Release profile of insulin from pH-sensitive hydrogel and its hypoglycemic effect by oral administration

Abstract

The purpose of this study was to investigate the release profile and in vivo hypoglycemic effect of insulin (INS)-loaded pH-sensitive hydrogel (INS-TPM950) administrated by oral route. TPM950 was fabricated via a free polymerization method and its inner morphology was observed with a scanning electron microscope (SEM). INS was encapsulated into TPM950 by an adsorption method, and the in vitro release profiles of INS from INS-TPM950 were revealed in pH 1.2 and 6.8. To investigate the hypoglycemic effect of INS-TPM950, Male Wistar rats were used in modeling of diabetes mellitus by multiple intraperitoneal injection of alloxan. The in vivo hypoglycemic effect of oral INS-TPM950 was studied, and the optimal dosage was also determined. SEM photograph showed that abundant 3D meshes were distributed in the inner of TPM950 hydrogel. INS release profile suggested that only 18.2 ± 11.3% INS was released in pH 1.2, but over 88.8 ± 4.9% was delivered into phosphate buffer solution in pH 6.8. After injection to the diabetic rats, the released INS solution from INS-TPM950 exhibited an obvious hypoglycemic effect. Oral administration of 50.0 I.U./kg of INS-TPM950 showed a slow but effective hypoglycemic effect, and the lowest blood glucose level was reached to 47.5 ± 5.5% of the original level. Therefore, this formulation had a potential application in diabetes treatment via oral ingestion.

Research progress in the application of in situ hydrogel system in tumor treatment

“…The molecular skeleton of the materials made of pH-sensitive hydrogel contains a large number of dissociable groups. With the change of the environmental pH and the repulsion between the charges, the molecular chains are stretched, expanded and tangled with each other to form a hydrogel (Yan & Jin, 2012;Sahoo et al, 2013;Shi et al, 2016;Demirdirek & Uhrich, 2017;Rizwan et al, 2017). Such hydrogels usually contain -COOH or -NH 3 , which can form ions with different surrounding pH levels and promote effective shrinkage or expansion of the hydrogel.…”

Development of pH Sensitive Alginate/Gum Tragacanth Based Hydrogels for Oral Insulin Delivery

“…Although there are studies about formulation of pH responsive hydrogels for oral protein drug delivery such as chitosan based gels, ,,− synthetic polymer based gels, ,− and composite alginate hydrogels, ,,− there is still a need for design of hydrogel systems with better characteristics and more suitability for desired commercial usage. − In order to enhance the oral insulin bioavailability as well as to provide a biocompatible and stable environment for entrapped drug, not all biopolymers show the same effectiveness. It is altered regarding type of biopolymer and the design techniques …”