Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria.
Small. 2024 Jul;20(27):e2307618. doi: 10.1002/smll.202307618. Epub 2024 Feb 2.
This study aims to compare the potential of Polyethylene glycol (PEG-free and PEG-based self-emulsifying drug delivery systems (SEDDS) for the oral administration of insulin glargine (IG). Hydrophobic ion pairs (HIPs) of IG are formed using various counterions. HIPs are assessed for log P and dissociation behavior. They are incorporated into SEDDS based on polyglycerol (PG) and zwitterionic surfactant (ZW) using response surface methodology and compared to conventional PEG-SEDDS in size, stability, and log D . Oral IG bioavailability in PG/ZW-SEDDS and PEG-SEDDS is evaluated in rats. Among the various counterions studied, IG-BIS (bis(isotridecyl)sulfosuccinate) HIPs demonstrated the highest log P and an improved dissociation profile. PG/ZW-SEDDS and PEG-SEDDS have similar ≈40 nm sizes and are stable over 24 h. Both formulations have log D > 4 in water and >2 in 50 mM phosphate buffer pH 6.8. PG/ZW-SEDDS yielded an oral bioavailability of 2.13 ± 0.66% for IG, while the employment of PEG-SEDDS resulted in an oral bioavailability of 1.15 ± 0.35%. This study highlights the prospective utilization of PEG-free SEDDS involving the concurrent application of PG and ZW surfactants, an alternative to conventional PEG surfactants, for improved oral therapeutic (poly) peptide delivery.
本研究旨在比较聚乙二醇（PEG）免费和基于 PEG 的自乳化药物传递系统（SEDDS）用于口服甘精胰岛素（IG）的潜力。IG 的疏水离子对（HIP）是使用各种抗衡离子形成的。评估 HIP 的 log P 和离解行为。它们被纳入基于聚甘油（PG）和两性离子表面活性剂（ZW）的 SEDDS 中，使用响应面法，并与常规 PEG-SEDDS 在大小、稳定性和 log D 方面进行比较。在大鼠中评估 PG/ZW-SEDDS 和 PEG-SEDDS 中的口服 IG 生物利用度。在研究的各种抗衡离子中，IG-BIS（双（异十三烷基）磺基琥珀酸酯）HIP 表现出最高的 log P 和改善的离解谱。PG/ZW-SEDDS 和 PEG-SEDDS 的粒径相似，约为 40nm，在 24 小时内稳定。两种制剂在水中的 log D > 4，在 50mM 磷酸盐缓冲液 pH 6.8 中的 log D > 2。PG/ZW-SEDDS 使 IG 的口服生物利用度达到 2.13 ± 0.66%，而使用 PEG-SEDDS 则使口服生物利用度达到 1.15 ± 0.35%。本研究强调了使用不含 PEG 的 SEDDS 的前景，该 SEDDS 涉及同时应用 PG 和 ZW 表面活性剂，作为常规 PEG 表面活性剂的替代物，以改善口服治疗（多）肽传递。
