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Ternary nanocomposite carriers based on organic clay-lipid vesicles as an effective colon-targeted drug delivery system: preparation and in vitro/in vivo characterization

Authors
 Hyeon Young Kim  ;  Jae Hee Cheon  ;  Sang Hoon Lee  ;  Jeong Youn Min  ;  Seung-Yun Back  ;  Jae Geun Song  ;  Da Hye Kim  ;  Soo-Jeong Lim  ;  Hyo-Kyung Han 
Citation
 JOURNAL OF NANOBIOTECHNOLOGY, Vol.18(1) : 17, 2020 
Journal Title
 JOURNAL OF NANOBIOTECHNOLOGY 
Issue Date
2020
MeSH
Animals ; Anti-Inflammatory Agents/chemistry* ; Anti-Inflammatory Agents/pharmacokinetics ; Budesonide/chemistry* ; Budesonide/pharmacokinetics ; Caco-2 Cells ; Clay/chemistry* ; Colon/metabolism* ; Drug Liberation ; Humans ; Hydrogen-Ion Concentration ; Interleukin-6/metabolism ; Lipids/chemistry* ; Liposomes/chemistry* ; Male ; Mice ; Nanocomposites/chemistry* ; Polymethacrylic Acids/chemistry ; RAW 264.7 Cells ; Rats, Sprague-Dawley ; Solubility ; Surface Properties ; Tissue Distribution ; Tumor Necrosis Factor-alpha/metabolism
Keywords
Aminoclay ; Colon-targeted ; Inflammatory disease ; Liposome ; Nanocomposite ; pH-dependent
Abstract
This study aimed to develop a new colon-targeted drug delivery system via the preparation of ternary nanocomposite carriers based on organic polymer, aminoclay and lipid vesicles. Budesonide (Bud), an anti-inflammatory drug was chosen as a model drug and encapsulated into three different formulations: liposome (Bud-Lip), aminoclay-coated liposome (AC-Bud-Lip), and Eudragit® S100-aminoclay double coated liposome (EAC-Bud-Lip). The formation of the aminoclay-lipid vesicle nanocomposite was confirmed by energy dispersive X-ray spectrum, transmission electron microscopy, and Fourier-transform infrared spectroscopy. All formulations were produced with a high encapsulation efficiency in a narrow size distribution. Drug release from EAC-Bud-Lip was approximately 10% for 2-h incubation at pH 1.2, implying the minimal drug release in acidic gastric condition. At pH 7.4, EAC-Bud-Lip underwent significant size reduction and exhibited drug release profiles similar to that from AC-Bud-Lip, implying the pH-dependent removal of the outer coating layer. Compared to free Bud solution, EAC-Bud-Lip achieved a higher drug uptake in Caco-2 cells and exhibited a stronger inhibition of TNF-α and IL-6 secretion in LPS-stimulated Raw264.7 cells. Furthermore, a bio-distribution study in mice demonstrated that Eudragit® S100-aminoclay dual coating led to a higher colonic distribution with a longer residence time, which correlated well with the delayed systemic drug exposure in rats. Taken together, the present study suggests that the ternary nanocomposite carrier consisting of Eudragit® S100, aminoclay, and lipid vesicle might be useful as an effective colon-targeted drug delivery system.
Files in This Item:
T202000713.pdf Download
DOI
10.1186/s12951-020-0579-7
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Cheon, Jae Hee(천재희) ORCID logo https://orcid.org/0000-0002-2282-8904
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/175557
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