Pyrvinium nanosuspension: preparation, physicochemical characterization and in vitro activity evaluation

• Grant number: 20/12634-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2021
• End date: May 31, 2022
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Nádia Araci Bou-Chacra
• Grantee: Guilherme Souza Macário
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cancer is a disease with a high mortality rate, victimizing millions worldwide each year, among the most lethal is colorectal cancer, also known as colon cancer. Treatment effectiveness is greatly determined by the primary containment of the disease, which can be achieved through surgical or medicative means, once the earlier the disease is detected, the greater are chances of treatment success. Currently available procedures have severe side effects and are extremely invasive. Pyrvinium, a Food and Drug Administration approved anthelmintic drug, has been presented as a promising alternative on anticancer treatment, making its repositioning plausible. Its method of action is attributed to the inhibition of the Wnt/beta-catenin signaling pathway, an important mechanism of carcinoma development, as well as inhibition of autophagy promoting pathways, vital for the survival of cells under hypoglycemia. However, pyrvinium presents low water solubility, bioavailability, and systemic absorption, factors that would make its use as an anticancer treatment less desirable. Given this challenge, nanotechnology shows itself as an innovative method to solve these inherent problems of the drug. Among these nano strategies nanocrystals are, arguably, the most elegant, giving the drug greater dissolution speed, bioavailability, and bioadhesion. Nanocrystals can be synthesized through a variety of methods, among them, solvent-antisolvent sonoprecipitation, a simple technique that uses ultrasound to improve homogenization and consistency in particle size. Thus, this project's goal is to develop, optimize, and assess the Physico-chemical properties of the pyrvinium nanosuspension. The following procedures will be performed: solvent selection, preparation of the nanosuspension, differential scanning calorimetry (DSC), determination of the hydrodynamic diameter (HD), polydispersity index (PI), zeta potential, efficiency in particle size reduction and evaluation of in vitro anticancer activity.