Renal Delivery Using Macromolecular Carriers The Low-Molecular Weight Protein Approach

Interestingly, after intravenous administration of a radiolabelled folate conjugate ( -In-dium-diethylenetriaminepenta acid (DTPA)-folate) in the rat, the conjugate was rapidly excreted in the urine. Moreover, after intravenous administration to athymic mice with a human tumour cell implant, the radiotracer was not only taken up by the subcutaneous tumour but was also taken up by the kidneys in significant quantities [63], indicating substantial renal selectivity of the folate conjugate. In addition to the kidney, the liver also has a high concentration of the folate-receptor [64]. 

3 Renal Delivery Using Macromolecular Carriers The Low Molecular Weight Protein Approach 

Low molecular weight proteins (LMWP) are freely filtered proteins with a molecular weight of less than 30 000 Dalton and are considered to be suitable as renal-specific drug carriers. The concept is based on four principles  

Drugs that have primary amino groups available for conjugation, for instance dopamine and doxorubicin, can in principle be coupled to LMWPs via oligopeptides. In contrast to the carboxypeptidases, the aminopeptidases appear to possess a broader specificity. To allow the release of terminal amino group-containing drugs in the acid environment of the lysosomes without the requirement of enzymes, an acid-sensitive spacer can be used. 

Drugs coupled via a disulfide bond like, captopril, are rapidly released from the protein-spacer moiety of the conjugate, enzymatically by 3-lyase and/or non-enzymatically by thiol-disulfide exchange with endogenous thiols [68]. 

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