Development of a real-time analysis platform for the transport of drug molecules through a phospholipid bilayer = 인지질 이중막을 통한 약물 분자의 이동 실시간 분석 플랫폼 개발

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Because numerous drugs are administered through an oral route and mainly absorbed at the intestine for its ultimate desired effects, the prediction of drug permeability across an intestinal epithelial cell membrane has been a crucial issue in drug discovery. Thus, various in vitro permeability assays have been developed such as the Caco-2 assay, the parallel artificial membrane permeability assay (PAMPA), the phospholipid vesicle-based permeation assays (PVPA) and Permeapad®. However, due to the laborious and quite expensive process for cell culture in the Caco-2 assay and the uncertain microscopic membrane structures of the other assays, a simpler yet more accurate and versatile technique is still required. Here, we developed a new technique to measure the permeability of drug molecules across a planar freestanding lipid bilayer with a large area and a well-defined structure. The lipid bilayer was constructed within a conventional UV spectrometer cell, and the transport of drug molecules across the bilayer was recorded by UV absorbance over time. Permeability was then computed from the time-dependent diffusion equation. We measured the permeability for several exemplary drugs and compared these values with previously reported ones. We found that our assay has a much higher permeability compared to the other assays, and this higher permeability is related to the thickness of the lipid bilayer. Also we were able to measure the dynamic permeability upon the addition of a membrane-disrupting surfactant demonstrating that our technique has the capability to detect real-time changes in permeability across the lipid bilayer.
Advisors
Choi, Siyoungresearcher최시영researcher
Description
한국과학기술원 :생명화학공학과,
Publisher
한국과학기술원
Issue Date
2018
Identifier
325007
Language
eng
Description

학위논문(석사) - 한국과학기술원 : 생명화학공학과, 2018.2,[iii , 28 p. :]

Keywords

Lipid bilayer▼aartificial cell membrane▼amembrane permeability▼aUV spectroscopy▼areal-time analysis; 지질 이중막▼a인공 세포막▼a막 투과도▼a자외선 분광분석법▼a실시간 분석

URI
http://hdl.handle.net/10203/266399
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=733889&flag=dissertation
Appears in Collection
CBE-Theses_Master(석사논문)
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