Srivastava Rohit, Jayant Rahul Dev, Chaudhary Ayesha, McShane Michael J
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, India.
J Diabetes Sci Technol. 2011 Jan 1;5(1):76-85. doi: 10.1177/193229681100500111.
Minimally invasive glucose biosensors with increased functional longevity form one of the most promising techniques for continuous glucose monitoring. In the present study, we developed a novel nanoengineered microsphere formulation comprising alginate microsphere glucose sensors and anti-inflammatory-drug-loaded alginate microspheres.
The formulation was prepared and characterized for size, shape, in vitro drug release, biocompatibility, and in vivo acceptability. Glucose oxidase (GOx)- and Apo-GOx-based glucose sensors were prepared and characterized. Sensing was performed both in distilled water and simulated interstitial body fluid. Layer-by-layer self-assembly techniques were used for preventing drug and sensing chemistry release. Finally, in vivo studies, involving histopathologic examination of subcutaneous tissue surrounding the implanted sensors using Sprague-Dawley rats, were performed to test the suppression of inflammation and fibrosis associated with glucose sensor implantation.
The drug formulation showed 100% drug release with in 30 days with zero-order release kinetics. The GOx-based sensors showed good enzyme retention and enzyme activity over a period of 1 month. Apo-GOx-based visible and near-infrared sensors showed good sensitivity and analytical response range of 0-50 mM glucose, with linear range up to 12 mM glucose concentration. In vitro cell line studies proved biocompatibility of the material used. Finally, both anti-inflammatory drugs were successful in controlling the implant-tissue interface by suppressing inflammation at the implant site.
The incorporation of anti-inflammatory drug with glucose biosensors shows promise in improving sensor biocompatibility, thereby suggesting potential application of alginate microspheres as "smart tattoo" glucose sensors with increased functional longevity.
具有更长功能寿命的微创葡萄糖生物传感器是连续葡萄糖监测最有前景的技术之一。在本研究中,我们开发了一种新型的纳米工程微球制剂,其包含藻酸盐微球葡萄糖传感器和载有抗炎药物的藻酸盐微球。
制备该制剂并对其大小、形状、体外药物释放、生物相容性和体内可接受性进行表征。制备并表征了基于葡萄糖氧化酶(GOx)和脱辅基葡萄糖氧化酶(Apo-GOx)的葡萄糖传感器。在蒸馏水和模拟组织间液中进行传感。采用层层自组装技术防止药物和传感化学反应物释放。最后,使用Sprague-Dawley大鼠对植入传感器周围的皮下组织进行组织病理学检查,进行体内研究,以测试与葡萄糖传感器植入相关的炎症和纤维化的抑制情况。
该药物制剂在30天内显示100%药物释放,具有零级释放动力学。基于GOx的传感器在1个月内显示出良好的酶保留率和酶活性。基于Apo-GOx的可见光和近红外传感器显示出良好的灵敏度,分析响应范围为0-50 mM葡萄糖,线性范围高达12 mM葡萄糖浓度。体外细胞系研究证明了所用材料的生物相容性。最后,两种抗炎药物均成功地通过抑制植入部位的炎症来控制植入物与组织的界面。
将抗炎药物与葡萄糖生物传感器结合使用有望提高传感器的生物相容性,从而表明藻酸盐微球作为功能寿命更长的“智能纹身”葡萄糖传感器具有潜在应用价值。