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Incorporation of mangiferin in cyclodextrins for biological aplications: effects of pH, buffer, ionic strenght and biliar salt

Grant number: 15/19251-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2015
Effective date (End): November 30, 2016
Field of knowledge:Health Sciences - Pharmacy
Principal researcher:Rose Mary Zumstein Georgetto Naal
Grantee:Bruna Carolina Massarioli
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Allergic diseases are growing at an unprecedented rate and represent a public health problem for developed or developing countries. The clinical manifestations of allergic diseases include asthma, rhinitis, food allergies, and insect allergies, among others. However, the respiratory symptoms are the most common, affecting up to 30% of the world population. Statistics from the World Health Organization in the year 2015, estimate a population of over 400 million allergic, which highlights the challenge of finding new drugs or antiallergic formulations effective in the treatment of allergies. The mangiferin (Mgf), a C-glycoside-xanthone of the flavonoid class provides wide pharmacological properties, including anti-allergic one. However, this bioactive have low solubility in water and susceptibility to chemical oxidation or photodegradation, in solution, which justify its incorporation into nanocarriers such as cyclodextrins (CDs). The molecular encapsulation of biologically active compounds via inclusion complexes with cyclodextrins is widely used in pharmaceutical applications. However, few studies have explored the influence of the environment such as the nature of the solvent, buffer composition, pH, or salt effect on the formation of these complexes. It is crucial to mention that the equilibrium formation of inclusion complexes can be displaced depending on the mentioned parameters, and for this reason they must be considered mainly in terms of practical application of such complexes in humans. In the case of an oral formulation, the complex must release the drug in the intestines to cross the biological barrier, fall into the systemic circulation and reach the target of interest. In this context, bile salts in the intestine play an important role in function of affinity for the CD cavity and easy displacement of the drug. The magnitude of this displacement depends on the pH, bioactive structure, CD type and proportion of bile salt in relation to bioactive. Therefore, this work intend to investigate the influence of pH, buffer type, ionic strength and the presence of bile salts on the mangiferin incorporation in ²-CD, and hydroxypropyl-²-CD, in order to contribute to the development of pharmaceutical formulations containing Mgf, a potentially bioactive against allergies and other diseases. The physico-chemical properties of Mgf incorporated in CDs will be correlated with allergy potential, in vitro, of mangiferin that it will be evaluated by degranulation of mast cells stimulated by antigen, according to the biosensor model based on RBL-2H3 mast cells line.

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