School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, P. R. China.
Shandong Laboratory of Advanced Materials and Green Manufacturing, Yantai, China.
AAPS J. 2024 Sep 12;26(5):102. doi: 10.1208/s12248-024-00971-1.
Oral administration of peptide represents a promising delivery route, however, it is hindered by the harsh gastrointestinal environment, leading to low in vivo absorption. In this study, auto-adaptive protein corona-AT 1002-cationic liposomes (Pc-AT-CLs) are constructed with the characteristic of hydrophilic and electrically neutral surface properties for the encapsulation of liraglutide. BSA protein corona is used to coat AT-CLs reducing the adherence of mucus, and may fall off after penetrating the mucus layer. Transmucus transport experiment demonstrated that the mucus penetration amount of Pc-AT-CLs are 1.45 times that of AT-CLs. After penetrating the mucus layer, AT-CLs complete transmembrane transport by the dual action of AT and cationic surface properties. Transmembrane transport experiment demonstrated that the apparent permeability coefficient (P) of AT-CLs is 2.03 times that of CLs. In vivo tests demonstrated that Pc-AT-CLs exhibited a significant hypoglycemic effect and enhanced the relative bioavailability comparing to free liraglutide. Pc-AT-CLs protect liraglutide from degradation, facilitate its absorption, and ultimately improve its oral bioavailability.
口服肽类代表了一种很有前途的给药途径，然而，它受到胃肠道恶劣环境的阻碍，导致体内吸收低。在这项研究中，具有亲水和电中性表面特性的自适应蛋白冠-AT1002-阳离子脂质体（Pc-AT-CLs）被构建用于封装利拉鲁肽。BSA 蛋白冠被用来包裹 AT-CLs，减少了对粘液的黏附，并且在穿透粘液层后可能会脱落。粘液穿透实验表明，Pc-AT-CLs 的粘液穿透量是 AT-CLs 的 1.45 倍。穿透粘液层后，AT-CLs 通过 AT 和阳离子表面特性的双重作用完成跨膜转运。跨膜转运实验表明，AT-CLs 的表观渗透系数（P）是 CLs 的 2.03 倍。体内实验表明，Pc-AT-CLs 表现出显著的降血糖作用，并提高了与游离利拉鲁肽相比的相对生物利用度。Pc-AT-CLs 保护利拉鲁肽免受降解，促进其吸收，最终提高其口服生物利用度。
