Burshtein Gregory, Itin Constantin, Tang Jonathan C Y, Galitzer Hillel, Fraser William D, Schwartz Phillip
Entera Bio Ltd., Jerusalem BioPark, Jerusalem 9112002, Israel.
Bioanalytical Facility, Biomedical Research Centre, Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK.
Int J Pharm X. 2021 Oct 8;3:100097. doi: 10.1016/j.ijpx.2021.100097. eCollection 2021 Dec.
Oral delivery of peptides and proteins is hindered by their rapid proteolysis in the gastrointestinal tract and their inability to permeate biological membranes. Various drug delivery approaches are being investigated and implemented to overcome these obstacles. In the discussed study conducted in pigs, an investigation was undertaken to assess the effect of combination of a permeation enhancer - salcaprozate sodium, and a proteolysis inhibitor - soybean trypsin inhibitor, on the systemic exposure of the peptide teriparatide, following intraduodenal administration. Results demonstrate that this combination achieves significantly higher Cmax and AUC (~10- and ~20-fold respectively) compared to each of these methodologies on their own. It was thus concluded that an appropriate combination of different technological approaches may considerably contribute to an efficient oral delivery of biological macromolecules.
肽和蛋白质的口服给药受到它们在胃肠道中快速蛋白水解以及无法穿透生物膜的阻碍。正在研究和实施各种药物递送方法以克服这些障碍。在对猪进行的上述研究中，开展了一项调查，以评估渗透促进剂——沙卡丙酯钠和蛋白水解抑制剂——大豆胰蛋白酶抑制剂联合使用对十二指肠内给药后肽类药物特立帕肽全身暴露的影响。结果表明，与单独使用这些方法相比，这种联合使用使Cmax和AUC显著更高（分别约为10倍和20倍）。因此得出结论，不同技术方法的适当组合可能对生物大分子的有效口服给药有很大贡献。
