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Bioavailability and pharmacokinetics of zidovudine mucoadhesive solid dispersions and polymeric nanoparticles in rats

Grant number: 14/08044-0
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Start date: September 09, 2014
End date: February 08, 2015
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal Investigator:Maria Palmira Daflon Gremião
Grantee:Liliane Neves Pedreiro
Supervisor: Matilde Merino Sanjuán
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Institution abroad: Universitat de València, Spain  
Associated to the scholarship:13/01670-0 - Development of mucoadhesives solid dispersion and polymeric nanoparticles of zidovudine and biological interaction evaluation with intestnal mucosa, BP.DR

Abstract

Zidovudine (AZT) is the most widely used drug alone or in combination with other antiretroviral agents for the treatment of AIDS, caused by the HIV virus. The low AZT bioavailability is the great challenge to be overcome to optimize its performance in oral therapy, since its high rate of hepatic metabolism and low permeability results in the need for high doses of the drug, which often reach toxic plasma levels, causing serious side effects. There are numerous reasons for the choice of the oral route for drugs administration, including ease administration and total control by the patient, along with a wide flexibility in dosage. However, there are physiological differences along the gastrointestinal tract (GI tract) favoring the design of some dosage forms to be directed to specific segments. Thus, the AZT incorporation into drug delivery systems with mucoadhesive properties that protect the drug of the gastric medium, such as solid dispersions and polymeric nanoparticles, should ensure that intact drug reaches to the small intestine. One of the reasons that make it difficult for new drug delivery systems reach the commercial market is the lack of efficacy; therefore, the biopharmaceutical step, as a decision factor for the continuity or not in the development of a drug delivery system is crucial to the success in pharmaceutical research, and should be evaluated as far as possible. This step is crucial to evaluate the performance of these new delivery systems for drug bioavailability. Thus, this project proposes to evaluate the bioavailability and pharmacokinetics of zidovudine mucoadhesive solid dispersions and polymeric nanoparticles in rats. (AU)

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