Modification of epithelial tight junction integrity to enhance transmucosal absorption.
Tight junctions (TJs) located between adjacent epithelial cells restrict the movement of solutes, ions, and even water. Restriction of macromolecules by TJ structures impedes one potential route of absorption for biopharmaceutical drugs, a route known as the paracellular pathway. It is anticipated that an improved understanding of TJ structure and cellular mechanisms that regulate its function will lead to successful strategies for improved transmucosal drug absorption through the paracellular pathway. Based upon clinical correlations between TJ dysfunction and several disease states, any approach to modify TJ integrity to enhance drug absorption in this way must be tempered by an appreciation of potential safety concerns that might develop through sustained or repeated TJ alterations. This review describes a current understanding of epithelial TJ organization and examines potential methods and implications for regulated modification of TJ function for the enhanced uptake of drugs without detrimental clinical outcomes.
Mrsny
Randall J
RJ
School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, Wales, UK CF10 3XF. mrsnyr@cardiff.ac.uk
D000595:Amino Acid Sequence; D000818:Animals; D004337:Drug Carriers; D004848:Epithelium / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000378:metabolism*; D019108:Tight Junctions
D004337:Drug Carriers