pH sensitive N-succinyl chitosan grafted polyacrylamide hydrogel for oral insulin delivery

• Published in: Carbohydrate polymers 2014-11, Vol.112, p.627-637
• Main Authors: Mukhopadhyay, Piyasi, Sarkar, Kishor, Bhattacharya, Sourav, Bhattacharyya, Aditi, Mishra, Roshnara, Kundu, P.P.
• Format: Article
• Language: English
• Subjects: Acrylic Resins - chemistry; Administration, Oral; Animals; Applied sciences; Biological and medical sciences; Biological Availability; Chitosan - chemistry; Diabetes Mellitus, Experimental - drug therapy; Drug Carriers - administration & dosage; Drug Carriers - adverse effects; Drug Carriers - chemistry; Exact sciences and technology; General pharmacology; Hydrogel; Hydrogel, Polyethylene Glycol Dimethacrylate - administration & dosage; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry; Hydrogen-Ion Concentration; Insulin - administration & dosage; Insulin - chemistry; Insulin - pharmacokinetics; Liver Function Tests; Male; Medical sciences; Mice; Microscopy, Electron, Scanning; Natural polymers; Oral insulin delivery; pH sensitivity; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; S-chitosan; Starch and polysaccharides; Toxicity Tests
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2014.06.045

•pH sensitive, mucoadhesive, N-succinyl chitosan graft polyacrylamide hydrogel preparation.•Good insulin encapsulation efficiency with pH sensitive sustained release.•Significant hypoglycemic effects in diabetic mice producing relative bioavailability of >4.4%.•No systemic toxicity at peroral administration. pH sensitive PAA/S-chitosan hydrogel was prepared using ammonium persulfate (APS) as an initiator and methylenebisacrylamide (MBA) as a crosslinker for oral insulin delivery. The synthesized copolymer was characterized by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) study; morphology was observed under scanning electron microscope (SEM). The PAA/S-chitosan with ∼38% of insulin loading efficiency (LE) and ∼76% of insulin encapsulation efficiency (EE), showed excellent pH sensitivity, retaining ∼26% of encapsulated insulin in acidic stomach pH 1.2 and releasing of ∼98% of insulin in the intestine (pH 7.4), providing a prolonged attachment with the intestinal tissue. The oral administration of insulin loaded PAA/S-chitosan hydrogel was successful in lowering the blood glucose level of diabetic mice. The bioavailability of insulin was ∼4.43%. Furthermore, no lethality or toxicity was documented after its peroral administration. Thus, PAA/S-chitosan hydrogel could serve as a promising oral insulin carrier in future.