Hyaluronic acid-coated nanoemulsions loaded with a hydrophobic ion pair of all-trans retinoic acid for improving the anticancer activity

  • Letícia Márcia da Silva Tinoco Federal University of Jequitinhonha and Mucuri Valleys, Faculty of Biological and Health Sciences, Department of Pharmacy
  • Flávia Lidiane Oliveira da Silva Federal University of Jequitinhonha and Mucuri Valleys, Faculty of Biological and Health Sciences, Department of Pharmacy
  • Lucas Antônio Miranda Ferreira Federal University of Minas Gerais, Faculty of Pharmacy, Department of Pharmaceutics
  • Elaine Amaral Leite Federal University of Minas Gerais, Faculty of Pharmacy, Department of Pharmaceutics
  • Guilherme Carneiro Federal University of Jequitinhonha and Mucuri Valleys, Faculty of Biological and Health Sciences, Department of Pharmacy
Keywords: All-trans-retinoic acid, Breast neoplasms, Drug delivery, Hyaluronic acid, Nanoemulsion

Abstract

All-trans retinoic acid (ATRA) has been studied for the treatment of cancer, including leukemia and breast cancer. This work aims to develop nanoemulsions (NE) loaded with a hydrophobic ion pair (HIP) of all-trans retinoic acid (ATRA) and a lipophilic amine, stearylamine (SA), and coated with hyaluronic acid (HA) to enhance anticancer activity and reducing toxicity. Blank NE was prepared by spontaneous emulsification and optimized prior to HIP incorporation. NE-ATRA was electrostatically coated with different concentrations of HA. Incorporation of ATRA-SA led to monodisperse NE with small size (129 ± 2 nm; IP 0.18 ± 0.005) and positive zeta potential (35.7 ± 1.0 mV). After coating with 0.5 mg/mL HA solution, the mean diameter slightly increased to 158 ± 5 nm and zeta potential became negative (-19.7 ± 1.2 mV). As expected, high encapsulation efficiency (near 100%) was obtained, confirmed by polarized light microscopy and infrared analysis. Formulations remained stable over 60 days and release of ATRA from NE was delayed after the hydrophilic HA-coating. HA-coated NE-ATRA was more cytotoxic than free ATRA for MDA-MB-231 and MCF-7 breast cancer cell lines, especially in the CD44 overexpressing cells. Blank coated formulations showed no cytotoxicity. These findings suggest that this easily-made HA-coated NE-ATRA formulation is a promising alternative for parenteral administration, thus improving the breast cancer therapy with this drug.

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Published
2018-12-20
How to Cite
Tinoco, L., Silva, F., Ferreira, L. A., Leite, E., & Carneiro, G. (2018). Hyaluronic acid-coated nanoemulsions loaded with a hydrophobic ion pair of all-trans retinoic acid for improving the anticancer activity. Brazilian Journal of Pharmaceutical Sciences, 54(4), e17361. https://doi.org/10.1590/s2175-97902018000417361
Section
Articles