Dynamic Intracellular Delivery of Antibiotics Via PH-Responsive Polymersomes
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. 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.
D. D. Lane et al., "Dynamic Intracellular Delivery of Antibiotics Via PH-Responsive Polymersomes," Polymer Chemistry, vol. 6, no. 8, pp. 1255 - 1266, Royal Society of Chemistry, Feb 2015.
The definitive version is available at https://doi.org/10.1039/c4py01249f
Materials Science and Engineering
Keywords and Phrases
Antibiotics; Blood; Chains; Dynamic light scattering; Free radical polymerization; Grafting (chemical); Light scattering; Molecular weight; Molecular weight distribution; Monomers; Polyethylene glycols; Polymerization; Scaffolds (biology), 2-hydroxyethyl methacrylate; Degrees of polymerizations; Dimethylaminoethyl methacrylates; Drug release properties; Narrow molecular weight distributions; Poly(ethylene glycol) methyl ether methacrylate (PEG-MMA); Red blood cell hemolysis; Reversible addition-fragmentation chain transfer polymerization, Polymers
International Standard Serial Number (ISSN)
Article - Journal
© 2015 Royal Society of Chemistry, All rights reserved.
01 Feb 2015