Evaluation of the potential of mucoadhesive precursor systems of liquid crystals for nasal administration of rifampicin applicable on the optimization of tuberculosis therapy

• Grant number: 15/00023-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): May 01, 2015
• Effective date (End): July 31, 2018
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Marlus Chorilli
• Grantee: Kaio Pini Santos
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated scholarship(s): 16/20622-4 - Biological activity and pharmacokinetic profile of rifampicin incorporated into mucoadhesive crystal liquid precursor system in preclinical animal model of tuberculosis, BE.EP.DR

Abstract

Tuberculosis (TB) is the major bacterial infectious disease in the world, leading to annual deaths of thousands of people and causing global economic losses of about 12 billion dollars a year. Only one drug was developed against multidrug-resistant strains since 1960 (bedaquiline) and the emergence of multi-drug-resistant cases of TB makes the current treatment ineffective. Rifampicin (RIF) is a first choice drug for the treatment of TB used since 1966. Typically, this drug is administered orally, thus it is susceptible to pre-systemic metabolism and drug interactions with other drugs, which significantly reduces their serum levels, and for other drugs as well; this may reduce the effectiveness of the treatment and increase the risk of resistance. Thus, the use of nanostructured delivery systems and alternative routes of administration may be attractive strategies for the administration of RIF. The nasal route has received special attention as a promising route for systemic drug delivery, since it presents epithelium with numerous microvillosities and large surface area, which facilitates the absorption of drugs. Furthermore, the anatomy of the nasal cavity provides access to the central nervous system (CNS), extremely interesting aspect in cases of tuberculous meningitis. Among the promising nanostructured systems for RIF incorporation focusing nasal administration, we highlight the mucoadhesive liquid crystal precursor systems (LCPS). Due to the high viscosity of some areas of these systems, they can promote the formulation fixation to a desired site of action after the administration and in situ formation, which might be interesting for the administration of RIF, to increase its attachment in the nasal region, facilitating its systemic absorption and interface with the CNS. Thus, the aim of this project is to study the potential of mucoadhesive LCPSs for nasal administration of RIF in the optimization of TB therapy, with in vitro and in vivo evaluation of its security and activity. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANTOS, KAIO PINI; RODERO, CAMILA FERNANDA; RIBEIRO, CAMILA MARINGOLO; GREMIAO, MARIA P. D.; PECCININI, ROSANGELA GONCALVES; PAVAN, FERNANDO ROGERIO; PEARCE, CAMRON; GONZALEZ-JUARRERO, MERCEDES; CHORILLI, MARLUS. Development of a Mucoadhesive Liquid Crystal System for the Administration of Rifampicin Applicable in Tuberculosis Therapy. LIFE-BASEL, v. 12, n. 8, p. 21-pg., 2022-08-01. (18/23430-4, 15/00023-6)