Abstract:

Polydichlophosphazene(PDCP) was prepared by the ring-opening polymerization of hexachlorocyclotriphosphazene in the presence of 2%AlCl₃. A new mixed substituent poly(organophosphazene) bearing 2-(2-oxy-1-pyrrolidiny) ethoxy and methoxyethoxyethoxy side groups was synthesized via the macromolecular substitution reactions of poly(dichlorophosphazene) with the sodium salt of 1-(2-hydroxyethyl)-2-pyrrolidone and sodium methoxyethoxyethoxide. Its structure was verified by ³¹P NMR, ¹H NMR, ¹³C NMR, IR and DSC. Its molecular weight was determined by vapor pressure osmometry(VPO). 18-Crown-6 was used in the synthesis of poly[di(2-oxy-1-pyrrolidiny)ethoxyphophazene](PYRP) as phase transfer catalysis in order to improve its synthetic method. The new polymer and PYRP were water-soluble and their in vitro degradation behavior was studied at varied pH conditions. The results indicate that the degradation of poly(organophosphazenes) with (2-oxy-1-pyrrolidiny)ethoxy side groups is dependent on pH of the buffer solution. The rate of hydrolysis was more rapid at pH=5.0 than at pH=7.4 and pH=8.0. It was shown that addition of methoxyethoxyethoxy side group to PYRP structure resulted in a decrease in the rate of hydrolysis. The hydrolysis products of the poly(organophosphazenes) were analyzed by ³¹P NMR, thin layer chromatography(TLC) and titration methods. A hydrolysis pathway of the new polymer in buffer solutions with pH=5.0, 7.4 and 8.0 was proposed. The degradation of the polymers at pH=5.0 involved a hydrolytic cleavage of (2-oxy-1-pyrrolidiny)ethoxy from the chain followed by the degradation of the phosphorus-nitrogen backbone to form phosphate and ammonium. However, the degradation of the polymers at pH=7.4 and pH=8.0 was only cleavage of the side group. The MTT test for the new polymer and its hydrolysis products at pH=5.0 in HepG2 cell revealed that an increase in polymer concentration from 1.3 to 800 μg/mL was not harmful for the cell survival. The hydrolysis products of the new polymer at 800 μg/mL were able to promote cell proliferation.

Key words: Polyphosphazene, 2-(2-Oxy-1-pyrrolidiny)ethoxy, Methoxyethoxyethoxy, pH-sensitive hydrolytic degradation property, Hydrolysis pathway, In vitro cytotoxicity