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

• Published in: Applied nanoscience Vol. 6; no. 7; pp. 1073 - 1094
• Main Authors: Salvage, Jonathan P, Smith, Tia, Lu, Tao, Sanghera, Amendeep, Standen, Guy, Tang, Yiqing, Lewis, Andrew L
• Format: Journal Article
• Language: English
• Published: 01.10.2016
• Subjects: Biocompatibility; Evaporative; Fluorescence; In vitro testing; Micelles; Nanostructure; Synthesis; Uptakes
• ISSN: 2190-5509; 2190-5517
• DOI: 10.1007/s13204-016-0520-4

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)ethy l methacrylate) (MPC-DPA). Atom transfer radical polymerisation (ATRP), and gel permeation chromatography (GPC) were used to synthesise and characterise the well-defined MPC sub(100)-DPA sub(100) 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 64-69 nm, and increased upon hydrophobic compound loading, circa 65-71 nm, 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, 1 h, cellular uptake of MPC sub(100)-DPA sub(100) PNM delivered fluorescent probes, with fluorescence persistence for 48 h. This paper presents the first report of these novel findings, which highlight the potential of the system for nanomedicine application development.