Antiproteolytic action of orally delivered insulin using pH-responsive hydrogels in a rat burn model

Subcutaneously delivered small doses of insulin has shown beneficial effects on burn injury-induced muscle wasting and wound healing. To improve the method of insulin treatment for clinical settings, this study investigated the effect of insulin delivered orally using pH-responsive poly(methacrylic-g-ethylene glycol) (P(MAA-g-EG)) hydrogels in a 20% total burn surface area rat burn injury model. P(MAA-g-EG) were synthesized in-house and insulin release characteristics were performed in vitro. Young rats weighing 80-150 g were subjected to 15-20% total body surface area burn injury and treated with insulin-containing hydrogels enclosed in gelatin capsules for 3 days. The dosage was adjusted to match 0.25 U (day 1), 0.5U (day 2), and 1.0 U (day 3) per 100 grams of body weight. All animals were housed in metabolic cages and their physical activity, body weight, food consumption, water uptake, circulating glucose levels, and urinary tyrosine content were monitored for 4 to 15 days after burn. Results show that the orally delivered insulin restored the body weight of burned rats and influenced wound healing, similar to subcutaneous delivery. Measured glucose levels showed significantly less perturbation, suggesting the possibility of increasing the dosage. In conclusion, muscle wasting can be significantly inhibited by the oral administration of insulin using pH-responsive hydrogels.