Controlled Release of Octreotide and Assessment of Peptide Acylation from Poly(D,L-lactide-co-hydroxymethyl glycolide) Compared to PLGA Microspheres
Identifieur interne : 000107 ( Ncbi/Checkpoint ); précédent : 000106; suivant : 000108Controlled Release of Octreotide and Assessment of Peptide Acylation from Poly(D,L-lactide-co-hydroxymethyl glycolide) Compared to PLGA Microspheres
Auteurs : Amir H. Ghassemi [Pays-Bas] ; Mies J. Van Steenbergen [Pays-Bas] ; Arjan Barendregt [Pays-Bas] ; Herre Talsma [Pays-Bas] ; Robbert J. Kok [Pays-Bas] ; Cornelus F. Van Nostrum [Pays-Bas] ; Daan J. A. Crommelin [Pays-Bas] ; Wim E. Hennink [Pays-Bas]Source :
- Pharmaceutical Research [ 0724-8741 ] ; 2011.
Abstract
To investigate the
Spherical and non-porous octreotide-loaded PLHMGA microspheres (12 to 16 μm) and loading efficiency of 60–70% were prepared by a solvent evaporation. Octreotide release profiles were compared with commercial PLGA formulation (Sandostatin LAR®); possible peptide modification with lactic, glycolic and hydroxymethyl glycolic acid units was monitored.
PLHMGA microspheres showed burst release (~20%) followed by sustained release for 20–60 days, depending on the hydrophilicity of the polymer. Percentage of released loaded peptide was high (70–90%); > 60% of released peptide was native octreotide. PLGA microspheres did not show peptide release for the first 10 days, after which it was released in a sustained manner over the next 90 days; > 75% of released peptides were acylated adducts.
PLHMGA microspheres are promising controlled systems for peptides with excellent control over release kinetics. Moreover, substantially less peptide modification occurred in PLHMGA than in PLGA microspheres.
The online version of this article (doi:10.1007/s11095-011-0517-3) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1007/s11095-011-0517-3
PubMed: 21744173
PubMed Central: 3246586
Affiliations:
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<country xml:lang="fr">Pays-Bas</country>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Controlled Release of Octreotide and Assessment of Peptide Acylation from Poly(D,L-lactide-co-hydroxymethyl glycolide) Compared to PLGA Microspheres</title>
<author><name sortKey="Ghassemi, Amir H" sort="Ghassemi, Amir H" uniqKey="Ghassemi A" first="Amir H." last="Ghassemi">Amir H. Ghassemi</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB Utrecht</wicri:regionArea>
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<placeName><settlement type="city">Utrecht</settlement>
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<author><name sortKey="Van Steenbergen, Mies J" sort="Van Steenbergen, Mies J" uniqKey="Van Steenbergen M" first="Mies J." last="Van Steenbergen">Mies J. Van Steenbergen</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB Utrecht</wicri:regionArea>
<orgName type="university">Université d'Utrecht</orgName>
<placeName><settlement type="city">Utrecht</settlement>
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<author><name sortKey="Barendregt, Arjan" sort="Barendregt, Arjan" uniqKey="Barendregt A" first="Arjan" last="Barendregt">Arjan Barendregt</name>
<affiliation wicri:level="4"><nlm:aff id="Aff2">Biomolecular Mass Spectrometry and Proteomics Group Bijvoet Center for Biomolecular Research Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Biomolecular Mass Spectrometry and Proteomics Group Bijvoet Center for Biomolecular Research Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht</wicri:regionArea>
<orgName type="university">Université d'Utrecht</orgName>
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<author><name sortKey="Talsma, Herre" sort="Talsma, Herre" uniqKey="Talsma H" first="Herre" last="Talsma">Herre Talsma</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB Utrecht</wicri:regionArea>
<orgName type="university">Université d'Utrecht</orgName>
<placeName><settlement type="city">Utrecht</settlement>
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<author><name sortKey="Kok, Robbert J" sort="Kok, Robbert J" uniqKey="Kok R" first="Robbert J." last="Kok">Robbert J. Kok</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB Utrecht</wicri:regionArea>
<orgName type="university">Université d'Utrecht</orgName>
<placeName><settlement type="city">Utrecht</settlement>
<region nuts="2">Utrecht (province)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Van Nostrum, Cornelus F" sort="Van Nostrum, Cornelus F" uniqKey="Van Nostrum C" first="Cornelus F." last="Van Nostrum">Cornelus F. Van Nostrum</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB Utrecht</wicri:regionArea>
<orgName type="university">Université d'Utrecht</orgName>
<placeName><settlement type="city">Utrecht</settlement>
<region nuts="2">Utrecht (province)</region>
</placeName>
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<author><name sortKey="Crommelin, Daan J A" sort="Crommelin, Daan J A" uniqKey="Crommelin D" first="Daan J. A." last="Crommelin">Daan J. A. Crommelin</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB Utrecht</wicri:regionArea>
<orgName type="university">Université d'Utrecht</orgName>
<placeName><settlement type="city">Utrecht</settlement>
<region nuts="2">Utrecht (province)</region>
</placeName>
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</author>
<author><name sortKey="Hennink, Wim E" sort="Hennink, Wim E" uniqKey="Hennink W" first="Wim E." last="Hennink">Wim E. Hennink</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB Utrecht</wicri:regionArea>
<orgName type="university">Université d'Utrecht</orgName>
<placeName><settlement type="city">Utrecht</settlement>
<region nuts="2">Utrecht (province)</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="Aff3">Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, 3584 CG Utrecht</wicri:regionArea>
<orgName type="university">Université d'Utrecht</orgName>
<placeName><settlement type="city">Utrecht</settlement>
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<series><title level="j">Pharmaceutical Research</title>
<idno type="ISSN">0724-8741</idno>
<idno type="eISSN">1573-904X</idno>
<imprint><date when="2011">2011</date>
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<front><div type="abstract" xml:lang="en"><title>ABSTRACT</title>
<sec><title>Purpose</title>
<p>To investigate the <italic>in vitro</italic>
release of octreotide acetate, a somatostatin agonist, from microspheres based on a hydrophilic polyester, poly(D,L-lactide-co-hydroxymethyl glycolide) (PLHMGA).</p>
</sec>
<sec><title>Methods</title>
<p>Spherical and non-porous octreotide-loaded PLHMGA microspheres (12 to 16 μm) and loading efficiency of 60–70% were prepared by a solvent evaporation. Octreotide release profiles were compared with commercial PLGA formulation (Sandostatin LAR<sup>®</sup>
); possible peptide modification with lactic, glycolic and hydroxymethyl glycolic acid units was monitored.</p>
</sec>
<sec><title>Results</title>
<p>PLHMGA microspheres showed burst release (~20%) followed by sustained release for 20–60 days, depending on the hydrophilicity of the polymer. Percentage of released loaded peptide was high (70–90%); > 60% of released peptide was native octreotide. PLGA microspheres did not show peptide release for the first 10 days, after which it was released in a sustained manner over the next 90 days; > 75% of released peptides were acylated adducts.</p>
</sec>
<sec><title>Conclusions</title>
<p>PLHMGA microspheres are promising controlled systems for peptides with excellent control over release kinetics. Moreover, substantially less peptide modification occurred in PLHMGA than in PLGA microspheres.</p>
</sec>
<sec><title>Electronic Supplementary Material</title>
<p>The online version of this article (doi:10.1007/s11095-011-0517-3) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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