Selection and optimization of nano-formulation of P-glycoprotein inhibitor for reversal of doxorubicin resistance in COLO205 cells.

ABSTRACT

OBJECTIVE: The prime objective of current work was to develop a strategy for preparation of combinational nano-formulation for reversal of drug resistance. METHODS: As a model system, doxorubicin (DOX)-resistant COLO205 cells were developed and validated. From co-treatment studies with DOX, curcumin was selected as it reversed DOX-resistance at lowest concentration. In an attempt to increase its solubility, curcumin was encapsulated into hydroxypropyl-ß-cyclodextrin (HP-ß-CD). Here, we propose that presence of stabilizer overcomes its low encapsulation efficiency. Thus, we evaluated curcumin encapsulation in HP-ß-CD in presence of different stabilizers and organic solvents. Finally, the effect of nanocurcumin with liposomal DOX was studied for reversal of resistance in COLO205 cells. KEY FINDINGS: In the process encapsulation, selective optimization of organic solvent by freeze-drying was found to be appropriate among other methods. From optimization studies with different organic solvent (acetone and dichloromethane) and stabilizer [polyvinyl alcohol (PVA) and Pluronics], HP-ß-CD-encapsulated curcumin prepared using acetone in PVA-stabilized dispersion increased encapsulation (60%) with size of ~40 nm. Prepared nano-curcumin reversed the DOX resistance effectively in combination with liposomal DOX. CONCLUSIONS: Curcumin reversed DOX resistance in COLO205 cells at low concentration and enhanced curcumin encapsulation in HP-ß-CD was noted in presence of PVA. Further, it was observed that prepared HP-ß-CD-encapsulated curcumin is equi-efficacious to nano-dispersed curcumin.