Selective Anticervical Cancer Injectable and Self-Healable Hydrogel Platforms Constructed of Drug-Loaded Cross-Linkable Unimolecular Micelles in a Single and Combination Therapy.

Abstract

In the face of severe side effects of systemic chemotherapy used in cervical cancer, topical selective drug carriers with long-lasting effects are being sought. Hydrogels are suitable platforms, but their use is problematic in the case of delivery of hydrophobic drugs with anticancer activity. Herein, hydrogels constructed of unimolecular micelles displaying enhanced solubilization of aromatic lipophilic bioactive compounds are presented. Star-shaped poly(benzyl glycidyl ether)-block-poly(glycidyl glycerol ether) with an aryl-enriched core show high encapsulation capacity of poor water-soluble nifuratel and clotrimazole. Nifuratel attained selectivity against cervical cancer cells, whereas clotrimazole preserved its original selectivity. The combination of unimolecular micelles loaded with both drugs provided synergism; however, they were still selective against cervical cancer cells. The cross-linking of drug-loaded unimolecular micelles via dynamic boronic esters provided injectable and self-healable hydrogel drug carriers also displaying synergistic anticancer activity, suitable for intravaginal administration and assuring the effective coverage of the afflicted tissue area and efficient tissue permeability with hydrophobic bioactive compounds. Here, we show that the combination of star-shaped polyether amphiphiles and boronic ester cross-linking chemistry provides a new strategy for obtaining hydrogel platforms suitable for efficient hydrophobic drug delivery.