Liposomal formulation containing mangiferin: evaluation of the physical-chemical stability, influence of the bioactive and location in the biological membrane

• Grant number: 18/06220-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): June 01, 2018
• Effective date (End): August 31, 2020
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Rose Mary Zumstein Georgetto Naal
• Grantee: Amanda Bordonal Sostena
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Medicinal plants play an important role in the prevention and treatment of various diseases. According to the World Health Organization (WHO), around three fourths of the world population depend on traditional medication, especially herbs, to supply their health needs. In the developing countries, medications prepared from the local flora by traditional healers are the only available medications for the majority of the population and, in this context, attract the attention of researchers who seek to find new drugs and new formulations relevant to the curing of diseases. As an example of a medicinal plant, the popular Mangifera Indica L (commonly known as mango) can be mentioned, whose aqueous extract obtained from its bark stalks resulted in the extract Vimang®, which has been used in Cuba for the treatment of various diseases and pathologies. The phytochemical study of this extract led to the isolation of several phenolic compounds, such as mangiferin, galic acid, (+)-catequin, (-)-epicatequin, among others. However, mangiferin (Mgf) is the prevailing compound (~46%) and is responsible for important pharmacological properties, such as anticancer, antifungal, antidiabetic and anti-allergy. Despite of the pharmacological potential of Mgf part of its therapeutic effectiveness is wasted due to its low bioavailability and susceptibility to photodegradation or chemical oxidation, in solution, beyond its rapid elimination from the body, which restricts its use as phytomedication. These problems led us to study a physico-chemically stable liposomal formulation with a good incorporation efficiency of Mgf and viable for oral administration in the treatment of several diseases such as cancer and allergy. Although the greater efficacy of the polyphenols incorporated into the liposomes is notorious, it is also known that the encapsulation yield is low, and a challenge to be overcome. Previous studies conducted in our group using a lipid-based formulation dimyristoylphosphatidylcholine (DMPC) have resulted in low encapsulation efficiency of Mgf (about 28%) which led us to explore a new formulation based on the lipid phosphatidylcholine (PC) to which is expected to increase the incorporation of the bioactive due to the greater flexibility of the PC compared to the DMPC. This formulation should also contain the lipids phosphatidylethanolamine (PE) and cholesterol (COL) in the ratio PC: PE: COL (52:28:20) whose lipid composition mimics the biological membrane and allows to study, by means of photophysical techniques, the location of the bioactive in the biological membrane and its influence on membrane fluidity, which are important parameters to understand the mechanism of action and the pharmacological potential of the bioactive. The stability of the liposomal formulation will be monitored over time through physical-chemical properties such as size, polydispersity and Zeta potential. Such parameters will be reevaluated after lyophilization in the presence of cryoprotectants (sucrose and trehalose), and liposomal resuspension in aqueous medium. Finally, it is worth noting that, despite its wide pharmacological properties, Mgf is still little explored in studies concerning incorporation into nanocarrier systems, such as liposomes, which reinforces the relevance of this study for future biological applications and development of new pharmaceutical formulas for various purposes such as oral, ocular, dermal, respiratory and other treatments.