Studies On Chitosan Microparticles Drug Delivery System Of Curcumin

Curcumin, a polyphenolic compound derived from dietary spice turmeric,possesses diverse pharmacologic effects including anti-infammatory, antioxidant,antiproliferative and antiangiogenic activities. However, its limited aqueous solubilityand degradation at alkaline pH restricts its bioavailability. Phase I clinical trials haveshown that curcumin is safe even at high doses (12g/day) in humans but exhibitpoor bioavailability. Major reasons contributing to the low plasma and tissue levels ofcurcumin appear to be due to poor absorption, rapid metabolism and systemicelimination. To improve dissolution and bioavailability of this poorly water-solubledrug, curcumin loaded chitosan microparticles (Cs-MPs-Cur) were prepared withsodium tripolyphosphate (TPP) by ionotropic gelation method.Analytical methods of curcumin were established in vitro and in vivo. UVspectrophotometry was developed for assay of drug release of curcumin inCs-MPs-Cur in vitro. High-performance liquid chromatography was applied indetermination of stability of curcumin, content of curcumin in Cs-MPs-Curpreparations and plasma concentration. The methods with high sensitivity andspecificity were suitable for the regulations of Pharmacopoeia of People’s Republic ofChina.Response surface methodology (RSM) based on a three-factor, three-levelBox-Behnken Design (BBD) was used to optimize the conditions of Cs-MPs-Cur forthe sustained release of curcumin. The three independent variables (concentration ofacetic acid, ratio of chitosan to curcumin and concentration of TPP) were studied onfive responses: the loading capacity, entrapment efficiency, yield, cumulative releaseand burst release. The optimal conditions were found to be:1%(v/v) of acetic acidconcentration,0.8(w/w) of Cs/Cur ratio,0.15%(w/v) of TPP concentration. Loadingcapacity, encapsulation efficiency and yield of the optimized Cs-MPs-Cur were62.92%,95.41%and66.20%, respectively with83.60%cumulative release and18.45%burst release. Good correspondence between calculated and experimentalvalues indicated validityof the generated statistical models for the responses.Scanning electron microscopy (SEM) provided better understanding of themorphological characteristics of Cs-MPs-Cur, which had a smooth surface and spherical shape. The particle size and distribution of Cs-MPs-Cur were measured witha laser diffraction particle size analyzer. About50%of the measured particles werefound to have a mean particle size of10.68μm. X-Ray diffraction (XRD) wasperformed to elucidate the physical structure of the drug in Cs-MPs-Cur. The resultindicated that some amount of the drug was still present in crystalline form thoughobvious diffraction peaks of Cur were reduced apparently in XRD pattern ofCs-MPs-Cur. The FT-IR spectra corresponding to Cs-MPs-Cur displayed all thecharacteristic bands of both Cur and Cs without any spectral shifts in either bandwhich indicated that there was no chemical interaction between the components ofCs-MPs-Cur.The stability tests proved the acceptable stability of the optimal formulation ofCs-MPs-Cur.The pharmacokinetic investigations ofCs-MPs-Cur were performed on rats. Peakplasma concentration (Cmax) of Cs-MPs-Cur were increased9times and the areaunder the curve from0to t (AUC0-t) were increased nearly15times compared to thecurcumin.In conclusion, our studies proved that Cs-MPs-Cur were promising andconvenient methods for improving oral absorption of Cur with poor aqueoussolubility and short biologic half-life.