title: Biodegradable branched polycationic polymers with varying hydrophilic spacers for nonviral gene delivery.
abstract: Biodegradable branched polycationic polymers with varying hydrophilic spacer lengths were synthesized from different triacrylate monomers and the amine monomer 1-(2-aminoethyl)piperazine by Michael addition polymerization. The hydrophilic spacers were varied by the number of ethyleneoxy groups in the triacrylate monomer (E/M) that ranged from 0 to 14. The polymer degradation depended on the spacer length and pH; the amount of ester degraded as determined by (1)H NMR after 14 days was 43.4 +/- 2.1% (pH 5.0) and 89.7 +/- 1.3% (pH 7.4) for the polymer with 0 E/M compared to 55.7 +/- 2.6% (pH 5.0) and 98.5 +/- 1.6% (pH 7.4) for the polymer with 14 E/M. Cell viability of rat fibroblasts after exposure to polymer solutions of concentrations up to 1000 microg/mL remained high (above 66.9 +/- 12.1% compared to below 7.6 +/- 1.1% for polyethylenimine at a concentration of 50 microg/mL or higher) and increased with the spacer length. The polyplexes made with all the synthesized polymers showed higher transfection efficiency (4.5 +/- 1.7% to 9.4 +/- 2.0%, dependent on the polymer/pDNA weight ratio) with an enhanced green fluorescent protein reporter gene compared to naked pDNA (0.8 +/- 0.4%) as quantified by flow cytometry. This study demonstrates that hydrophilic spacers can be incorporated into polycationic polymers to reduce their cytotoxicity and enhance their degradability for nonviral gene delivery.
authors.affiliation: Department of Bioengineering, Rice University, MS-142, PO Box 1892, Houston, Texas 77251-1892, USA.
authors.forename: Sue Anne
authors.initials: SA
authors.lastname: Chew
authors.forename: Michael C
authors.initials: MC
authors.lastname: Hacker
authors.forename: Anita
authors.initials: A
authors.lastname: Saraf
authors.forename: Robert M
authors.initials: RM
authors.lastname: Raphael
authors.forename: F Kurtis
authors.initials: FK
authors.lastname: Kasper
authors.forename: Antonios G
authors.initials: AG
authors.lastname: Mikos
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology; D018014:Gene Transfer Techniques; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000071228:Polyelectrolytes; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D055672:Static Electricity
chemical_list: D011073:Polyamines; D000071228:Polyelectrolytes; D011108:Polymers
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