Shenoy Dinesh B, D'Souza Reshma J, Tiwari Sandip B, Udupa N
Dr. T. M. A. Pai Pharmaceutical Research Centre, College of Pharmaceutical Sciences, Manipal, Karnataka, India.
Drug Dev Ind Pharm. 2003 May;29(5):555-63. doi: 10.1081/ddc-120018644.
The objective of this investigation was to develop an injectable, depot-forming drug delivery system for insulin based on microparticle technology to maintain constant plasma drug concentrations over prolonged period of time for the effective control blood sugar levels. Formulations were optimized with two well-characterized biodegradable polymers namely, poly(DL-lactide-co-glycolide) and poly-epsilon-caprolactone and evaluated in vitro for physicochemical characteristics, drug release in phosphate buffered saline (pH 7.4), and evaluated in vivo in streptozotocin-induced hypoglycemic rats. With a large volume of internal aqueous phase during w/o/w double emulsion solvent evaporation process and high molecular weight of the polymers used, we could not achieve high drug capture and precise control over subsequent release within the study period of 60 days. However, this investigation revealed that upon subcutaneous injection, the biodegradable depot-forming polymeric microspheres controlled the drug release and plasma sugar levels more efficiently than plain insulin injection. Preliminary pharmacokinetic evaluation exhibited steady plasma insulin concentration during the study period. These formulations, with their reduced frequency of administration and better control over drug disposition, may provide an economic benefit to the user compared with products currently available for diabetes control.
本研究的目的是基于微粒技术开发一种用于胰岛素的可注射长效药物递送系统，以在较长时间内维持恒定的血浆药物浓度，从而有效控制血糖水平。使用两种特性明确的可生物降解聚合物，即聚（DL-丙交酯-共-乙交酯）和聚-ε-己内酯对制剂进行优化，并在体外评估其物理化学特性、在磷酸盐缓冲盐水（pH 7.4）中的药物释放情况，并在链脲佐菌素诱导的低血糖大鼠体内进行评估。在w/o/w复乳溶剂蒸发过程中，由于内水相体积较大且所用聚合物分子量较高，在60天的研究期内，我们未能实现高药物捕获率以及对后续释放的精确控制。然而，本研究表明，皮下注射后，可生物降解的长效聚合物微球比普通胰岛素注射更有效地控制药物释放和血糖水平。初步药代动力学评估显示，在研究期间血浆胰岛素浓度稳定。与目前用于糖尿病控制的产品相比，这些制剂给药频率降低且对药物处置的控制更好，可能为使用者带来经济效益。
