Synthesis and characterization of biodegradable thermosensitive neutral and acidic poly(organophosphazene) gels bearing carboxylic acid group
The needs to develop thermosensitive biodegradable polymers have been raised in the area of injectable polymer therapeutics. The aims of this work are to develop thermosensitive biodegradable poly(organophosphazene) gels having functional group and characterize their physicochemical properties such as thermosensitivity and hydrolytic behaviors. Controlled thermosensitivity and hydrolytic degradability of polymer gels were obtained with randomly grafted amphiphilic poly(organophosphazenes). Hydrophobic L-isoleucine ethyl ester (IleOEt) and hydrophilic poly(ethylene glycol) 550 or 750 Da (PEG 550 or 750) were substituted along with relatively small amount of glycylglycine allyl ester (GlyGlyOALL) which was deprotected into glycylglycine (GlyGlyOH). By this procedure several neutral (GlyGlyOALL) and acidic (GlyGlyOH) poly(organophosphazene) pairs with same substituent ratio were prepared, in which the ratio of substituent groups could systematically modulate their thermosensitive properties. The aqueous solutions and gels of prepared acidic poly(organophosphazene) also showed the thermosensitive sol-gel transition and biodegradation at body temperature, respectively. Acidic poly(organophosphazene) exhibited much faster hydrolytic degradation than neutral polymer in the buffer solutions (pH 7.4) at 37 °C. With systematically regulated thermo-responsiveness and hydrolytic degradability, the synthesized poly(organophosphazenes) are expected to be smart injectable materials having a useful moiety and further chemically conjugated with various bioactive molecules for biomedical applications.
KeywordsInjectable Functionalization of polymer Biodegradable hydrogel Phase behavior Poly(organophosphazene) Stimuli-sensitive polymer
This research was financially supported by the Ministry of Education, Science and Technology in Korea. The authors would like to thank Dr. ChangJu Chun for his kind advices and scientific discussion.
- 9.Rathi RC, Zentner GM and Jeong B (2001) Biodegradable low molecular weight triblock poly(lactide-co- glycolide) polyethylene glycol copolymers having reverse thermal gelation properties US Patent 6201072Google Scholar
- 11.Aoyagi TE, Mitsuhiro; Sakai, Kiyotaka; Sakurai, Yasuhisa; Okano, Teruo (2000) J Biomater Sci Polym Ed 11:10Google Scholar
- 29.Andrianov AK, Payne LG (1996) Polyphosphazene Hydrogel Microspheres for Protein Delivery. In: Smadar Cohen HB (ed) Microparticulate Systems for the Delivery of Proteins and Vaccines (Drugs and the Pharmaceutical Sciences), 1st edn. Marcel Dekker, New YorkGoogle Scholar
- 32.Allcock HR (2003) Chemistry and applications of polyphosphazenes. John Wiley & Sons, New JerseyGoogle Scholar
- 38.Greenstein JP, Winitz M (1961) Chemistry of the Amino Acids. John Wiley & Son, New YorkGoogle Scholar
- 45.Evans DF and Wennerström H (1999) The Colloidal Domain: Where Physics, Chemistry, Biology, and Technology Meet Wiley-VCH, New York.Google Scholar
- 47.Harris JM (1992) Introduction to Biotechnical and Biomedical Applications of Poly(Ethylene Glycol). In: Harris JM (ed) Poly(Ethylene Glycol) Chemistry: Biotechnical and Biomedical Applications (Topics in Applied Chemistry), 1st edn. Plenum Press, New YorkGoogle Scholar