Lysosomotropic delivery

Figure 9 HPMA copol5nner conjugates designed (i) to deliver drug extracellularly when cleaved by an external trigger (e.g., azo linkers), (ii) to transfer drugs across a biological barrier (e,g., oral peptide vaccine delivery), (iii) for lysosomotropic delivery of anticancer conjugates, or (iv) to deliver macromolecular drugs into the c5d osol via the endosomotropic route.

Tumor cells will be resistant to polymer-drug conjugate therapy designed for lysosomotropic delivery if (i) endocytic... 

The aliphatic monomers and cross-linkers such as 30 were also used to examine the properties of the resulting particulates for lysosomotropic delivery [22]. Particulates derived from 30 and related aliphatic monomers displayed good biocompatibility and fast hydrolysis rates at acidic pH values. This aliphatic cross-linker undergoes degradation to generate acetone as the carbonyl-related degradation... 

DES) was incorporated within the polyacetal mainchain. The first pH-responsive polymeric (tert-DES) drug adequate for lysosomotropic delivery was achieved in this way (Duncan, 2003). These conjugates rapidly released DES at acidic pH (65% in 96 h at pH 5.5) but were stable at neutral environment (4% in 96 h at pH 7.4). 

The Linkage Between Drug and Carrier 289 Table 11.3. Peptide sequences that have been used as spacers in lysosomotropic drug delivery. 

DeDuve and co-workers first pointed out the potential value of the conversion of drugs into macromolecular species which could only penetrate cells by means of pinocytosis. They used the term lysosomotropic drugs to describe compounds which accumulate in the lysosomal compartment of the cell and subsequently exhibit pharmacological effects. Pinocytic uptake obviously displays several features which make it particularly amenable to utilization as a route for drug delivery. These characteristics are summarised below ... 

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