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 64–69 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 MPC100-DPA100 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.
Highlights
Recent estimates place the annual global incidence of, and mortality from, human cancers at circa 14 and 8 million cases per annum and growing (Torre et al 2015)
This paper reports for the first time novel data and findings regarding MPC100-DPA100 polymeric nanoparticle micelles (PNM) formation, stability, loading, and intracellular uptake kinetics, which aids to further the understanding of applied endocytosis, for these PC-based PNM systems to be harnessed for effective intracellular delivery applications, and potentially nanomedicine
Synthesis of the MPC100-DPA100 diblock copolymer was undertaken via Atom transfer radical polymerisation (ATRP), and characterised with 1H nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC)
Summary
Recent estimates place the annual global incidence of, and mortality from, human cancers at circa 14 and 8 million cases per annum and growing (Torre et al 2015). Phosphorylcholine (PC) based polymers (Hayward and Chapman 1984) have a successful record of innovative biomaterials development and application (Lewis 2000), including biocompatible pH responsive polymeric NIDS (Salvage et al 2005). As such a number of studies have explored the in vitro cellular uptake of pH responsive poly(2-methacryloyloxyethyl phosphorylcholine)-bpoly(2-(diisopropylamino)ethyl methacrylate) (MPC-DPA)
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