Hydrophilic polymers for drug delivery

Synthesis and results of biological evaluation of two types of water-soluble polymer drug carrier systems designed for site-specific therapy are described. In the first system, a nondegradable poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) bears biodegradable oligopeptide side chains, terminated in the targeting antibody and/or anti-cancer drug doxorubicin, randomly distributed along the polymer chain. The other system is based on PEG (M-w 2000) blocks connected with biodegradable N-2,N-6-bis(glutamyl)-lysine oligopeptide links. This linear water-soluble polymer bears doxorubicin attached to the carboxylic groups of amino acid residues in the oligopeptide links via biodegradable GlyPheLeuGly spacer. Both systems release doxorubicin in vitro after incubation with lysosomal enzyme cathepsin B and exhibit in vivo anti-cancer activity in the treatment of selected model mice cancers. PHPMA, PEG and PHPMA-drug carriers, if conjugated with the antibody to form antibody-targeted systems, significantly decrease its immunogenicity (approx. by order of magnitude two).