Ms. Anna Zaritski, M.Sc. Candidate (Haifa Campus)
Poor aqueous solubility and permeability of drugs in biological fluids, is a common property of nearly 50% of the active pharmaceutical ingredients that are marketed today. Poorly aqueous-soluble drugs show limited gastrointestinal absorption and oral bioavailability. Moreover, inappropriate biodistribution profiles are associated with efficacy loss and adverse effects.
Polymeric micelles (PMs) are a nanotechnology platform used to overcome several of these biopharmaceutical drawbacks. They are formed upon the self-assembly of amphiphilic copolymers above the critical micellar concentration (CMC) and display a core-corona structure; the inner core is made of the hydrophobic blocks and can encapsulate hydrophobic cargos, while the outer corona of hydrophilic blocks stabilize the PM and reduces the recognition by the reticuloendothelial system that results in fast clearance. Moreover, the modification of the surface with ligands enables the targeting of the PM to specific cell populations.
In this work, we will report on the synthesis and characterization of a novel type of amphiphilic nanocarrier based on a backbone of galactomannan – a natural water-soluble polysaccharide composed of a (1–4)-linked β-D-mannose backbone with (1–6)-linked side chains of α-D-galactose in the ratio 1:4 that is isolated from Locust bean gum (LBG) and that binds different types of sugar receptors in cells – that is hydrophobized by the graft free radical polymerization of methyl methacrylate to form poly(methyl methacrylate) (PMMA) blocks. This modification confers the copolymers with self-aggregation properties. The different products were characterized by FTIR, 1H-NMR, and the CMC, particle size and size distribution by dynamic light scattering (DLS). The encapsulation capacity of a model drug was studied using the hydrophobic tyrosine kinase inhibitor imatinib. Finally, the interaction of the nanoparticles with cells that highly express glucose transporters was investigated on different tumor cells using light and confocal microscopy and flow cytometry analysis.
Prof. Alejandro Sosnik