Liposomal Xanthone: polymer effect on the physicochemical properties of the liposomes and the antiallergic potential

• Grant number: 15/22373-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): January 01, 2016
• Effective date (End): July 31, 2016
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Rose Mary Zumstein Georgetto Naal
• Grantee: Bianca Bueno Fontanezi Dias Mello
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Mangiferin (Mgf), a C-glucosyl-xanthone, is a natural substance present in several plants, including the Mangifera Indica L. (known as the Mango tree). In Cuba, Mgf is found as a major compound of Vimang®, an extract patterned and registered by the Cuban Health Regulatory Authorities as anti-inflammatory phytoremediation. Other important biological activities, such as antiviral, anti-tumor, and anti-allergic have been reported for Mgf, being the last one our focus of interest, in the function of the growing number of allergic individuals in the whole world. In animal allergy models, Mgf significantly reduces the levels of IgE, anaphylactic reactions, and cutaneous reactions induced by histamine, as well as inhibits the proliferation of lymphocytes, which puts it in evidence as a promising compound in the treatment of allergies. Despite the pharmacological potential of Mgf, part of its therapeutic efficiency is wasted due to its low water solubility and susceptibility to photo-degradation, or chemical oxidation in solution, as well as rapid elimination from the body. These problems restrict its use as a Phyto molecule but can be overcome by the incorporation of liposomes, which are excellent drug nanocarriers due to their biocompatibility and versatility in the adjustment of their lipid composition and their physical-chemical properties. The technology of liposomes, acquired over the years, has been applied to photo molecules for use in diverse therapeutic segments, such as chemotherapeutic drugs, antibacterials, antioxidants, and others. In the case of polyphenols, the majority of liposomal formulations have been developed to be used as antioxidants, which justifies our interest in the study of a liposomal formulation, containing Mgf, to be used as the antiallergic one. Studies report that the efficiency of polyphenols increases when incorporated in liposomes. However, encapsulation efficiency is low, and a challenge to be overcome, seeing as it depends on the structure of the bioactive, the lipid composition, the bioactive: lipid ratio, and the form by which the liposome is prepared. Moreover, the possibility of using the liposomal bioactive by systemic administration, through the parenteral route requires the modification of the liposomal surface with proteins, polysaccharides, or polymers that prevent the attack of blood proteins and the premature elimination of the liposome by the immune system. The polymer polyethylene glycol (PEG) is considered a good option for this proposition, seeing as it is soluble in water, non-toxic, biocompatible and FDA approved for dermal, oral, and intravenous use in humans. Recent results obtained by our group showed that DMPC:DOTAP: COL liposomes incorporate approximately 30% of the Mgf, improving the bioavailability and the antiallergic potential. These results opened perspectives for new studies with modifications in the liposomal compositions aiming to contribute to the development of a physical-chemically stable formulation, with greater efficiency of Mgf incorporation and longer time in the systemic circulation. It is highlighted that, despite its broad pharmacological properties, Mgf is still little explored in studies concerning the incorporation in liposomes, which reaffirms the relevance of this study. As such, the aim of this study is to increase the encapsulation efficiency of Mgf through variations in the lipid composition of the liposome and in the bioactive: lipid ratio. Furthermore, it is intended to insert the PEG polymer in the liposomal composition and evaluate its influence in the incorporation of the bioactive. Besides the efficiency of incorporation, physical-chemical properties will be explored, such as size, stability, in vitro release rate, the phase transition temperature of the lipid, toxicity, and antiallergic potential. The success of this study may be useful in the use of Mgf for diverse therapeutic ends, in addition to the antiallergic one. (AU)