Cyclodextrin-mediated enhancement of gastrointestinal drug delivery: unveiling mucoadhesive and mucopenetrating synergy.

IF 5.5 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Drug Delivery and Translational Research Pub Date : 2025-10-01 Epub Date: 2025-03-20 DOI:10.1007/s13346-025-01832-w

Soheil Haddadzadegan, Ahmad Saleh, Florina Veider, Patrick Knoll, Flavia Laffleur, Gergely Kali, Andreas Bernkop-Schnürch

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Abstract

This study evaluates the in vivo mucoadhesive properties of thiolated cyclodextrins (CDs) with varying S-protection using polyethylene glycol (PEG) of different chain lengths. Free thiol groups of thiolated β-CDs (CD-SH) were S-protected with 1 kDa and 2 kDa PEG bearing a terminal thiol group, leading to third-generation of thiolated CDs (CD-SS-PEG). The structure of these thiolated CDs was confirmed and characterized by FT-IR, 1 H NMR, and colorimetric assays. Thiolated and S-protected CDs were evaluated regarding viscosity, cellular uptake and, in vitro and in vivo mucoadhesion. The viscosity of CD-SH, CD-SS-PEG 1 kDa, and CD-SS-PEG 2 kDa mixtures with mucus increased 9-, 7-, and 5.5-fold, respectively, compared to unmodified CD within 3 h. Cellular uptake on Caco-2 cells was 1.75 times higher for highly thiolated CDs than for unmodified CD. In vitro residence time on porcine intestine was prolonged 7-, 8.4-, and 7.9-fold for CD-SH, CD-SS-PEG 1 kDa, and CD-SS-PEG 2 kDa, respectively. In vivo results indicated CD-SS-PEG 1 kDa had the highest potential. Our comprehensive in vitro, ex vivo, and in vivo ffindings demonstrate that CD-SS-PEG 1 kDa is a highly promising candidate for mucoadhesive drug delivery systems.

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环糊精介导的胃肠道药物传递增强：揭示黏附和黏液穿透协同作用。

本研究评估了巯基环糊精（CDs）在不同链长聚乙二醇（PEG）保护下的体内黏附性能。巯基化β- cd （CD-SH）的游离巯基被1 kDa和2 kDa的末端巯基的PEG s保护，从而形成第三代巯基化cd （CD-SS-PEG）。这些硫代CDs的结构被FT-IR、1h NMR和比色法证实和表征。评估硫代和s保护CDs的粘度、细胞摄取以及体外和体内黏附。在3小时内，CD- sh、CD- ss - peg 1 kDa和CD- ss - peg 2 kDa与黏液混合物的黏度分别比未修饰的CD增加了9倍、7倍和5.5倍。高硫化CD对cco -2细胞的吸收是未修饰CD的1.75倍。CD- sh、CD- ss - peg 1 kDa和CD- ss - peg 2 kDa的体外停留时间分别延长了7倍、8.4倍和7.9倍。体内实验结果显示CD-SS-PEG 1 kDa具有最高电位。我们在体外、离体和体内的综合研究结果表明，CD-SS-PEG 1 kDa是一种非常有前途的黏附给药系统候选者。

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来源期刊

Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY

CiteScore

11.70

自引率

1.90%

发文量

160

期刊介绍： The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.