Effect of chitosan on the release of protein from thermosensitive poly(organophosphazene) hydrogels.
Poly(organophosphazenes) have been suggested as a potential thermosensitive hydrogel for use in the development of an injectable gel-depot system. Under biological conditions, hydrophilic model protein drugs, including bovine serum albumin (BSA), gelatin type B (MW 20,000) (GB20), and fluorescein isothiocyanate albumin (FITC-albumin) loaded in the hydrogels were released for 1-2 weeks, showing an initial burst release. However, this initial burst release could be suppressed when the proteins were couched in a complex with chitosan, and under these conditions evidenced a prolonged release period. BSA, GB20, and FITC-albumin, all of which are negatively charged at a pH of 7.4, interacted with chitosan harboring positive amine groups. The formation of these protein/chitosan complexes were confirmed via measurements of changes in zeta-potential and high-performance liquid chromatography. We determined the appropriate ratio of proteins to chitosan for suppression of the initial burst to be 1:5 to 1:10. From these findings, we were able to conclude that both the release rate and release period could be controlled via the formation of protein/chitosan complex.
Kang
Gyung Don
GD
Division of Life Science, Korea Institute of Science and Technology, Seoul 130-650, Republic of Korea.
Song
Soo-Chang
SC
D048271:Chitosan / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006358:Hot Temperature; D020100:Hydrogels; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D009943:Organophosphorus Compounds / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*
D005456:Fluorescent Dyes; D020100:Hydrogels; D009943:Organophosphorus Compounds; D011108:Polymers; D011506:Proteins; C515246:poly(organophosphazene); D048271:Chitosan; D016650:Fluorescein-5-isothiocyanate