Targeting caveolae for vesicular drug transport.
Caveolae are morphologically evident as omega-shaped invaginations of the plasma membrane with a diameter of 50-100 nm. They may also exist in a variety of other forms including flattened domains indistinguishable from the plasma membrane itself. At least in some cell types caveolae undertake transport functions including that of the endocytic and transcytotic movement of macromolecules, and indeed microbes and microbial toxins. Opportunities exist for basic and applied investigators working within the pharmaceutical sciences to exploit caveolae membrane interactions with the aim to develop of novel cellular or transcellular drug delivery strategies. This overview article will provide: pertinent information on the biology of the caveolae membrane system; review the various caveolae isolation methods; highlight some of the literature evidence showing that caveolae are functional with regard to macromolecule transport; discuss the role that caveolae could fulfill in the pulmonary absorption of therapeutic proteins from alveolar airspace to capillary blood following inhalational drug delivery, and finally review some very recent work showing proof-of-principle that caveolae domains can be targeted in a tissue-specific manner with highly selective ligands.
Gumbleton
Mark
M
Pharmaceutical Cell Biology, Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3XF, UK. gunbleton@cardiff.ac.uk
Hollins
Andrew J
AJ
Omidi
Yadollah
Y
Campbell
Lee
L
Taylor
Glyn
G
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D021941:Caveolae / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D022161:Transport Vesicles / Q000187:drug effects / Q000378:metabolism*