Self-emulsifying drug delivery systems (SEDDS): Proof-of-concept how to make them mucoadhesive

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• 作者：Gintare Leonaviciute ; Nada Trivic Adamovic ; Hung Thanh Lam ; Julia Rohrer ; Alexandra Partenhauser ; Andreas Bernkop-Schnü ; rch ; ^{andreas.bernkop@uibk.ac.at}
• 关键词：Eudragit® ; S100 ; Cysteamine ; Mucoadhesion ; Self-emulsifying system ; Thiol group
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：112
• 期：Complete
• 页码：51-57
• 全文大小：603 K
• 卷排序：112

文摘

The objective of this study was to provide a proof-of-concept that self-emulsifying drug delivery systems can be made mucoadhesive by the incorporation of hydrophobic mucoadhesive polymers.MethodsIn order to obtain such a hydrophobic mucoadhesive polymer, Eudragit® S100 was thiolated by covalent attachment of cysteamine. After determination of the thiol group content, in vitro mucoadhesion studies (rotating cylinder and rheological measurements) were performed. Then, synthesized conjugate was incorporated into self-emulsifying drug delivery systems (SEDDS) and their toxic potential as well as that of unmodified and thiolated Eudragit® S100 was examined on Caco-2 cell line. Lastly, the mucoadhesiveness of developed SEDDS on porcine intestinal mucosa was determined.ResultsGenerated thiolated Eudragit® S100 displaying 235 ± 14 μmol of free thiol groups and 878 ± 101 μmol of disulfide bonds per gram polymer showed a great improvement in both: dynamic viscosity with mucus and adhesion time on mucosal tissue compared to the unmodified polymer. Resazurin assay revealed that unmodified and thiolated polymers and also SEDDS dispersions were non-toxic over Caco-2 cells. Furthermore, the incorporation of 1.5% (w/w) of such thiomer into SEDDS led to remarkably improved mucoadhesiveness. Blank SEDDS were completely removed from the mucosa within 15 min, whereas >60% of SEDDS containing thiolated Eudragit® S100 were still attached to it.ConclusionThese results provide evidence that SEDDS can be made mucoadhesive by the incorporation of hydrophobic mucoadhesive polymers.