SUSTAINED-RELEASE OF RECOMBINANT HUMAN GROWTH-HORMONE FROM DEXTRAN VIA HYDROLYSIS OF AN IMINE BOND

Dextran T40 was oxidized with periodate to form aldehyde groups to whi ch recombinant human growth hormone (rhGH) was attached. Complex forma tion involved the reversible formation of an imine conjugate and the e xtent of complex formation was proportional to the degree of oxidation of the dextran. The complex was characterized by a variety of techniq ues including SEC, SDS-PAGE and IEF. In vitro, the rate of release of rhGH from a rhGH-dextran complex was inversely proportional to the deg ree of oxidation of the dextran. The released protein was characterize d by peptide mapping, N-terminal sequencing, SEC and SDS-PAGE. Sustain ed release of rhGH was observed in vivo, based on the observation of s ignificant weight gain in a rat bioassay.