Novel formulation of solid lipid microparticles of curcumin for anti-angiogenic and anti-inflammatory activity for optimization of therapy of inflammatory bowel disease.
OBJECTIVE
This project was undertaken with a view to optimize the treatment of inflammatory bowel disease through a novel drug delivery approach for localized treatment in the colon. Curcumin has poor aqueous solubility, poor stability in the gastrointestinal tract and poor bioavailability. The purpose of the study was to prepare and evaluate the anti-inflammatory activity of solid lipid microparticles (SLMs) of curcumin for the treatment of inflammatory bowel disease in a colitis-induced rat model by a colon-specific delivery approach.


METHODS
We have developed a novel formulation approach for treating experimental colitis in the rat model. SLMs of curcumin were prepared with various lipids, such as palmitic acid, stearic acid and soya lecithin, with an optimized percentage of poloxamer 188. The SLMs of curcumin were characterized for particle size, drug content, drug entrapment, in-vitro release, surface morphology and infrared, differential scanning calorimetry and X-ray studies. The colonic delivery system of SLM formulations of curcumin were further investigated for their anti-angiogenic and anti-inflammatory activity using chick embryo and rat colitis models.


RESULTS
Particle size, drug content, drug entrapment and in-vitro release studies showed that formulation F4 containing one part stearic acid and 0.5% surfactant had the smallest diameter of 108 microm, 79.24% entrapment and exhibited excellent in-vitro release characteristics when compared with other formulations and pure curcumin. SLMs of curcumin (F4) proved to be a potent angio-inhibitory compound, as demonstrated by inhibition of angiogenesis in the chorioallantoic membrane assay. Rats treated with curcumin and its SLM complex showed a faster weight gain compared with dextran sulfate solution (DSS) control rats. The increase in whole colon length appeared to be significantly greater in SLM-treated rats when compared with pure curcumin and DSS control rats. An additional finding in the DSS-treated rats was chronic cell infiltration with predominance of eosinophils. Decreased mast cell numbers in the mucosa of the colon of SLMs of curcumin and pure curcumin-treated rats was observed.


CONCLUSIONS
The degree of colitis caused by administration of DSS was significantly attenuated by colonic delivery of SLMs of curcumin. Being a nontoxic natural dietary product, curcumin could be useful in the therapeutic strategy for inflammatory bowel disease patients.
Yadav
Vivek Ramshankar
VR
SRF, Department of Pharmaceutics, India.
Suresh
Sarasija
S
Devi
Kshama
K
Yadav
Seema
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002642:Chick Embryo; D049033:Chorioallantoic Membrane; D003092:Colitis / Q000188:drug therapy* / Q000503:physiopathology; D003474:Curcumin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D054709:Lecithins / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008297:Male; D008863:Microspheres; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D019308:Palmitic Acid / Q000737:chemistry; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013025:Glycine max / Q000737:chemistry; D013229:Stearic Acids / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D054709:Lecithins; D008055:Lipids; D013229:Stearic Acids; D019308:Palmitic Acid; C031183:stearic acid; D003474:Curcumin