Defymed S.A.S, Strasbourg, France.
IRCAD, Strasbourg, France.
J Control Release. 2020 Apr 10;320:431-441. doi: 10.1016/j.jconrel.2020.01.055. Epub 2020 Jan 31.
Intraperitoneal insulin delivery has higher benefits than subcutaneous insulin administration but has limitations, including obstruction of the catheter used in delivery devices. To overcome these limitations this study assessed safety and efficacy of an alternative approach involving a new delivery device, named ExOlin® allowing diffuse release of insulin in the extraperitoneal site. The aim of this study is to validate both safety and efficacy of insulin delivery in extraperitoneal using ExOlin® device. Safety of the ExOlin® device implantation in the extraperitoneal site was investigated over a 3-month period in Wistar rat and landrace swine models before comparing efficacy pharmacokinetics and hepatic first-pass metabolism of insulin after focal delivery using a catheter or diffuse release via ExOlin® device in extraperitoneal. Implantation in rat and swine models demonstrated good integration of the device, validating the safety of the extraperitoneal site. In diabetic rats, direct insulin administration at the extraperitoneal showed an efficacy comparable to intraperitoneal and statistically significantly higher than subcutaneous route as shown by 23% lower AUC calculated from glycaemia profile. Diffuse extraperitoneal delivery of insulin via ExOlin® device in diabetic rats exhibited better efficacy than the subcutaneous route with up to six-fold lower peripheral insulin and higher hepatic first-pass than with intraperitoneal injection. Similar results were confirmed in the swine model after injecting insulin lispro via the device at the extraperitoneal site. In conclusion, diffuse administration of insulin at the extraperitoneal site via ExOlin® device is a new promising approach to physiologically treating type 1 diabetes. It can therefore be considered as a promising alternative to intraperitoneal route.
腹腔内胰岛素输送比皮下胰岛素给药具有更高的益处，但也存在局限性，包括输送装置中导管的阻塞。为了克服这些局限性，本研究评估了一种新的输送装置 ExOlin®的安全性和有效性，该装置可使胰岛素在腹膜外部位弥散释放。本研究的目的是验证使用 ExOlin®装置在腹膜外部位输送胰岛素的安全性和有效性。在比较经导管聚焦输送或通过 ExOlin®装置在腹膜外部位弥散释放后，胰岛素的药代动力学和肝首过代谢的疗效之前，我们在 Wistar 大鼠和长白猪模型中对 ExOlin®装置在腹膜外部位的植入进行了为期 3 个月的安全性研究。在大鼠和猪模型中的植入表明，该装置具有良好的整合性，验证了腹膜外部位的安全性。在糖尿病大鼠中，直接在腹膜外给予胰岛素的疗效与腹腔内给药相当，且统计学上显著高于皮下给药，其 AUC 计算结果表明血糖谱降低了 23%。通过 ExOlin®装置在糖尿病大鼠中进行的胰岛素在腹膜外的弥散输送比皮下给药具有更好的疗效，外周胰岛素降低了多达 6 倍，肝首过效应更高。在经该装置向腹膜外部位注射胰岛素赖脯氨酸的猪模型中也得到了类似的结果。总之，通过 ExOlin®装置在腹膜外部位进行胰岛素的弥散给药是一种治疗 1 型糖尿病的有前途的新方法。因此，它可以被认为是一种有前途的腹腔内给药替代方法。
