Biocompatibility and immunocompatibility of water-soluble polymers based on HPMA

Water-soluble copolymers based on N-(2-hydroxypropyl)methacrylamide (HPMA) are investigated as potential carriers of anticancer drugs. For application of such compounds in therapeutic practice their immunogenicity must be checked and copolymers must be found having a structure which would not only be suitable for drug targeting, but would also induce the smallest possible defense reaction in recipient organism. Homopolymer poly(HPMA) with MW around 30kDa is not recognized as a foreign molecule as no defense reaction against it was recorded. The attachment of side oligopeptide sequences to the HPMA backbone bestows a certain degree of immunogenicity which depends on the composition of the oligopeptidic side chains, dose and route of application, MW and the genotype of immunized individual. HPMA copolymers not only fail to induce a significant immune response against them but they have similar capacity as PEG to dramatically reduce the antibody response against proteins bound to them as a targeting moiety or for the therapeutic purpose. Moreover, the treatment with HPMA-based polymeric drugs evokes in host organism systemic anti-cancer immunity involving both specific and non-specific defense mechanisms of cancer-bearing host.