Amphipathic methoxypolyethylene glycol-curcumin conjugate as effective drug delivery system useful for colonic diseases

Recently, supramolecular self-assembled core-shell nanostructures have emerged as advanced and notable drug delivery vehicles in biomedical arena for human health. Here, we have modified curcumin via Michael addition reaction with 3-mercaptopropionic acid followed by preparation of an amphiphatic conjugate employing hydrophilic polyethylene glycol monomethyl ether (mPEG). The synthesized compounds, curcumin-S-propionic acid (Cur-S) and curcumin-S-propionoyl-mPEG (Cur-S-mPEG), were spectroscopically characterized. Self-assembly of Cur-S-mPEG into micellar nanostructures was monitored by dynamic light scattering, which revealed the size of these nanostructures in the range of similar to 104 nm. Transmission electron microscopic analysis showed the size of these nanostructures similar to 26 nm. These micelles with hydrophobic pockets were then demonstrated to entrap hydrophobic therapeutics, ornidazole (Oz) and sulfasalazine (Sz), successfully with high efficiency. Drug-loaded formulations, Cur-S-mPEG(Oz) and Cur-S-mPEG(Sz), showed sustained release of drugs over a longer duration, particularly, a higher release at neutral pH 7.2 displaying the usefulness of the nanocarrier for colonic delivery. MTT assay performed on HEK 293 and Hep G(2) cells displayed the non-toxic nature of the nanocarrier on normal cells (HEK 293 cells) while toxic on cancer cells (Hep G2 cells). Graphic abstract