Enhanced antitumor efficacy of lapachol-loaded nanoemulsion in breast cancer tumor model

• Main Authors: Sued Eustáquio Mendes Miranda, Janaína de Alcântara Lemos, Renata Salgado Fernandes, Juliana de Oliveira Silva, Flaviano M. Ottoni, Danyelle M. Townsend, Domenico Rubello, Ricardo José Alves, Geovanni Dantas Cassali, Lucas Antônio Miranda Ferreira, Andre Luis Branco de Barros
• Format: Article
• Language: English
• Published: Elsevier 2021-01-01
• Series: Biomedicine & Pharmacotherapy
• Subjects: Lapachol; Nanoemulsion; Antitumor activity; Breast cancer; Radiolabeling
• Online Access: http://www.sciencedirect.com/science/article/pii/S0753332220311288

Lapachol (LAP) is a natural compound with various biological properties, including anticancer activity. However, its clinical application is limited due to the low aqueous solubility and potential adverse side effects. Nanoemulsions are drug delivery systems that can assist in the administration of hydrophobic drugs, increasing their bioavailability and protecting from degradation. Thus, this study aimed to prepare a LAP-loaded nanoemulsion (NE-LAP), and evaluate its antitumor activity. For this purpose, the nanoemulsion was prepared using a hot homogenization method and characterized morphologically by cryogenic transmission electron microscopy (cryo-TEM). Mean diameter, polydispersity index, and zeta potential was evaluated by DLS, encapsulation efficiency was measured by HPLC. Moreover, the short-term storage stability, the drug release and hemolysis in vitro was determined. Additionally, pharmacokinetic, toxicology and toxicity properties of99mTc-NE-LAP were evaluated in a breast cancer (4T1) tumor model. The cryo-TEM showed spherical globules, and the physicochemical characterization of NE-LAP showed a homogeneous stable nanoemulsion with a mean diameter of ∼170 nm, zeta potential of around −20 mV, and encapsulation greater than 85 %. In vitro studies validated that encapsulation did not impair the cytotoxicity activity of LAP. The nanoemulsion was successfully radiolabeled and 99mTc-NE-LAP showed prolonged blood circulation and tumor affinity was confirmed by tumor-to-muscle ratio. Moreover, NE-LAP showed higher antitumor activity than the free drug and the treatment did not result in any signs of toxicity. Therefore, these findings suggest that NE-LAP can be considered an effective strategy for cancer treatment.