Core shell micelles from biocompatible amphiphilic copolymers as nanoreservoirs in drug delivery systems

Abstract

Here, we have explored the micellar and phase behaviour of a biocompatible, nontoxic, commercially available, hydrophilic star shaped polyethylene oxidepolypropylene oxide (EO-PO) branched octablock copolymer Tetronic® 1107 (T1107; mol.wt.: 15000 g.mol-1, %PEO = 70, and HLB 18-23) in water and in aqueous NaCl solutions by viscosity, surface tension, fluorescence, cloud point (CP), dynamic light newlinescattering (DLS) and small angle neutron scattering (SANS). The copolymer being very hydrophilic shows weak surface activity and strong dependence on temperature showing nanosized stable core-shell micelles at higher temperature and/or in the presence of salt. Two hydrophobic, poorly water soluble antioxidants viz. curcumin and quercetin were loaded in the micelles and the solubility was investigated by UVspectrophotometry, showed marked enhancement in solubility. In vitro controlled release profiles of both the drugs from T1107 micelles were investigated and then analysed using different kinetic models, results demonstrated controlled drug release from micelles by the diffusion process. In vitro antioxidant activities of free as well as encapsulated drugs were evaluated by DPPH free radical scavenging, reducing capacity and superoxide anion radical scavenging methods, which showed enhanced antioxidant activity of micellar drugs as compared to free drugs. In vitro genotoxicity by tokinesis-blocked micronucleus (CBMN) assay was also performed for free and encapsulated drugs demonstrating beneficial effects of micellar materials on the genotoxicity of drugs. In vitro cytotoxicity of the drugs against CHOK1 and Caco-2 cell line were performed indicating comparable effects of both free and micellar drugs. In order to evaluate in vitro oral efficiency of free and micellar drugs, permeability across Caco-2 cell monolayer was determined and in vivo oral efficiencies were investigated by studying pharmacokinetic parameters and tissue distribution in Wistar rat after oral dosage of free and micellar drugs. In vitro oral efficiency