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Issue 8, 2015
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Dynamic intracellular delivery of antibiotics via pH-responsive polymersomes

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Abstract

Reversible addition-fragmentation chain transfer (RAFT) polymerization was employed to prepare a series of copolymers consisting of 2-hydroxyethyl methacrylate (HEMA) and poly(ethylene glycol) methyl ether methacrylate (FWavg ∼ 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 polymerize dimethylaminoethyl methacrylate (DMAEMA) and (HPMA) between degrees of polymerization (DP) of 25 and 200. Kinetic analysis for the polymerization 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 polymerizations 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 synthesized and a combination of dynamic light scattering (DLS), cryoTEM, and red blood cell hemolysis 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 B. thailandensis and RAW 264.7 cells.

Graphical abstract: Dynamic intracellular delivery of antibiotics via pH-responsive polymersomes

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Publication details

The article was received on 09 Sep 2014, accepted on 18 Nov 2014 and first published on 19 Nov 2014


Article type: Paper
DOI: 10.1039/C4PY01249F
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Polym. Chem., 2015,6, 1255-1266

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    Dynamic intracellular delivery of antibiotics via pH-responsive polymersomes

    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
    DOI: 10.1039/C4PY01249F

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