Transdermal Ionic Liquid Gel of Erlotinib for Localized Breast Cancer Therapy.

OBJECTIVE

Breast cancer is the second most diagnosed and the fourth leading cause of death among affected women. Here, we have formulated erlotinib (ETB) ionogel to enhance the solubility and transdermal permeation of ETB post-topical application in breast cancer. The presence of the lymphatic network and mammary fat layers in the breast augments drug accumulation, thus evading the side effects of systemic chemotherapy and the invasive nature of current localized treatments.

METHODS

Ionic liquid (IL) of choline geranate (CAGE) was synthesized via a salt metathesis reaction. ETB solubilized CAGE IL was subsequently transformed into an ionogel using Carbopol 980 NF and HPMC.

RESULTS

The HPMC ETB ionogel showed 71.04% permeation within 24 h and 64.3% drug release in 48 h following the Makoid-Banaker model. FTIR and SEM analysis confirmed the deeper dermal distribution of ionogel with the ability to maintain skin integrity. The ETB IL achieved the highest cytotoxicity in different breast cancer cell lines. The AUC, Cmax, and t1/2 of ETB ionogel increased by 1.19, 1.03, and 1.44-fold, respectively, than the ETB gel. The % tumor burden and tumor volume reductions were respectively calculated to be 2.4 and 2.3-fold lesser for ETB HPMC ionogel as compared to ETB HPMC gel. However, the % tumor growth inhibition increased by 1.2-folds for ionogel.

CONCLUSIONS

The improved in vivo efficacy and lower TEWL value depicted the non-toxic and permeable nature of ETB HPMC ionogel due to greater occlusivity, thus proving its transdermal yet localised effect in treating breast cancer.