Park, Mi-Ran Chun, ChangJu Ahn, Sung-Won Ki, Min-Hyo Cho, Chong-Su Song, Soo-Chang 2024-01-20T20:01:18Z 2024-01-20T20:01:18Z 2021-09-02 2010-02 0142-9612 https://pubs.kist.re.kr/handle/201004/131745 Thermosensitive and cationic poly(organophosphazenes) were designed and synthesized for the sustained delivery of human growth hormone (hGH) charged negatively at the physiological conditions to enhance greatly patient convenience and to improve efficacy and stability. Protamine for a complex formation with hGH was chosen and conjugated to carboxylic acid-terminated poly(organophosphazenes) by a covalent amide linkage. The aqueous solution of the cationic polymer conjugates formed a gel at 37 degrees C regardless of hGH presence. When the conjugate solution was mixed with hGH solution, a complex was formed and free hGH could be released from the complex. In the in vitro and in vivo release studies of hGH/polymer-protamine conjugate, the initial burst release was suppressed and the release period was prolonged as the protamine amount was increased. In the PK and PD studies with cynomolgus monkeys, a single administration of hGH/cationic polymer conjugate induced the elevated plasma level of hGH until 5 days and also elevated plasma level of IGF-1 as a function of free hGH until 13 days. These results suggest that the injectable, thermosensitive, and cationic poly(organophosphazene)-protamine conjugate may hold a great potential as an effective carrier for sustained release of hGH with improved patient convenience. stability and efficacy. (C) 2009 Elsevier Ltd. All rights reserved. English ELSEVIER SCI LTD RELEASE FORMULATION PROTEIN DELIVERY MOLECULAR-WEIGHT IN-VIVO HYDROGELS STABILITY POLYPHOSPHAZENES COPOLYMERS FUSION Cationic and thermosensitive protamine conjugated gels for enhancing sustained human growth hormone delivery Article 10.1016/j.biomaterials.2009.10.022 1 BIOMATERIALS, v.31, no.6, pp.1349 - 1359 BIOMATERIALS 31 6 1349 1359 scie scopus 000273985100038 2-s2.0-72149088227 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article RELEASE FORMULATION PROTEIN DELIVERY MOLECULAR-WEIGHT IN-VIVO HYDROGELS STABILITY POLYPHOSPHAZENES COPOLYMERS FUSION Human growth hormone (hGH) Protamine Thermosensitive hydrogel Ionic interaction Sustained protein delivery Complexation