The Linkage Between Drug and Carrier

Several other modifications have been explored for the targeted delivery of SOD. Chemical modification with hydrophilic monomethoxypolyethyleneglycol polymers (MPEG) resulted in a derivative with an increased molecular weight of 130 kDa, and hence a reduced renal elimination rate. The MPEG-SOD preparations reduced arthritic lesions in a complete adjuvant arthritis model in the rat, while native SOD did not show an anti-inflammatory effect [55]. 

Another antioxidative enzyme that has been targeted to the liver is catalase (CAT). Suc-cinylation and mannosylation resulted in an increased accumulation of the protein in the non-parenchymal cells of the liver. Furthermore, the CAT derivatives reduced hepatic injury in an ischaemia/reperfusion injury model [56]. 

Following cysteine residues, the second most reactive groups in a protein are the primary amino groups, avahable in both lysine residues and at the N-terminus of the protein backbone. Since primary amino groups are present in abundance in proteins, most conjugation re- 

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

Shen and Ryser developed daunorubicin-linked amino-ethyl polyacrylamide beads (Affi-gel 701) or poly(D-lysine) via an Af-cfr-aconityl spacer. The cis-aconityl linkage between drug and carrier was readily hydrolysed at pH 4 but not appreciably at pH 6. Poly(D-lysine) caused 90%... 

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