Drug Targeting Organ-Specific Strategies

via reabsorption from the luminal site. Lysosomal delivery allows drug attachment via an
acid-sensitive spacer or via biodegradable peptide or ester moieties. Using the alkylglycoside
vector as a drug carrier, the drug is taken up via the basolateral site into the proximal tubular
cell. It is as yet unknown to which compartment of the proximal tubular cell the drug is
delivered using this carrier, and the subsequent stages such as drug release as well as the kinetics
and dynamics during renal diseases remain to be studied. Yet, a basolateral delivery
may be advantageous during severe reduction of glomerular filtration and presence of proteinuria.
On the other hand, with low-molecular weight proteins a broader range of drugs
(with respect to their physicochemical properties) can be delivered to the proximal tubular
cells.
Oligonucleotide targeting to the kidney is more feasible than to many other tissues as a result
of the glomerular filtration and tubular reabsorption of these poly-anionic agents.The effect
is temporary allowing the therapy to be terminated when desired. Up until now, data has
only been available on the kinetics and some renal and extra-renal effects of oligonucleotides
in healthy animals.
The most relevant studies examining the effects of drug targeting in experimental disease,
are yet to come.These studies may provide clues to the role of the proximal tubular cell in the
various renal diseases and may determine whether treatment of renal disease can be accomplished
by drug targeting to the proximal tubular cell. A further goal of renal targeting is the
specific delivery of drugs to the filtration unit of the kidney, the glomerulus, which is also believed
to play an important role in the progression of renal disease. Until recently only limited
research has been focused on this target in the kidney [76].
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