Synthesis of vildagliptin loaded acrylamide-g-psyllium/alginate-based core-shell nanoparticles for diabetes treatment

Abstract

Diabetes mellitus has become a major public health concern all over the world. Vildagliptin is one of the antidiabeticdrug that can overcome the existing problem of this prevalent disease. Present study aims to synthesize and investigate the role of vildagliptin-loaded core-shell nanoparticle of grafted psyllium and alginate (VG@P/A-NPs) in anti-diabetes application. FTIR, SEM, XRD, ¹³CNMR and zeta analyzer were used for characterization of the core-shell nanoparticles (VG@P/A-NPs). The synthesized acrylamide-grafted-psyllium was also optimized through varying grafting parameters such as acrylamide and ceric ammonium nitrate (CAN) concentration, time and temperature to obtain the maximum yield of acrylamide-grafted-psyllium. Rheological analysis of pure psyllium, grafted psyllium and alginate were also performed. For biological studies, the first cytotoxicity of grafted psyllium and VG@P/A-NPs were examined on human lung adenocarcinoma cell line A549 in which it was observed that VG@P/A-NPs did not exhibited any toxicity. The antidiabetic potential of VG@P/A-NPs was investigated by glucose uptake assay, using TNF-α induced insulin resistance skeletal cell model using mouse muscle L6 cell line. The insulin signaling impaired cell line displayed a highly significant (p < 0.0001) dose-dependent increase in glucose uptake after treatment with increasing doses of VG@P/A-NPs.The drug release behavior of VG@P/A-NPs was examined at various pH and the highest drug release (98 %) was obtained at pH (7.4). The drug release kinetic data was following the Higuchi (R² = 0.9848) kinetic model, suggesting the release of drug from vildagliptin-loaded grafted psyllium-alginate core-shell nanoparticles (VG@P/A-NPs) as a square root of time-dependent process and diffusion controlled. This study provides an economical and environment-friendly approach towards the synthesis of VG@P/A-NPs with antidiabetes applications.

Keywords: Alginate; Anti-diabetes; Core-shell nanoparticles; Psyllium; Vildagliptin.