title: Novel biocompatible phosphorylcholine-based self-assembled nanoparticles for drug delivery.
abstract: 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.
authors.affiliation: Biomedical Materials Research Group, School of Pharmacy and Biomolecular Sciences, University of Brighton, Moulsecoomb, Brighton BN2 4GJ, UK.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Salvage
authors.forename: Susanna F
authors.initials: SF
authors.lastname: Rose
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Phillips
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Hanlon
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Lloyd
authors.forename: Iris Y
authors.initials: IY
authors.lastname: Ma
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Armes
authors.forename: Norman C
authors.initials: NC
authors.lastname: Billingham
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lewis
mesh_terms: D001672:Biocompatible Materials / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D008689:Methacrylates / Q000008:administration & dosage*; D008823:Micelles; D049329:Nanostructures; D010316:Particle Size; D010767:Phosphorylcholine / Q000008:administration & dosage*
chemical_list: D001672:Biocompatible Materials; D008689:Methacrylates; D008823:Micelles; D010767:Phosphorylcholine