Water-soluble and nonionic polyphosphoester: synthesis, degradation, biocompatibility and enhancement of gene expression in mouse muscle.
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.
Tissue & Therapeutic Engineering Lab, Johns Hopkins Singapore, Singapore 117597.
Shi-Wen
SW
Huang
Jun
J
Wang
Peng-Chi
PC
Zhang
Hai-Quan
HQ
Mao
Ren-Xi
RX
Zhuo
Kam W
KW
Leong
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry / Q000494:pharmacology*; D011122:Polyphosphates / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility / Q000187:drug effects; D014867:Water
D001672:Biocompatible Materials; D011091:Polyesters; D011122:Polyphosphates; D014867:Water