Synthesis of PLA-PEG Copolymers Containing Folic Acid and Fluorescein by Ugi Reaction

This work describes the synthesis of two poly(lactic acid)-b-poly(ethylene glycol) copolymers (PLA-b-PEG), one containing folic acid, a targeting ligand, and the other containing fluorescein, a marker, both important in drug delivery systems. The copolymerization was carried out using the Ugi multicomponent reaction, which is a one pot reaction that involves the condensation of four components, an aldehyde or ketone, an amine, a carboxylic acid and an isocyanide. For this, poly(lactic acid) was functionalized with an aldehyde group (PLA-CHO) and poly(ethylene glycol) with an amine (PEG-NH2) and a carboxylic acid group (PEG-COOH), to be used in the Ugi reactions. From Fourier transform infrared spectroscopy (FTIR), hydrogen nuclear magnetic resonance (1 H NMR) and ultraviolet-visible (UV-Vis) analyses, it was possible to confirm the synthesis of the block copolymers, in addition to the presence of both folic acid and fluorescein in the chemical structure of the materials. The work demonstrates that the Ugi reaction is an effective method to obtaining copolymers with different functionalities, and these materials have the potential to prepare micro and nanoparticles to be used in the controlled release of drugs.