Synthesis and Characterization of HPMA Copolymer Conjugates

Many HPMA copolymer conjugates have been described. They contain drugs (Table 1), proteins, antibodies, and targeting ligands (Table 2). Although many subtle changes 

Biological and clinical studies have underlined the fundamental importance of the polymer-drug linker. When a conjugate is administered parenterally its stability in the circulation and ability to release drug at an appropriate rate on arrival in the target tissue is a principal determinant of therapeutic index. A variety of chemistries can be used to create pendant linkers (Fig. 5) (10). Lysosomally degradable peptides ensure site-specific intracellular activation, but many drug candidates do not have a convenient aliphatic -NH2 for this purpose. 

5-Fluoruracil has been linked to HPMA copolymer bearing peptide side-chains via a-glycine (88), and hydrolytically labile terminal ester bonds were used to prepare conjugates of paclitaxel and camptothecin (76,77,116). The endosomal/ 

Platinum ligand Thiocthcr Amide Azo Hydrazonc Ester 

Whichever linkage chemistry is used, an important feature to note is the clear influence of drug loading on conjugate conformation in solution. This in turn governs drug release rate. Solution conformation determines rates 

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