Paper of the week: Dynamic intracellular delivery of antibiotics via pH-responsive polymersomes

Lane et al. report the intracellular delivery of antibiotics via pH-responsive polymersomes.

Reversible addition-fragmentation chain transfer (RAFT) polymerisation was employed to prepare a series of copolymers consisting of 2-hydroxyethyl methacrylate (HEMA) and poly(ethylene glycol) methyl ether methacrylate (FWavg [similar] 950 Da) (O950) with variable comonomer compositions and molecular weights for use as polymeric scaffolds. Reactivity ratios for the monomer pair were determined to be 1.37 and 0.290 respectively. To these scaffolds, trithiocarbonate-based RAFT chain transfer agents (CTAs) were grafted using carbodiimide chemistry. The resultant graft chain transfer agents (gCTA) were subsequently employed to polymerise dimethylaminoethyl methacrylate (DMAEMA) and N-(2-hydroxypropyl)methacrylamide (HPMA) between degrees of polymerisation (DP) of 25 and 200. Kinetic analysis for the polymerisation of DMAEMA targeting a DP of 100 from a 34 arm graft gCTA show linear Mn conversion and pseudo first order rate plots with narrow molecular weight distributions that move toward lower elution volumes with monomer conversion. Đ values for these polymerisations remain low at around 1.20 at monomer conversions as high as 70%. pH-responsive endosomalytic brushes capable of spontaneously self-assembling into polymersomes were synthesised and a combination of dynamic light scattering (DLS), cryoTEM, and red blood cell haemolysis were employed to evaluate the aqueous solution properties of the polymeric brush as a function of pH. Successful encapsulation of ceftazidime and pH-dependent drug release properties were confirmed by HPLC. Intracellular antibiotic activity of the drug-loaded polymersomes was confirmed in a macrophage coculture model of infection with Burkholderia thailandensis and RAW 264.7 cells.

Dynamic intracellular delivery of antibiotics via pH-responsive polymersomes by D. D. Lane, F. Y. Su, D. Y. Chiu, S. Srinivasan, J. T. Wilson, D. M. Ratner, P. S. Stayton and A. J. Convertine, Polym. Chem., 2015,6, 1255-1266.

Remzi Becer is a web-writer and Advisory Board member for Polymer Chemistry. He is currently a Senior Lecturer in Materials Science and the director of the Polymer Science and Nanotechnology masters programme at Queen Mary, University of London. Visit www.becergroup.com for more information.

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