negligible cytotoxicities. Thus novel non-toxic biocompatible micelles of appropriate size and good colloidal stability with pH-modulated drug uptake and release can be readily produced using MPC-DPA diblock copolymers.
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