| Grant number: | 19/04998-2 |
| Support Opportunities: | Regular Research Grants |
| Start date: | November 01, 2020 |
| End date: | April 30, 2023 |
| Field of knowledge: | Health Sciences - Pharmacy - Pharmaceutical Technology |
| Principal Investigator: | Gabriel Lima Barros de Araujo |
| Grantee: | Gabriel Lima Barros de Araujo |
| Host Institution: | Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| City of the host institution: | São Paulo |
Abstract
High dosages, unspecific targeting, clinical variability, high cost of formulations, poor water solubility, toxicity of cosolvents are recurrent problems in the development of antitumor drug therapies. Nanocrystal and Amorphous solid dispersions (ASD) are outstanding solid-state technologies suitable to overcome those problems helping to accelerate preclinical and clinical development and improve the rate of success. In this project, nanocrystals and amorphous solid dispersions of the antitumor drugs will be developed aiming at the development of better anticancer formulations with improved pharmaceutical properties. Flubendazole and niclosamide are well known antihelmintic drugs with very limited bioavailability that have been shown to pursue promising activity against a several of cancer models. Due to their poor solubility there are the urgent need for formulations that can enable administration and target delivery. Brilliant Blue G is a dye has been recently demonstrated to inhibit metastasis dissemination of neuroblastoma cells; however, the need of high dosage and it is association with undesirable and unspecific tissue targeting can compromise its use. Tyrosine Kinase Inhibitors (TKIs) are a new class of site-specific antitumor drugs that are revolutionizing the oral treatment of cancer. Marketed formulations of TKIs, however, presents clinical variability, high doses and pharmacokinetic variation due to their poor water solubility. New approaches to accelerate the development of new nanocrystal and ASD formulations such as advanced studies in solid state chemistry, thermal analysis, High-Energy X-ray Diffraction and Pair Distribution Function (PDF) will be explored to achieve efficient and stable formulations. A longer-range goal of this work is to contribute to the advancement of the use of nanocrystal and amorphous formulations in cancer therapy. The best formulations will be tested by using in silico, in vitro and in vivo models to demonstrate the proof of concept. (AU)
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