This research studied modification of gelatin, a soluble protein wildly used in pharmaceutical applications, by conjugating with 25 -125% (mole) cholesterol using N,N'- disuccinimidyl carbonate as a conjugating agent. The success of structural modification was evaluated from the 13-40% reduction of free –NH₂ groups in gelatin, increasing hydrophobicities of the modified gelatin films and structural changes examined by FT-IR. Modified gelatin was fabricated into hydrogel patches and was chemical crosslinked with glutaraldehyde. Water swelling, enzymatic degradation, and rate of curcumin releases in vitro increased according to the amounts of cholesterol used in the modification. The modified gelatin was non-toxic to L929 mouse fibroblast cells compared to the native gelatin. Model drug used in this delivery system is curcumin (MW 368), a hydrophobic herbal extract reported to have anti-cancer effect via the inhibition of neovascularization in solid tumors. In vivo releases were tested using curcumin loaded modified gelatin patches subcutaneously implanted on the backs of nude mice (BALBc, male, 6-8 weeks). The results of high performance liquid chromatography analysis of plasma curcumin level revealed that the system could sustain the curcumin releases for at least 14 days, with the maximum peak at day 6 after implantation. Effectiveness of curcumin released of the modified gelatin patches was tested in nude mice baring HepG-2 solid tumors. The system inhibited approximately 47% neovascularization and reduced the tumor sizes by 73.18%. This work was the first reports showing development of curcumin controlled release system with the safety and efficacy tests in animals. The results indicated that this sustained release system enhances curcumin effectiveness and uses 80X lower dose compared to the treatment by mount feedings.
SUBJECT
เจลาติน
ระบบนำส่งยา
Gelatin
Drug delivery systems
LOCATION
CALL#
STATUS
Thailand and ASEAN Information Center (6th Floor) : Chula Collection
