Kang Feirong, Singh Jagdish
Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, ND 58105, USA.
Int J Pharm. 2005 Nov 4;304(1-2):83-90. doi: 10.1016/j.ijpharm.2005.07.024. Epub 2005 Sep 21.
The purpose of this study was to develop single-dose insulin delivery system based on in situ forming gel to provide basal insulin level for a prolonged period. The in situ forming gel formulation was prepared by dissolving poly(d,l-lactic acid) (PLA) in hydrophobic (benzyl benzoate) and hydrophilic (benzyl alcohol) solvent mixtures. In vitro release was carried out in phosphate buffered saline (PBS) (pH 7.4) and the amount of released insulin was quantified by MicroBCA assay. In vivo biocompatibility study of in situ forming gel system was based on the histological evaluation of the tissue samples retrieved from injection sites at different time points. The tissue reaction was evaluated over 12 weeks. Throughout this period, all formulations showed normal inflammatory and foreign body reactions characterized by the presence of macrophages, fibroblasts and foreign body giant cells. Neither necrosis nor tissue damage could be identified. At the end of 12 weeks, no distinct histological differences were observed in comparison to the control tissue samples. The comparable results between blank and insulin-loaded in situ forming gel system indicated that the insulin itself did not induce additional inflammatory reactions. The results suggested that in situ forming gel system was biocompatible.
本研究的目的是开发基于原位形成凝胶的单剂量胰岛素递送系统，以长时间提供基础胰岛素水平。原位形成凝胶制剂是通过将聚（d，l-乳酸）（PLA）溶解在疏水（苯甲酸苄酯）和亲水（苯甲醇）溶剂混合物中制备的。在磷酸盐缓冲盐水（PBS）（pH 7.4）中进行体外释放，并通过MicroBCA测定法定量释放的胰岛素量。原位形成凝胶系统的体内生物相容性研究基于对不同时间点从注射部位取回的组织样本的组织学评估。在12周内评估组织反应。在此期间，所有制剂均表现出正常的炎症和异物反应，其特征为存在巨噬细胞、成纤维细胞和异物巨细胞。未发现坏死或组织损伤。在12周结束时，与对照组织样本相比，未观察到明显的组织学差异。空白和载胰岛素原位形成凝胶系统之间的可比结果表明，胰岛素本身不会引发额外的炎症反应。结果表明原位形成凝胶系统具有生物相容性。
