Drug targeting to the kidney: Advances in the active targeting of therapeutics to proximal tubular cells.
Activated signaling cascades in the proximal tubular cells of the kidneys play a crucial role in the development of tubulointerstitial fibrosis. Inhibition of these signaling cascades with locally delivered therapeutics is an attractive approach to minimize the risk of unwanted side effects and to enhance their efficacy within the renal tissue. This review describes the potential avenues to actively target drugs to proximal tubular cells by recognition of internalizing receptors and how drug carriers can reach this cell type from either the apical or basolateral side. Important characteristics of drug carrier systems such as size and charge are discussed, as well as linking technologies that have been used for the coupling of drugs to the presented carrier systems. Lastly, we discuss the cellular handling of drugs by proximal tubular cells after their delivery to the kidneys.
Dolman
M E M
ME
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands. m.e.m.dolman@uu.nl
Harmsen
S
S
Storm
G
G
Hennink
W E
WE
Kok
R J
RJ
D004337:Drug Carriers; D016503:Drug Delivery Systems; D005355:Fibrosis; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*
D004337:Drug Carriers