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

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

Nanostructured DPA-MPC-DPA triblock copolymer gel for controlled drug release of ketoprofen and spironolactone

“…One strategy to achieve this is to mimic cell membrane components, and thus, copolymers utilising phosphorylcholine (PC) have been developed for biomedical applications, including those that form hydrogels . An example of PC‐containing polymers are the poly(2‐methacryloyloxyethyl phosphorylcholine)‐ b ‐poly(2‐(diisopropylamino)ethyl methacrylate) (MPC‐DPA) range of diblock copolymers that have been developed for nanoparticle suspension drug delivery applications . The MPC component is biocompatible and able to resist protein adsorption and cell adhesion, due to high levels of water binding; however, the MPC‐DPA diblock copolymers do not form gels .…”

Interactions of environmental and therapeutic particles with the airway microenvironment

“…Chemical shifts were matched to previously reported NMR spectra of pMPC-containing polymers to confirm polymer chemistry. 95,[227][228][229] Conversion was qualitatively confirmed with NMR by monitoring the disappearance of the two peaks at 5. When pMPC coatings were formed onto gold nanoparticles at high polymer:gold mass ratios (30:1), TEM imaging captured particles that were agglomerated, and associated with polymer globs that appear as shaded regions ( Figure 6.7b).…”

“…Peaks were matched to literature values for monomer and polymer to confirm chemistry. 95,[227][228][229] Conversion was qualitatively confirmed by monitoring the reduction of two alkene peaks at 5.6 and 6.1 ppm.…”

“…In the case of drug delivery, most systems using phosphorylcholine involve the incorporation of pMPC into copolymers for the formation of polymersomes to encapsulate and deliver drugs. 95,96 Copolymers containing pMPC have been developed as coatings onto gold surfaces. These systems have been designed to coat gold using initiator chemistry to generate thiol end-functionality 69 or using the pMPC-containing copolymer as the reducing agent to facilitate gold nanoparticle formation by reduction of tetrachloroauric acid 208 .…”

“…94 In the case of drug delivery, some have demonstrated synthesis of pMPC copolymers for the formation of polymersomes to encapsulate and deliver drugs. 95,96 A carboxybetaine methacrylate has been demonstrated to stabilize liposomes to increase circulation time. 97 Beyond their potential use in particles for drug delivery, carboxybetaine and sulfobetaine functionalized polymers are being used to design materials for implants.…”