Department of Pharmaceutical Technology, University of Innsbruck, Institute of Pharmacy, Center for Chemistry and Biomedicine, 6020 Innsbruck, Austria; Thiomatrix Forschungs- und Beratungs GmbH, Trientlgasse 65, 6020 Innsbruck, Austria.
Thiomatrix Forschungs- und Beratungs GmbH, Trientlgasse 65, 6020 Innsbruck, Austria.
Int J Pharm. 2023 May 25;639:122964. doi: 10.1016/j.ijpharm.2023.122964. Epub 2023 Apr 24.
In spite of recent progress made in the field of peptide and protein delivery, oral administration of insulin and similar drugs remains a challenge. In this study, lipophilicity of insulin glargine (IG) was successfully increased via hydrophobic ion pairing (HIP) with sodium octadecyl sulfate to enable incorporation into self-emulsifying drug delivery systems (SEDDS). Two SEDDS formulations (F1: 20% Labrasol®ALF, 30% polysorbate 80, 10% Croduret 50, 20% oleyl alcohol, 20% Maisine® CC; F2: 30% Labrasol®ALF, 20% polysorbate 80, 30% Kolliphor® HS 15, 20% Plurol® oleique CC 497) were developed and loaded with the IG-HIP complex. Further experiments confirmed increased lipophilicity of the complex, achieving LogD values of 2.5 (F1) and 2.4 (F2) and ensuring sufficient amounts of IG within the droplets after dilution. Toxicological assays indicated minor toxicity and no toxicity inherent to the incorporated IG-HIP complex. SEDDS formulations F1 and F2 were administered to rats via oral gavage and resulted in a bioavailability of 0.55% and 0.44%, corresponding to a 7.7-fold and 6.2-fold increased bioavailability, respectively. Thus, incorporation of complexed insulin glargine into SEDDS formulations provides a promising approach to facilitate its oral absorption.
尽管在肽和蛋白质递药领域取得了近期进展，但胰岛素和类似药物的口服给药仍然是一个挑战。在这项研究中，通过与十八烷基硫酸钠的疏水离子配对（HIP）成功增加了甘精胰岛素（IG）的亲脂性，从而能够将其纳入自乳化药物递送系统（SEDDS）中。开发了两种 SEDDS 配方（F1：20%Labrasol®ALF、30%聚山梨酯 80、10%Croduret 50、20%油醇、20%Maisine®CC；F2：30%Labrasol®ALF、20%聚山梨酯 80、30%Kolliphor®HS 15、20%Plurol®oleique CC 497），并加载了 IG-HIP 复合物。进一步的实验证实了该复合物的亲脂性增加，达到了 2.5（F1）和 2.4（F2）的 LogD 值，并确保了在稀释后滴内有足够量的 IG。毒理学试验表明，该复合物的毒性较小，且没有固有毒性。SEDDS 配方 F1 和 F2 通过口服灌胃给予大鼠，生物利用度分别为 0.55%和 0.44%，分别对应于 7.7 倍和 6.2 倍的生物利用度增加。因此，将复合胰岛素甘精胰岛素纳入 SEDDS 配方中为促进其口服吸收提供了一种有前途的方法。
