Supramolecular systems of sucrose glycerate devatives studied by means of fluorescent techniques

FONDECYT 1120196 PROYECTO Finalizado

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Publicaciones: Sandoval, C., Arriagada, F.S., De la Fuente, J.R., Sanchez, S.A., Morales, J., Pizarro, N., Nonell, S., Gunther, G., "Synthesis, Physical Chemical and Photophysical Characterization of 4-(1-pyrenyl)-butyl-α-D-mannopyranoside", Journal of the Brazilian Chemical Society, 27(2), 402-410, 2016. C. Sandoval, A. Ortega, S. A. Sanchez, J. Morales, G. Günther, , “Structuration in the interface of direct and reversed micelles of sucrose esters, studied by fluorescent techniques”, Plos One 10(4): e0123669. doi:10.1371/journal , 2015.

Dr. Germán Günther Sapunar

PROPOSAL ABSTRACT:

Liposomes are very good candidates for drug carrier therapy, but in order to be successfully employed several difficulties must be overcome: rapid clearance from the blood stream; low drug accumulation in targets and uncontrolled drug release from the carrier before reaching the target organ. Additionally, drug delivery systems based on liposomes can be stated as efficient only when they have good colloidal, chemical and biological stability. A major progress in this area related with biological stability was the design of liposomes coated with the synthetic polymer,
polyethylene glycol (PEG). Pegylated liposomes have a significant longer half-life in the blood stream than conventional liposomes. This behavior is due to the presence of a hydrated environment around the liposomes which provides a steric barrier to the recognition and clearance by the reticuloendothelial system. References in the literature and our own studies clearly indicate that the presence of sucrose moieties on the surface of the liposome confer steric stabilization. Consequently the use of sucrose derivatives on liposome fabrication can be an interesting improvement for drug delivery purposes.
Non-ionic surfactants, specifically polyhdroxylated ones derived from sugars, have shown to be an excellent alternative for commonly used detergents of non-biological origin. Natural and synthetic biosurfactants (fatty acid glycoside esters or alkyl glycoside, with high or low lo molecular weight) are of great interest in the oil, food, cosmetic, and pharmaceutical industries because of their physicochemical and biological properties,. Even more, several glycosides have antimicrobial activity and can be useful in both clinical and veterinary medicine. A particularly interesting group of surfactants are the fatty acid esters of monosaccharides and disaccharides. Considered as the synthetic analog of glycosides, this type of surfactants has unique properties: they are non-toxic, skin compatible, non-polluting and biodegradable. We propose to synthesize a new type of surfactant, similar to glycoglycerolipids structure. As spacer between sugar and hydrophobic chain we are going to use glyceric acid. The esterification of diacylglyceric acid with sucrose under Mitsunobu conditions will yield 6-O-Sucrose diacylglycerate. This surfactant will have cylindrical topology, maintaining several properties of sucrose esters, but with a shape favoring the formation of bilayers.
According to our previous published studies, the presence of the bulky and highly hydroxylated sucrose head on the liposomes confers an important degree of structuration to the water near the bilayer. For us this observation is very relevant and our hypothesis is that vesicles of 6-O-sucrose diacylglycerates and mixed vesicles/liposomes (with DODAC, POPC or DPPC) will behave similar to the pegylated liposomes, with an enhanced stability and resistance to solubilization. In this work, the main physical chemical properties of pure 6-O-sucrose and mixed unilamellar vesicles will be studied. To accomplish these, diacylglycerates dervatives of lauric and palmitic acid will be synthesized, using some of the procedures previously employed by our group. Steady state, time resolved spectroscopic methods and biphotonic fluorescence microscopy will be employed to determine properties like micropolarity, microviscosity, transition temperature, and the existence of micro-domains in the membranes. The resistance to solubilization of liposomes in the presence of ionic and non-ionic detergents will be determined by spectroscopic methods and size determinations.
The results obtained from this proposal will contribute to achieve a deeper knowledge of the behavior of bilayer where the surface is blocked by sugar. Knowledge of properties such as
stability and permeability of these systems will help in the implementation of technological applications. One interesting application of this studies is the possibility to target antibiotics in
bacterial infections. It is known that pathogens bind to carbohydrates displayed on mammalian cells they will infect (the so-called “sweet tooth”). Protein-sugar interactions between the bacteria and the host cell are a crucial first step in the infectious process.