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The biological efficiency and bioavailability of human growth hormone delivered using injectable, ionic, thermosensitive poly(organophosphazene)-polyethylenimine conjugate hydrogels

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Title: The biological efficiency and bioavailability of human growth hormone delivered using injectable, ionic, thermosensitive poly(organophosphazene)-polyethylenimine conjugate hydrogels
Authors: Seo, Bo-Bae1, Park, Mi-Ran2, Chun, ChangJu3, Lee, Jae-Yeol1, Song, Soo-Chang2 scsong@kist.re.kr
Source: Biomaterials. Nov2011, Vol. 32 Issue 32, p8271-8280. 10p.
Subjects: Human growth hormone, Bioavailability, Bioconjugates, Hydrogels, Biodegradation, Pharmacokinetics, Solution (Chemistry), Polyphosphazenes
Abstract: Abstract: We have endeavored to develop injectable, thermosensitive, biodegradable hydrogels that prolong human growth hormone (hGH) release, improving bioavailability through introducing balanced ionic interactions. Cationic poly(organophosphazene)-polyethylenimine (PEI, 1.8 kDa) conjugate hydrogels were synthesized as those hydrogels for sustained delivery of anionic hGH with proper ionic strength of association/dissociation. We have additionally prepared different chain lengths of α-amino-ω-methoxy-poly(ethylene glycol) (AMPEG550 and AMPEG750) for the synthesis of conjugates as a means to control hydrogel degradation rates. All Aqueous solutions of PEI-conjugates became hydrogels hydrolyzable in proportion to AMPEG molecular weight at body temperature; these PEI-conjugates complexed with hGH and extended hGH release in vitro. In pharmacokinetic studies of hGH behavior in SD rats, hydrogels of PEI-conjugate/hGH complexes could suppress the initial burst-phase, and extend the duration, of release, as well as increasing of area under the curve (AUC) compared to controls including hGH solution or non-ionic hydrogel. In a hypophysectomized rat model, the biological efficacy of hGH delivered from PEI-conjugate/hGH complex hydrogels was equivalent to that from daily administration over four days based on body weight gain and width of the tibial growth plate. These results suggest that ionic, thermosensitive, poly(organophosphazene)-PEI-conjugate hydrogel demonstrates potential as an injectable depot for sustained delivery of bioavailable hGH. [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
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PubType: Academic Journal
PubTypeId: academicJournal
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  Data: The biological efficiency and bioavailability of human growth hormone delivered using injectable, ionic, thermosensitive poly(organophosphazene)-polyethylenimine conjugate hydrogels
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  Data: <searchLink fieldCode="AR" term="%22Seo%2C+Bo-Bae%22">Seo, Bo-Bae</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Park%2C+Mi-Ran%22">Park, Mi-Ran</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Chun%2C+ChangJu%22">Chun, ChangJu</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Lee%2C+Jae-Yeol%22">Lee, Jae-Yeol</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Song%2C+Soo-Chang%22">Song, Soo-Chang</searchLink><relatesTo>2</relatesTo><i> scsong@kist.re.kr</i>
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  Data: <searchLink fieldCode="JN" term="%22Biomaterials%22">Biomaterials</searchLink>. Nov2011, Vol. 32 Issue 32, p8271-8280. 10p.
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  Data: <searchLink fieldCode="DE" term="%22Human+growth+hormone%22">Human growth hormone</searchLink><br /><searchLink fieldCode="DE" term="%22Bioavailability%22">Bioavailability</searchLink><br /><searchLink fieldCode="DE" term="%22Bioconjugates%22">Bioconjugates</searchLink><br /><searchLink fieldCode="DE" term="%22Hydrogels%22">Hydrogels</searchLink><br /><searchLink fieldCode="DE" term="%22Biodegradation%22">Biodegradation</searchLink><br /><searchLink fieldCode="DE" term="%22Pharmacokinetics%22">Pharmacokinetics</searchLink><br /><searchLink fieldCode="DE" term="%22Solution+%28Chemistry%29%22">Solution (Chemistry)</searchLink><br /><searchLink fieldCode="DE" term="%22Polyphosphazenes%22">Polyphosphazenes</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: Abstract: We have endeavored to develop injectable, thermosensitive, biodegradable hydrogels that prolong human growth hormone (hGH) release, improving bioavailability through introducing balanced ionic interactions. Cationic poly(organophosphazene)-polyethylenimine (PEI, 1.8 kDa) conjugate hydrogels were synthesized as those hydrogels for sustained delivery of anionic hGH with proper ionic strength of association/dissociation. We have additionally prepared different chain lengths of α-amino-ω-methoxy-poly(ethylene glycol) (AMPEG550 and AMPEG750) for the synthesis of conjugates as a means to control hydrogel degradation rates. All Aqueous solutions of PEI-conjugates became hydrogels hydrolyzable in proportion to AMPEG molecular weight at body temperature; these PEI-conjugates complexed with hGH and extended hGH release in vitro. In pharmacokinetic studies of hGH behavior in SD rats, hydrogels of PEI-conjugate/hGH complexes could suppress the initial burst-phase, and extend the duration, of release, as well as increasing of area under the curve (AUC) compared to controls including hGH solution or non-ionic hydrogel. In a hypophysectomized rat model, the biological efficacy of hGH delivered from PEI-conjugate/hGH complex hydrogels was equivalent to that from daily administration over four days based on body weight gain and width of the tibial growth plate. These results suggest that ionic, thermosensitive, poly(organophosphazene)-PEI-conjugate hydrogel demonstrates potential as an injectable depot for sustained delivery of bioavailable hGH. [Copyright &y& Elsevier]
– Name: AbstractSuppliedCopyright
  Label:
  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.2011.07.033
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        Text: English
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      – SubjectFull: Bioconjugates
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      – SubjectFull: Hydrogels
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      – SubjectFull: Pharmacokinetics
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      – SubjectFull: Solution (Chemistry)
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      – SubjectFull: Polyphosphazenes
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      – TitleFull: The biological efficiency and bioavailability of human growth hormone delivered using injectable, ionic, thermosensitive poly(organophosphazene)-polyethylenimine conjugate hydrogels
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              Text: Nov2011
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              Y: 2011
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