Strategies for therapy of retinal diseases using systemic drug delivery: relevance of transporters at the blood-retinal barrier.
BACKGROUND
There is an increasing need for managing rapidly progressing retinal diseases because of the potential loss of vision. Although systemic drug administration is one possible route for treating retinal diseases, retinal transfer of therapeutic drugs from the circulating blood is strictly regulated by the blood-retinal barrier (BRB).


METHODS
This review discusses the constraints and challenges of drug delivery to the retina. In addition, this article discusses the properties of drugs and the conditions of the BRB that affect drug permeability. The reader will gain insights into the strategies for developing therapeutic drugs that are able to cross the BRB for treating retinal diseases. Further, the reader will gain insights into the role of BRB physiology including barrier functions, and the effect of influx and efflux transporters on retinal drug delivery.


CONCLUSIONS
When designing and selecting optimal drug candidates, it's important to consider the fact that they should be recognized by influx transporters and that efflux transporters at the BRB should be avoided. Although lipophilic cationic drugs are known to be transported to the brain across the blood-brain barrier, verapamil transport to the retina is substantially higher than to the brain. Therefore, lipophilic cationic drugs do have a great ability to increase influx transport across the BRB.
University of Toyama, Graduate School of Medicine and Pharmaceutical Sciences, Department of Pharmaceutics, 2630, Sugitani, Toyama 930 0194, Japan. hosoyak@pha.u-toyama.ac.jp
Ken-ichi
K
Hosoya
Masatoshi
M
Tomi
Masanori
M
Tachikawa
D000818:Animals; D001813:Blood-Retinal Barrier / Q000378:metabolism*; D004333:Drug Administration Routes; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D026901:Membrane Transport Proteins / Q000378:metabolism*; D010539:Permeability; D012164:Retinal Diseases / Q000188:drug therapy* / Q000378:metabolism
D026901:Membrane Transport Proteins