Selmani Atiđa, Seibert Elisabeth, Tetyczka Carolin, Kuehnelt Doris, Vidakovic Ivan, Kornmueller Karin, Absenger-Novak Markus, Radatović Borna, Vinković Vrček Ivana, Leitinger Gerd, Fröhlich Eleonore, Bernkop-Schnürch Andreas, Roblegg Eva, Prassl Ruth
Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmaceutical Sciences, University of Graz, 8010 Graz, Austria.
Division of Biophysics, Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, 8010 Graz, Austria.
Pharmaceutics. 2022 Apr 6;14(4):803. doi: 10.3390/pharmaceutics14040803.
This study aimed to design a hybrid oral liposomal delivery system for selenium nanoparticles (Lip-SeNPs) to improve the bioavailability of selenium. Thiolated chitosan, a multifunctional polymer with mucoadhesive properties, was used for surface functionalization of Lip-SeNPs. Selenium nanoparticle (SeNP)-loaded liposomes were manufactured by a single step microfluidics-assisted chemical reduction and assembling process. Subsequently, chitosan-N-acetylcysteine was covalently conjugated to the preformed Lip-SeNPs. The Lip-SeNPs were characterized in terms of composition, morphology, size, zeta potential, lipid organization, loading efficiency and radical scavenging activity. A co-culture system (Caco-2:HT29-MTX) that integrates mucus secreting and enterocyte-like cell types was used as a model of the human intestinal epithelium to determine adsorption, mucus penetration, release and transport properties of Lip-SeNPs in vitro. Thiolated Lip-SeNPs were positively charged with an average size of about 250 nm. Thiolated Lip-SeNPs tightly adhered to the mucus layer without penetrating the enterocytes. This finding was consistent with ex vivo adsorption studies using freshly excised porcine small intestinal tissues. Due to the improved mucoadhesion and retention in a simulated microenvironment of the small intestine, thiolated Lip-SeNPs might be a promising tool for oral selenium delivery.
本研究旨在设计一种用于硒纳米颗粒(Lip-SeNPs)的混合口服脂质体递送系统,以提高硒的生物利用度。硫醇化壳聚糖是一种具有粘膜粘附特性的多功能聚合物,用于Lip-SeNPs的表面功能化。通过单步微流控辅助化学还原和组装工艺制备了负载硒纳米颗粒(SeNP)的脂质体。随后,将壳聚糖-N-乙酰半胱氨酸共价偶联到预先形成的Lip-SeNPs上。对Lip-SeNPs的组成、形态、大小、zeta电位、脂质组织、负载效率和自由基清除活性进行了表征。使用整合了分泌粘液和肠上皮样细胞类型的共培养系统(Caco-2:HT29-MTX)作为人肠上皮模型,以确定Lip-SeNPs在体外的吸附、粘液渗透、释放和转运特性。硫醇化Lip-SeNPs带正电荷,平均大小约为250 nm。硫醇化Lip-SeNPs紧密粘附于粘液层,未穿透肠上皮细胞。这一发现与使用新鲜切除的猪小肠组织进行的体外吸附研究结果一致。由于在小肠模拟微环境中粘膜粘附性和滞留性得到改善,硫醇化Lip-SeNPs可能是一种有前途的口服硒递送工具。