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Cationic and thermosensitive protamine conjugated gels for enhancing sustained human growth hormone delivery

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Title: Cationic and thermosensitive protamine conjugated gels for enhancing sustained human growth hormone delivery
Authors: Park, Mi-Ran1,2, Chun, ChangJu1, Ahn, Sung-Won3, Ki, Min-Hyo3, Cho, Chong-Su2,4, Song, Soo-Chang1 scsong@kist.re.kr
Source: Biomaterials. Feb2010, Vol. 31 Issue 6, p1349-1359. 11p.
Subjects: Cations, Protamines, Human growth hormone, Drug delivery systems, Pharmaceutical gels, Drug design, Drug stability, Drug efficacy
Abstract: Abstract: 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°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. [Copyright &y& Elsevier]
Copyright of Biomaterials is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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DbLabel: Engineering Source
An: 47355272
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PubTypeId: academicJournal
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  Data: Cationic and thermosensitive protamine conjugated gels for enhancing sustained human growth hormone delivery
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  Data: <searchLink fieldCode="AR" term="%22Park%2C+Mi-Ran%22">Park, Mi-Ran</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Chun%2C+ChangJu%22">Chun, ChangJu</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Ahn%2C+Sung-Won%22">Ahn, Sung-Won</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Ki%2C+Min-Hyo%22">Ki, Min-Hyo</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Cho%2C+Chong-Su%22">Cho, Chong-Su</searchLink><relatesTo>2,4</relatesTo><br /><searchLink fieldCode="AR" term="%22Song%2C+Soo-Chang%22">Song, Soo-Chang</searchLink><relatesTo>1</relatesTo><i> scsong@kist.re.kr</i>
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  Data: <searchLink fieldCode="JN" term="%22Biomaterials%22">Biomaterials</searchLink>. Feb2010, Vol. 31 Issue 6, p1349-1359. 11p.
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  Data: <searchLink fieldCode="DE" term="%22Cations%22">Cations</searchLink><br /><searchLink fieldCode="DE" term="%22Protamines%22">Protamines</searchLink><br /><searchLink fieldCode="DE" term="%22Human+growth+hormone%22">Human growth hormone</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+delivery+systems%22">Drug delivery systems</searchLink><br /><searchLink fieldCode="DE" term="%22Pharmaceutical+gels%22">Pharmaceutical gels</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+design%22">Drug design</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+stability%22">Drug stability</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+efficacy%22">Drug efficacy</searchLink>
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  Data: Abstract: 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°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. [Copyright &y& Elsevier]
– Name: AbstractSuppliedCopyright
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  Group: Ab
  Data: <i>Copyright of Biomaterials is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1016/j.biomaterials.2009.10.022
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        Text: English
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      – SubjectFull: Human growth hormone
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      – SubjectFull: Drug design
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      – SubjectFull: Drug stability
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      – SubjectFull: Drug efficacy
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      – TitleFull: Cationic and thermosensitive protamine conjugated gels for enhancing sustained human growth hormone delivery
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            NameFull: Park, Mi-Ran
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              Text: Feb2010
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