Synthesis of lipid-modified copolymers based on caprolactone via enzymatic ring-opening polymerization and click chemistry and evaluation of their potential as vehicles in drug delivery

This research focuses on the application of click chemistry to the synthesis of amphiphilic lipidic copolymers with a target number of oleyl, cholesteryl, and linoleic pendant groups. The synthesis was performed using a two-step approach. In the first step, copolymerization of epsilon-caprolactone (CL) and alpha-azido-caprolactone (N3CL) was carried out using enzymatic ring-opening polymerization (eROP) catalyzed by Candida Antarctica lipase B (CALB). This resulted in copolymers with an average molecular weight of 9.53 kDa, each containing approximately seven azide groups per chain. Subsequently, click chemistry was utilized to react P(N3CL-co-CL) copolymers with propargylated lipidic compounds, achieving azide group consumption higher than 88%. These lipidic copolymers exhibited reduced crystallinity, as evidenced by their lower melting enthalpy values. In addition, these materials were evaluated for the fabrication of nanostructured vehicles for curcumin (Cur@NP) using the solvent emulsion-evaporation methodology. The lipidic copolymers demonstrated enhanced encapsulation efficiencies and drug loading capacities of 25 and 12%, respectively, tunable particle sizes in the range of 260-420 nm, and controlled release profiles over 30 h. Cur@NPs demonstrated notable antioxidant and antibacterial activities, particularly against Gram-positive bacteria such as Staphylococcus aureus, achieving efficiencies close to 50%. Enhanced curcumin encapsulation following modification of polycaprolactone, obtained via enzymatic ring-opening polymerisation, with lipidic moieties via click chemistry. image