Novel succinoylated carboxymethyl guar gum nanocarriers of glimepiride for controlling type-2 diabetes

Abstract

In this study, guar gum (GG) was chemically modified to its carboxymethyl derivative, which was then esterified with octenyl succinic anhydride (OSA) using a nucleophilic catalyst 4-dimethylaminopyridine (DMAP) to render the derivative amphiphilic characteristics. The carboxymethyl guar gum (CMGG) and succinoylated CMGG was characterized using Fourier transform infrared spectroscopy (FTIR) spectroscopy. The amphiphilic CMGG synthesized using DMAP/OSA ratio of 0.5:1 (CMGGOSA-I), was found to be non-toxic. The amphiphilic guar gum self-assembled in water to form nanocarriers with mean diameter of 430 ​nm and zeta potential of −19.0 ​mV. Transmittance electron microscope (TEM) image showed spherical nature of the developed CMGGOSA-I nanocarriers. In presence of amphiphilic CMGG, the aqueous solubility of glimepiride was enhanced by about 67-fold. The nanocarriers released glimepiride in simulated gastrointestinal fluids for a period of more than 24 ​h, following Higuchi's kinetics. Korsmeyer-Peppas modeling of the drug release data revealed that a combination of swelling and diffusion mechanism was operative in the event of drug release. In streptozotocin-induced diabetic rat model, the nanocarriers outperformed pure drug suspensions in terms of anti-diabetic activity, which lasted up to 24 ​h. Overall; the newly synthesized amphiphilic CMGG nanocarriers demonstrated controlled drug release properties and showed promise for controlling type-2 diabetes.

Keywords

• Guar gum
• Glimepiride
• Octenyl succinic anhydride
• Anti-diabetic efficacy