Sadeghi A M M, Avadi M R, Ejtemaimehr Sh, Abashzadeh Sh, Partoazar A, Dorkoosh F, Faghihi M, Rafiee-Tehrani M, Junginger H E
Division of Pharmaceutical Technology, Leiden University, P.O. Box 9502, 2300RA Leiden, The Netherlands.
J Control Release. 2009 Feb 20;134(1):11-7. doi: 10.1016/j.jconrel.2008.10.012. Epub 2008 Oct 26.
The aim of this investigation was to design a novel Gas Empowered Drug Delivery (GEDD) system for CO(2) forced transport of peptide drugs together with mucoadhesive polymers to the surface of the small intestine. The GEDD effect of the core tablet was achieved using CO(2) gas to push insulin together with the mucoadhesive excipients poly(ethyleneoxide) (PEO) and the permeation enhancer trimethyl chitosan (TMC) to the surface of the small intestine. The in-vitro insulin release showed that almost 100% of the insulin was released from enterically coated tablets within 30 min at pH 6.8. The designed GEDD system was shown to increase the insulin transport by approximately 7 times in comparison with the free insulin across sheep's intestine ex-vivo. Three different peroral formulations were administered to male rabbits: F1 containing no TMC or PEO, F2 containing PEO but no TMC and F3 containing both PEO and TMC. The administrations of insulin using the formulation F1 resulted in a low FR value of 0.2%+/-0.1%, while the formulations F2 and F3 resulted in a much higher FR values of 0.6+/-0.2% and 1.1%+/-0.4%, respectively. Hence, the insulin permeation achieved by the GEDD system is primarily due to the enhancing effect of TMC and the mucoadhesive properties of PEO both of which synergistically increase the bioavailability of insulin.
本研究的目的是设计一种新型气体驱动药物递送（GEDD）系统，用于将肽类药物与粘膜粘附聚合物一起通过二氧化碳强制运输至小肠表面。通过使用二氧化碳气体将胰岛素与粘膜粘附辅料聚环氧乙烷（PEO）和渗透促进剂三甲基壳聚糖（TMC）推至小肠表面，实现了核心片剂的GEDD效应。体外胰岛素释放表明，在pH 6.8条件下，肠溶包衣片在30分钟内几乎100%释放胰岛素。与游离胰岛素相比，所设计的GEDD系统在离体羊肠中使胰岛素转运增加了约7倍。将三种不同的口服制剂给予雄性兔子：F1不含TMC或PEO，F2含PEO但不含TMC，F3同时含PEO和TMC。使用制剂F1给药胰岛素导致低FR值为0.2%±0.1%，而制剂F2和F3的FR值分别高得多，为0.6±0.2%和1.1%±0.4%。因此，GEDD系统实现的胰岛素渗透主要归因于TMC的增强作用和PEO的粘膜粘附特性，二者协同提高了胰岛素的生物利用度。
