Co-delivery of saxagliptin and dapagliflozin by electrosprayed trilayer poly (D,l-lactide-co-glycolide) nanoparticles for controlled drug delivery

Abstract

Coaxial electrospray is advantageous for the production of multidrug-releasing nanocarriers because it permits precise control over particle size, inhibits initial burst release, and offers moderate preparation conditions. In this study, a single-step coaxial electrospray technique is presented that achieves over 90 % co-encapsulation of the saxagliptin and dapagliflozin, two drugs treating type 2 diabetes, into biodegradable poly (d,l-lactide-co-glicolide) (PLGA) nanoparticles. Scanning electron microscopy reveals spherical and smooth shapes with diameters ranging from 534.8 to 708.6 nm. Transmission electron microscopy revealed clear core–shell and trilayer nanostructures. Fourier transform infrared spectroscopy confirmed the presence of PLGA, saxagliptin, and dapagliflozin in all the evaluated formulations. The results of the drug release investigation indicated the prolonged and regulated release of saxagliptin and dapagliflozin from bi- and trilayer structures, as compared to monolayer particles. Computational modelling showed good agreement with the experimental drug release profile in vitro. Further, cytotoxicity assay demonstrates that the formulated nanoparticles display good cytocompatibility. This study indicates that with the controllable and distinctive sustained release profiles, the hybrid nanoparticle-based drug delivery system can effectively co-encapsulate multiple drugs treating type 2 diabetes in a protectively shell of PLGA for therapeutically-benefit controlled release.