Drug lysosomal release

The drug-LMWP conjugate is stable in the circulation but after arrival in the kidney, the active drug is released in the catabolically-active lysosomes of the proximal tubular cells (Figure 5.7). 

Laakso, T., Stjarnkvist, R, Sjoholm, 1. (1987). Biodegradable microspheres VI Lysosomal release of covalently bound antiparasitic drugs from starch microparticles. J. Pharm. Sci., 76( ), 134-140. 

Oligopeptide sequences can be incorporated into N-(2-hydroxypropyl)methacryl-amide copolymers (for the different methods used see section 2) which serve as potential drug attachment/release sites and experiments have been carried out to investigate whether such sequences could be efficiently cleaved by lysosomal enzymes. 

After interaction of the aforementioned carriers with specific receptors, the carrier is then taken up by endocytosis and transported intracellularly to acidified endosomes and lyso-somes.The carrier is proteolytically degraded in the lysosomes and if a drug is coupled to the carrier, it is then released to diffuse into the cytoplasmic compartment. 

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. 

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