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Pharmaco technological challenge for melittin microencapsulation in liposomes

Grant number: 06/04088-6
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): December 01, 2006
Effective date (End): April 30, 2009
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal researcher:Maria Helena Bueno da Costa
Grantee:Sérgio de Paula Moura
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Arthropod bites and stings are capable of inflicting injury, inciting allergic reactions, and transmitting systemic disease. Members of the Hymenoptera order are of particular importance because they are nearly ubiquitous in nature, and their stings may cause life-threatening allergic reactions. Stings from bees, wasps, and ants produce a variety of clinical and histological manifestations. Anaphylaxis following an insect sting is the most serious complication. For individuals with a specific allergy to Hymenoptera venom, the venom immunotherapy (VIT) may be a relatively effective treatment option. Treatments failures do however occur and VIT may cause frequent systemic allergic side effects, mainly in honeybee venom allergy persons. The Immunotherapy is expensive and time consuming. New strategies to improve safety and efficacy of this treatment are therefore of general interest. We propose here a systematic approach to study the basic and biotechnological problems related with the development of safe formulations of bee venoms within liposomes to be used in VIT. We intend to start studying the mainly molecular characteristics related to mellitin/lipid interactions. It is known, that mellitin (Mel) is the major toxic peptide in the European honey bee venom (50 % of the wet weight) and that it has a powerful hemolytic activity and it is responsible for local pain. The biotechnological challenge here is to chemically modify the mellitin molecule to permit its encapsulation within liposomes of natural phospholipids. The Mel biological toxicity will, probable, decrease by two reasons: 1. because the molecule will possibly lose its hemorrhagic activity through chemical modification and 2. the lipossomal encapsulation will avoid direct contact between Mel and the organism and, in addition, this vehicle has adjuvant characteristics. As a direct consequence it will be possible, in the future, to design a formulation for preventive (VIT) medicine.The idea is to work with the whole bee venom or its components mellitin and phospholipase. Here, in this first project, we will work with the mellitin. When analyzed together, these literature data, lead us to formulate and fundament our propositions: 1. To chemically modify the Mel tryptophan (19) and the Tyrosines (10 and 11) 2. To chemically modify the Mel NH2 terminus Lys 7, 21 and 23.3. To study the conformation of the Mel derivatives4. To study the presence or absence of interaction between Melmodified with natural membranes composed of natural phospholipids.5. To entrap the less active Melmodified.6. To do tolerance assay with mice.7. To propose an intelligent formulation containing Melmodified to be used in VIT. (AU)

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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)
SILVA, TATIANA C.; MOURA, SERGIO DE PAULA; RAMOS, HENRIQUE R.; DE ARAUJO, PEDRO S.; BUENO DA COSTA, MARIA H. Design of a Modern Liposome and Bee Venom Formulation for the Traditional VIT-Venom Immunotherapy. Journal of Liposome Research, v. 18, n. 4, p. 353-368, 2008. Web of Science Citations: 1.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.