Abstract
A nonionic and water-soluble polyphosphoester, poly(2-hydroxyethyl propylene phosphate) (PPE3), was synthesized by chlorination of poly(4-methyl-2-oxo-2-hydro-1,3,2-dioxaphospholane), followed by esterification with 2-benzyloxyethanol and deprotection of the hydroxyl group by catalytic hydrogenation in the presence of Pd-C. PPE3 degraded rapidly in PBS 7.4 at 37 degrees C. The cytotoxicity and tissue compatibility assays suggested good biocompatibility of PPE3 in vitro and in vivo. The expression of pVR1255 Luc plasmid in mouse muscle after intramuscular (i.m.) injection of DNA formulated with PPE3 solution in saline was enhanced up to 4-fold compared with that of naked DNA. These results suggest the potential of this polyphosphoester for naked DNA-based gene therapy. The advantages of this polymer design include the biodegradability of the polyphosphoester and its structural versatility, which allows the fine-tuning of the physicochemical properties to optimize the enhancement of gene expression in muscle.
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