THERAPEUTIC POTENTIAL OF MILTEFOSINE LOADED IN POLYMERIC NANOPARTICLES FUNCTIONALIZED WITH HYALURONIC ACID IN A MURINE MODEL OF CRYPTOCOCCOSIS

• Grant number: 24/14735-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2025
• End date: April 30, 2029
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Kelly Ishida
• Grantee: Yuri Kelvin Silva Camacho Tavares
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cryptococcus neoformans is the causative agent of pulmonary cryptococcosis and meningitis and is classified as a critical priority pathogen by the World Health Organization mainly due to its high incidence in immunosuppressed patients, resulting in high mortality rates. The treatment of this mycosis is based on antifungal drugs; however, access to these drugs is still inadequate and sometimes inefficient, thus arising the need to discover new treatments. Miltefosine was implemented in 1980, initially as an antineoplastic agent, and in 2002 it was used as an antiparasitic in the treatment of leishmaniasis. The potential of miltefosine in the treatment of cryptococcosis has already been reported in the literature; however, some adverse effects are observed. Thus, the nanoencapsulation of drugs in polymers of natural origin, such as alginate, is an excellent alternative to mitigate adverse effects, in addition to being able to optimize pharmacodynamic and pharmacokinetic characteristics. The present study aims to obtain, characterize and evaluate the therapeutic potential of alginate nanoparticles loaded with miltefosine and functionalized with hyaluronic acid on neurocryptococcosis. The nanoparticles will be obtained by the external emulsion/gelation technique, the formulations will be characterized by microscopic, spectroscopic and physicochemical techniques and the therapeutic potential will be evaluated in a murine model of cryptococcosis with intranasal infection route.