Synthesis and properties of charge-shifting polycations: poly[3-aminopropyl methacrylamide-co-N,N-dimethylaminoethyl acrylate]
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1
McMaster University, Chemistry and Chemical Biology, Canada
Introduction: Polyelectrolytes have been used extensively in biomaterials as the electrostatic interaction of oppositely charged polymers allow for their self-assembly into various polyelectrolyte complexes. However, high charge density polyelectrolytes, in particular polycations, can show poor biocompatibility due to protein binding and cytotoxicity. We are interested in using synthetic polyelectrolytes for the encapsulation and immuno-isolation of mammalian cells as an approach to cell-based therapies for enzyme and hormone deficiency disorders. The standard APA capsule, composed of calcium alginate cores coated with poly(L-lysine) (PLL) and a final alginate layer, have shown issues with mechanical stability and biocompatibility. In this work, a novel copolymer of N,N-dimethylaminoethyl acrylate (DMAEA) and N-(3-aminopropyl)methacrylamide (APM) was studied as a potential replacement for high charge density polycations such as PLL. Highly cationic p(APM-co-DMAEA) (PAD) copolymers have the ability to a) form strong polyelectrolyte complexes with polyanions such as alginate, b) be covalently crosslinked, and finally c) undergo hydrolysis of DMAEA units to reduce or even invert the cationic charge density, thereby increasing the cyto- and host-compatibility of the resulting polymer network.
Materials and Methods: PAD copolymers with targeted compositions of 25, 50, and 75 mol% DMAEA of approximately 8 and 30 kDa were synthesized by Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerization. Charge-shifting hydrolysis of PAD copolymers in solution was studied by 1H NMR to probe the effects of composition and pH. PAD was coated onto anionic particles and the resulting capsule hydrogel network was characterized by confocal laser scanning microscopy (CLSM) and electrophoretic mobility measurements to monitor the effects of charge-shifting. The capsule membrane was cross-linked by reaction of the primary amine of APM units and small-molecule cross-linker tetrakis(hydroxymethyl)phosphonium chloride (THPC) to form a covalent network.
Results and Discussion: In contrast to recent reports in the literature, the rate of hydrolysis of polymeric DMAEA was found to be pH dependent (pH 9 > 7 > 5). PAD copolymers with high initial cationic charge density bound strongly to anionic surfaces forming capsule membrane structures with varying thicknesses corresponding to molecular weight. PAD-coated surfaces were covalently cross-linked via the APM units with THPC forming amine cross-linkages. The cross-linked capsules remained intact after charge-shifting hydrolysis, as well as treatments to high pH and ionic strengths. Electrophoretic mobility measurements of PAD coated particles show a positive initial mobility, then a decrease and subsequent inversion of electrophoretic mobility after hydrolysis of DMAEA.
Conclusion: PAD copolymers show promise as charge-shifting polycations for applications requiring strong interactions with anionic surfaces, the capability of covalent crosslinking, and the potential to shift and invert charge.
Natural Sciences and Engineering Research Council of Canada (NSERC) - CREATE Program and Discovery Grant
Keywords:
Hydrogel,
biomaterial,
Capsule,
Polymeric material
Conference:
10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.
Presentation Type:
Poster
Topic:
Biomaterials for therapeutic delivery
Citation:
Ros
S,
Burke
NA and
Stover
HD
(2016). Synthesis and properties of charge-shifting polycations: poly[3-aminopropyl methacrylamide-co-N,N-dimethylaminoethyl acrylate].
Front. Bioeng. Biotechnol.
Conference Abstract:
10th World Biomaterials Congress.
doi: 10.3389/conf.FBIOE.2016.01.01673
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Received:
27 Mar 2016;
Published Online:
30 Mar 2016.
*
Correspondence:
Dr. Samantha Ros, McMaster University, Chemistry and Chemical Biology, Hamilton, ON, Canada, Email1
Dr. Nicholas A Burke, McMaster University, Chemistry and Chemical Biology, Hamilton, ON, Canada, burken@mcmaster.ca
Dr. Harald D Stover, McMaster University, Chemistry and Chemical Biology, Hamilton, ON, Canada, stoverh@mcmaster.ca