Novel biocompatible phosphorylcholine-based self-assembled nanoparticles for drug delivery

Jonathan Salvage, S.F. Rose, Gary Phillips, Geoff Hanlon, Andrew Lloyd, I.Y. Ma, S.P. Armes, N.C. Billingham, A.L. Lewis

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)259-270
Number of pages12
JournalJournal of Controlled Release
Volume104
Issue number2
DOIs
Publication statusPublished - May 2005

Keywords

  • pH-responsive
  • Nanoparticles
  • Drug delivery
  • Phosphorylcholine
  • Block copolymers

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    Salvage, J., Rose, S. F., Phillips, G., Hanlon, G., Lloyd, A., Ma, I. Y., Armes, S. P., Billingham, N. C., & Lewis, A. L. (2005). Novel biocompatible phosphorylcholine-based self-assembled nanoparticles for drug delivery. Journal of Controlled Release, 104(2), 259-270. https://doi.org/10.1016/j.jconrel.2005.02.003