Assessment of Exenatide loaded Biotinylated Trimethylated Chitosan/HP- 55 Nanoparticles

Abstract

Background: Exenatide(EXE) is an anti-hyperglycemic agent approved for treating type 2 diabetes by the Food and Drug Administration(FDA). However, twice-daily injection of exenatide is inconvenient for most of the patients.

Objective: In this study, biotinylated trimethylated chitosan(Bio-TMC) based nanoparticles were proposed to promote oral absorption of exenatide. Realizing the oral administration of exenatide is very important to alleviate patient suffering and improve patient compliance.

Methods: Bio-TMC was synthesized, and the chemical structure was characterized by Fourier transform infrared (FT-IR) spectroscopy and 1H NMR spectroscopy. Nanoparticles were prepared through polyelectrolyte interaction in the presence of sodium Tripolyphosphate (TPP) and hydroxypropyl methylcellulose phthalate (HP-55). Formulations were physically and chemically characterized. In vitro release was investigated in different pH media. In vivo antidiabetic activities of biotin modified and non-biotin modified chitosan were evaluated in db/db mice.

Results: EXE-loaded Bio-TMC/HP-55 nanoparticles were spherical in shape with a mean diameter of 156.2 nm and zeta potential of +11.3 mV. The drug loading efficiency and loading content were 52.38% and 2.08%, respectively. In vitro release revealed that EXE-loaded Bio-TMC/HP-55 nanoparticles were released faster in pH 1.2 than pH 6.8 (63.71% VS 50.12%), indicating that nanoparticles have enteric characteristics. Antidiabetic activity study revealed that after oral administration to diabetic mice, the relative pharmacological bioavailability (FPharm%) of the biotin modified nanoparticles was found to be 1.27-fold higher compared to the unmodified ones, and the hypoglycemic effect was also found to be better.

Conclusion: Bio-TMC/HP-55 nanoparticles are feasible as oral drug carriers of exenatide and have the potential to be extended to other drugs that are not readily oral, such as monoclonal antibodies, vaccines, genes, etc. These would be beneficial to the pharmaceutical industry. Further research will focus on the biodistribution of Bio-TMC/HP-55 nanoparticles after oral administration.

Keywords: Exenatide; biotin; nanoparticles; oral delivery; trimethylated chitosan; type 2 diabetes mellitus.