Selective Anticervical
Cancer Injectable and Self-Healable
Hydrogel Platforms Constructed of Drug-Loaded Cross-Linkable Unimolecular
Micelles in a Single and Combination Therapy
posted on 2024-03-15, 16:06authored byMonika Gosecka, Mateusz Gosecki, Piotr Ziemczonek, Malgorzata Urbaniak, Ewelina Wielgus, Monika Marcinkowska, Anna Janaszewska, Barbara Klajnert-Maculewicz
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.