Synergistic Antitumor Potency of a Self-Assembling Peptide Hydrogel for the Local Co-delivery of Doxorubicin and Curcumin in the Treatment of Head and Neck Cancer

Combination therapy has been conferred
with manifold assets leveraging
the synergy of different agents to achieve a sufficient therapeutic
outcome with lower administered drug doses and reduced side effects.
The therapeutic potency of a self-assembling peptide hydrogel for
the co-delivery of doxorubicin and curcumin was assessed against head
and neck cancer cells. The dual loaded peptide hydrogel enabled control
over the rate of drug release based on drug’s aqueous solubility.
A significantly enhanced cell growth inhibitory effect was observed
after treatment with the combination drug-loaded hydrogel formulations
compared to the respective combination drug solution. The synergistic
pharmacological effect of selected hydrogel formulations was further
confirmed with enhanced apoptotic cell response, interference in cell
cycle progression, and significantly altered apoptotic/anti-apoptotic
gene expression profiles obtained in dose levels well below the half-maximal
inhibitory concentrations of both drugs. The in vivo antitumor efficacy
of the drug-loaded peptide hydrogel formulation was confirmed in HSC-3
cell-xenografted severe combined immunodeficient mice and visualized
with μCT imaging. Histological and terminal deoxynucleotidyl
transferase dUTP nick end labeling assay analyses of major organs
were implemented to assess the safety of the topically administered
hydrogel formulation. Overall, results demonstrated the therapeutic
utility of the dual drug-loaded peptide hydrogel as a pertinent approach
for the local treatment of head and neck cancer.