Title:Assessment of Exenatide loaded Biotinylated Trimethylated Chitosan/HP-
55 Nanoparticles
Volume: 19
Issue: 1
Author(s): Hejian Guo*, Xuehui Yan, Hao Tang and Xiaoyan Zhang
Affiliation:
- Department of Pharmacy, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, PR China
Keywords:
Exenatide, biotin, trimethylated chitosan, nanoparticles, oral delivery, type 2 diabetes mellitus.
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.