APPLICATIONS OF THE CACO-2 MODEL IN THE DESIGN AND DEVELOPMENT OF ORALLY-ACTIVE DRUGS - ELUCIDATION OF BIOCHEMICAL AND PHYSICAL BARRIERS POSED BY THE INTESTINAL EPITHELIUM
Lsl. Gan et Dr. Thakker, APPLICATIONS OF THE CACO-2 MODEL IN THE DESIGN AND DEVELOPMENT OF ORALLY-ACTIVE DRUGS - ELUCIDATION OF BIOCHEMICAL AND PHYSICAL BARRIERS POSED BY THE INTESTINAL EPITHELIUM, Advanced drug delivery reviews, 23(1-3), 1997, pp. 77-98
Oral administration is the most important and preferred route of admin
istration for small molecular weight conventional drugs. The overall b
ioavailability of an orally administered drug depends on many factors,
including the physicochemical properties of the drug as well as the m
orphological and biochemical state of the intestinal epithelium. Our u
nderstanding of the factors governing oral delivery of drug molecules
is far from complete. As a result, the approaches to solve the problem
s related to oral drug delivery are often empirical in nature. The mul
tifaceted nature of the problems associated with poor oral bioavailabi
lity of drug molecules requires a systematic and reductionist approach
to understand the underlying factors affecting the bioavailability an
d absorption of these molecules. Thus, use of appropriate in vitro mod
els is extremely useful in elucidating the role of various physical an
d biochemical barriers (such as metabolic enzymes, drug transporters,
and the multidrug resistance (MDR) P-glycoprotein) to drug absorption.
In this chapter, we have discussed the use of one such in vitro model
, i.e. the Caco-2 cells, in elucidating the roles of the physical and
biochemical barriers to drug absorption posed by the intestinal epithe
lium. By using specific examples, we have illustrated how this improve
d understanding about the barriers to drug absorption can be used for
the design and development of drug candidates with enhanced oral absor
ption.