Synthesis, characterisation, and in vitro cellular uptake kinetics of nanoprecipitated poly(2-methacryloyloxyethyl phosphorylcholine)-b-poly(2-(diisopropylamino)ethyl methacrylate) (MPC-DPA) polymeric nanoparticle micelles for nanomedicine applications

Jonathan Salvage, Tia Smith, Tao Lu, Amendeep Sanghera, Guy Standen, Yiqing Tang, Andrew Lewis

Research output: Contribution to journalArticle

Abstract

Nanoscience offers the potential for great advances in medical technology and therapies in the form of nanomedicine. As such, developing controllable, predictable, and effective, nanoparticle-based therapeutic systems remains a significant challenge. Many polymer-based nanoparticle systems have been reported to date, but few harness materials with accepted biocompatibility. Phosphorylcholine (PC) based biomimetic materials have a long history of successful translation into effective commercial medical technologies. This study investigated the synthesis, characterisation, nanoprecipitation, and in vitro cellular uptake kinetics of PC-based polymeric nanoparticle micelles (PNM) formed by the biocompatible and pH responsive block copolymer poly(2-methacryloyloxyethyl phosphorylcholine)- b-poly(2-(diisopropylamino)ethyl methacrylate) (MPC-DPA). Atom transfer radical polymerisation (ATRP), and gel permeation chromatography (GPC) were used to synthesise and characterise the well-defined MPC100-DPA100 polymer, revealing organic GPC, using evaporative light scatter detection, to be more accurate than aqueous GPC for this application. Subsequent nanoprecipitation investigations utilising photon correlation spectroscopy (PCS) revealed PNM size increased with polymer concentration, and conferred Cryo-stability. PNM diameters ranged from circa 64–69nm, and increased upon hydrophobic compound loading, circa 65–71nm, with loading efficiencies of circa 60% achieved, whilst remaining monodisperse. In vitro studies demonstrated that the PNM were of low cellular toxicity, with colony formation and MTT assays, utilising V79 and 3T3 cells, yielding comparable results. Investigation of the in vitro cellular uptake kinetics revealed rapid, 1h, cellular uptake of MPC100-DPA100 PNM delivered fluorescent probes, with fluorescence persistence for 48h. This paper presents the first report of these novel findings, which highlight the potential of the system for nanomedicine application development.
Original languageEnglish
Pages (from-to)1073-1094
Number of pages22
JournalApplied Nanoscience
Volume6
Issue number7
DOIs
Publication statusPublished - 23 Jan 2016

Bibliographical note

© The Author(s) 2016. This article is published with open access at Springerlink.com

Keywords

  • Nanomedicine
  • Phosphorylcholine
  • MPC-DPA
  • Micelle
  • Nanoparticle
  • Drug delivery

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