Polyester-based nanoparticles for the controlled release of bioactive coumarinic derivatives

Abstract

Listen

Translate article

Event Abstract Back to Event Polyester-based nanoparticles for the controlled release of bioactive coumarinic derivatives Ines Msolli1, 2, Frederic Chaubet1, Raoui Mounir Maaroufi2 and Christel Barbaud1 1 Galilee institute, LVTS, France 2 ISBM, LGBBV, Tunisia Introduction: Advancement in polymer science and engineering led to new polymers for controlled delivery of therapeutic drugs [1]. Poly([R,S]-3,3-dimethylmalic acid) (PDMMLA) and its hydrophobic derivatives can be considered as a family of promising polymers. PDMMLA is polyester synthesized for temporary therapeutic applications. Bioactive coumarinic derivatives, such as warfarin, present biological activities related to the cardiovascular field [2]. The encapsulation of a coumarinic derivative and its controlled delivery would be a relevant application of PDMMLA. Thus we first tried to encapsulate warfarin as a coumarinic model drug to optimize the controlled release settings. Experimental Part: A series of amphiphilic statistical and block copolyesters with different carboxylic acid/hexylic ester proportion: 70/30, 50/50 and 30/70 (mol/mol) belonging to the poly([R,S]-3,3-dimethylmalic acid) (PDMMLA) family have been synthesized [2],[3]. Polymer nanoparticles were further prepared by a nanoprecipitation solvent-evaporation method, and characterized by Transmission Electronic Microscopy (TEM) for nanoparticles morphology and dynamic light scattering for size and zeta potential studies.Controlled release of warfarin as a coumarinic drug model was followed by reversed-phase HPLC. Results: Statistical polymer with 30% of carboxylic acid and 70% of hexylic ester was choosen to investigate warfarin encapsulation by nanoprecipitation method and controlled release efficiency. TEM analysis evidenced spherical nanoparticles (Figure 2), which present an average size in physiological medium of about 80 nm (with a slight evolution of the size distribution over the study (28 days). The release of warfarin in a phosphate buffer saline at pH 7.4 and 37°C was monitored with reversed-phase HPLC over 28 days. The release followed a zero-order kinetics. Conclusion: We prepared a copolyester PDMMLAH30-co-Hex70 able to steadily release warfarin under simulated physiological conditions over 28 days. First results evidenced this polymer as a promising candidate for the delivery of bioactive coumarinic derivatives.