Soluble curcumin amalgamated chitosan microspheres augmented drug delivery and cytotoxicity in colon cancer cells: In vitro and in vivo study

In present investigation, initially curcumin was complexed with 2-HP-beta-CD (curcumin-2-HP-beta-CD-complex) in 1:1 ratio and later amalgamated with chitosan microspheres (curcumin-2-HP-(3-CD-CMs) for selective delivery in colon only through oral route of administration. Various analytical, spectral and in-silico docking techniques revealed that the curcumin was deeply inserted in the 2-HP-beta-CD cavity with apparent stability constant of 3.35 x 10(-3) M. Furthermore, the mean particle size of 6.8 +/- 2.6 pm and +39.2 +/- 4.1 mV surface charge of curcumin-2-HP-beta-CD-complex-CMs in addition to encapsulation efficiency of about 79.8 +/- 6.3% exhibited that the tailored microspheres were optimum for colon delivery of curcumin. This was also demonstrated in dissolution testing and standard cell proliferation assay in which curcumin-2-HP-beta-CD-complex-CMs exhibited maximum release in simulated colonic fluid (SCF, pH similar to 7.0-8.0, almond emulsion-beta-glucosidase) with improved therapeutic index in HT-29 cells. Consistently, curcumin-2-HP-beta-CD-complex-CMs successively enhanced the colonic bio-distribution of curcumin by similar to 8.36 folds as compared to curcumin suspension in preclinical pharmacokinetic studies. In conclusion, curcumin-2-HP-beta-CD-complex-CMs warrant further in vivo tumor regression study to establish its therapeutic efficacy in experimental colon cancer. (C) 2016 Published by Elsevier B.V.