SYNTHESIS, SCREENING AND NANOTECHNOLOGY BASED IN VIVO DRUG DELIVERYOF CURCUMIN AND ITS ANALOGUES

Curcumin (diferuloyl methane; 1, 7-bis-(4-hydroxy-3-methoxyphenyl)-hepta-1, 6-diene-3, 5-dione) is s a natural yellow orange dye derived from the rhizome of Curcuma longa Linn. It possesses divergent pharmacological activities like anti inflammatory, antioxidant, anticancer, anti HIV, hepatoprotective, and anti diabetic activities etc.Curcumin structural analogues were synthesized and reported to possess same or superior activity compared to the curcumin. Analogues were synthesized using different aromatic substituted aldehydes and they were characterized using spectral data (FTIR, NMR). These compounds were previously screened for hepatoprotective activity. Several of them demonstrated hepatoprotective activity. In this study all the synthesised compounds were screened for anti diabetic activity. From all the six compounds synthesized,compound IIand compound IIIshowed highly significant activity than curcumin and are comparable to standard drug glibenclamide. From the six compounds synthesized, four compounds I, II, III, and VI showed superior in antidiabetic activity compared to curcumin and other two compounds IV and V are inferior in antidiabetic activity compared to curcumin. Compound II was equal in activity compared to the standard drug glibenclamide. We developed nanoparticulate and liposomal delivery systems by encapsulating the curcumin. Curcumin nanoparticles were prepared by double emulsion (w/o/w) solvent evaporation method using poly-ecaprolactone as the biodegradable polymer. Four different formulations (CNP1, CNP2, CNP3 and CNP4) were prepared by taking different drug to polymer ratios. Curcumin liposomes were prepared by thin film hydration – sonication method using soya lecithin and cholesterol as phospholipids. Four different formulations (CL1, CL2, CL3, and CL4) were prepared by taking different drug to lipid ratios. The prepared formulations were evaluated for particles size, surface potential, entrapment efficiency, Invitro release, drug polymer interaction.Particle size of all formulations was in the range of 300-470 nm and 110-240 nm; and the entrapment efficiencies were in the range of 75-85 % and 44-70 % for nanoparticles and liposomes respectively. From the formulations CNP3 and CL3 were selected as best formulations by considering the size, entrapment efficiency and release profiles. Pharmacokinetic parameters of the CNP3 and CL3 formulations were evaluated in rat. CNP3 and CL3 formulations were evaluated for hepatoprotective activity in CCl4 induced liver toxicity model and drug levels in different tissues including liver were determined. Formulation CNP3 showed better in vivo performance compared to CL3, curcumin IV and oral solutions. High liver levels of drug were achieved by the nanoparticular formulation (CNP3).