Norcantharidin Nanoemulsion Development, Characterization, and In Vitro Antiproliferation Effect on B16F1 Melanoma Cells

Abstract

Melanoma is a highly lethal type of cancer that has had an increase in incidence in the last decades. Nevertheless, current therapies lack effectiveness and have highly disabling side effects, which calls for new therapeutic strategies. Norcantharidin (NCTD) is an acid derivative with potential antitumor activity isolated from natural blister beetles. However, its solubility limitations restrict its use. To address this issue, we developed an oil-in-water nanoemulsion using commonly available cosmetic ingredients, which increased NCTD solubility 10-fold compared to water. The developed nanoemulsion showed a good droplet size and homogeneity, with adequate pH and viscosity for skin application. In vitro drug release studies showed a sustained release profile, ideal for prolonged therapeutic effects. Accelerated stability studies proved that the formulation was reasonably stable under stress conditions, with particle separation fingerprints, instability index, particle size, and sedimentation velocity analyses being conducted. To assess the therapeutic potential of the developed formulation, in vitro studies were conducted on melanoma B16F1 cells; results showed an IC50 of 1.026 +/− 0.370 mg/kg, and the cells’ metabolic activity decreased after exposure to the NCTD nanoemulsion. Hence, a new “easy-to-make” nanoformulation with therapeutic potential on melanoma cells was developed, as a possible adjuvant for future melanoma treatment.

Tumor-Infiltrating iNKT Cells Activated through c-Kit/Sca-1 Are Induced by Pentoxifylline, Norcantharidin, and Their Mixtures for Killing Murine Melanoma Cells

“…This biomolecule has antiangiogenic properties that are also linked to the induction of necrosis, and it mediates the migration and recruitment of plasmacytoid dendritic cells and ChemR23-dependent NK cells [48,49]. Therefore, treatment with NCTD at a dose of 3.0 mg/kg, in addition to inducing a cytotoxic pharmacological effect on tumor cells [17], may favor the migration of iNKT cells to the tumor site. Moreover, a significant part of the tumor-infiltrating lymphocytes is active (CD107a+) and presented immature markers under this treatment.…”

“…Another exciting substance for the adjuvant or neoadjuvant treatment of melanoma is norcantharidin (NCTD) [17]. Its antitumor effect has been extensively investigated in different types of malignant tumors.…”

Exploring Nanocarriers as Treatment Modalities for Skin Cancer

“…Martínez-Razo et al [228] developed the NEs to evaluate their potency against skin cancer treatment. In this study, norcantharidin-loaded oil-in-water NEs were prepared and evaluated the cytotoxic potential against B16F1 cells, and IC 50 was found to be 1.026 ± 0.370 mg/L, significantly lower than the control.…”

Ginger Oil Nanoemulsion Formulation Augments Its Antiproliferative Effect in Ehrlich Solid Tumor Model

“…The cracking of nanoemulsion occurs when the oil and water are separated and will not recombine. The creaming index (%CI) was calculated as follows [42,43]: %CI = (CC/CT) × 100 where CC = total height of cream layer and CT = total height of nanoemulsion.…”