Madihally Sundararajan V, Pantelogianis Angela, Toner Mehmet
School of Chemical Engineering, Oklahoma State University, Stillwater, Oklahoma, USA.
J Surg Res. 2006 Sep;135(1):187-94. doi: 10.1016/j.jss.2006.01.029. Epub 2006 Apr 17.
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.
皮下注射小剂量胰岛素已显示出对烧伤诱导的肌肉萎缩和伤口愈合具有有益作用。为改进胰岛素治疗在临床环境中的应用方法，本研究在20%总体表面积烧伤大鼠模型中，研究了使用pH响应性聚（甲基丙烯酸-g-乙二醇）（P（MAA-g-EG））水凝胶口服递送胰岛素的效果。P（MAA-g-EG）在内部合成，并进行了体外胰岛素释放特性研究。对体重80-150 g的幼鼠进行15-20%总体表面积烧伤，并使用明胶胶囊包裹的含胰岛素水凝胶治疗3天。剂量调整为每100克体重匹配0.25 U（第1天）、0.5 U（第2天）和1.0 U（第3天）。所有动物饲养在代谢笼中，在烧伤后4至15天监测其身体活动、体重、食物消耗、水摄入量、循环葡萄糖水平和尿酪氨酸含量。结果表明，口服递送的胰岛素恢复了烧伤大鼠的体重并影响伤口愈合，类似于皮下给药。测量的葡萄糖水平显示干扰明显较小，表明有可能增加剂量。总之，使用pH响应性水凝胶口服胰岛素可显著抑制肌肉萎缩。
