methylcellulose and Diabetes-Mellitus--Type-1

The purpose of this study was to fabricate a novel binary hydrogel, and the insulin-loaded hydrogel was used as rectal suppository to prevent type I diabetes. The binary hydrogel was synthesized via solution polymerization. Its structure was studied by Fourier transform infrared spectroscopy (FTIR) and Raman spectra. The swelling behaviors of binary hydrogels were revealed in pH 1.2, 6.8 and 7.4 buffers, respectively. Their inner morphologies were observed with a scanning electron microscope (SEM). Insulin (INS) was selected as a model drug and encapsulated into the binary hydrogels. INS release study was carried out in pH 7.4 buffer. The hypoglycemic effects of INS-loaded hydrogels were studied by rectal administration. FTIR and Raman spectra confirmed the obtaining of binary hydrogels. The hydrogel showed a high swelling ratio in pH 7.4 (rectum environment). SEM photographs illustrated that many micro-pores in the inner of binary hydrogels, which could accommodate abundant guest molecule (e.g. INS). INS release profile suggested that INS-loaded hydrogels could diffuse INS at a sustained manner. Animal studies proved that INS-loaded binary hydrogel had an obvious hypoglycemic effect. Therefore, it could be speculated that the binary hydrogel had a potential application on treating type I diabetes by rectal administration.

Topics: Acrylic Resins; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Hydrogels; Hypoglycemic Agents; Male; Methylcellulose; Rats, Sprague-Dawley; Rectum; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Suppositories; Thermogravimetry; X-Ray Diffraction

Diabetes is the fastest growing metabolic disease that fails to utilize glucose properly due to insulin deficiency or insulin resistance. Although several limited studies demonstrated non-invasive means of protein delivery, major hurdles for commercial success such as short half-life, enzymatic degradation and low bioavailability still remain to overcome. Methylcellulose (MC), a hydrophobically-modified cellulose derivative, forms temperature reversible gel in aqueous solution. However, as the gelling temperature of MC is higher than body temperature, it should be lowered to below body temperature for practical clinical application. In order to decrease gelling temperature and increase bio-compatibility and bio-elimination of MC, the molecular weight of MC was decreased using enzymatic degradation method and confirmed by gel permeation chromatography. Bio-elimination of low molecular weight (LMw) MC was confirmed with non-invasive live image and ex vivo experiment. The exenatide and FGF 21 were physically loaded 100% into LMwMC-based thermo-reversible gel and slowly released from gel with no initial bursts. Exenatide-loaded LMwMC gel showed reduction of blood glucose level for a week in type 1 diabetic animal model. FGF 21-loaded LMwMC gel reduced glucose level to normal condition and maintained over 10 days in type 2 diabetic animal model. LMwMC-based thermo-reversible and injectable hydrogel provides a strong potential to be efficient protein drug delivery system for the treatment of type 1 and type 2 diabetes.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Exenatide; Fibroblast Growth Factors; Gels; Hypoglycemic Agents; Male; Methylcellulose; Mice; Mice, Inbred BALB C; Molecular Weight; Peptides; Pharmaceutic Aids; Thermodynamics; Tissue Distribution; Venoms