Abstract:
PURPOSE:Polyesters with hydrophilic domains, i.e., poly(D,L-lactic-co-glycolic-co-hydroxymethyl glycolic acid) (PLGHMGA) and a multiblock copolymer of poly(ε-caprolactone)-PEG-poly(ε-caprolactone) and poly(L-lactide) ((PC-PEG-PC)-(PL)) are expected to cause less acylation of encapsulated peptides than fully hydrophobic matrices. Our purpose is to assess the extent and sites of acylation of octreotide loaded in microspheres using tandem mass spectrometry analysis. METHODS:Octreotide loaded microspheres were prepared by a double emulsion solvent evaporation technique. Release profiles of octreotide from hydrophilic microspheres were compared with that of PLGA microspheres. To scrutinize the structural information and localize the actual modification site(s) of octreotide, liquid chromatography ion-trap mass spectrometry (LC-ITMS) was performed on the acylated adducts. RESULTS:Hydrophilic microspheres showed less acylated adducts in comparison with PLGA microspheres. LC-MS/MS showed that besides the N-terminus and primary amine of lysine, the primary hydroxyl of the end group of octreotide was also subjected to acylation. Nucleophilic attack of the peptide can also occur to the carbamate bond presented in (PC-PEG-PC)-(PL) since 1,4-butanediisocyanate was used as the chain extender. CONCLUSIONS:Hydrophilic polyesters are promising systems for controlled release of peptide because substantially less acylation occurs in microspheres based on these polymers. LC-ITMS provided detailed structural information of octreotide modifications via mass analysis of ion fragments.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Shirangi M,Hennink WE,Somsen GW,van Nostrum CFdoi
10.1007/s11095-015-1685-3subject
Has Abstractpub_date
2015-09-01 00:00:00pages
3044-54issue
9eissn
0724-8741issn
1573-904Xjournal_volume
32pub_type
杂志文章abstract:PURPOSE:The combination of morphine and gabapentin seems promising for the treatment of postoperative and neuropathic pain. Despite the well characterised pharmacodynamic interaction, little is known about possible pharmacokinetic interactions. The aim of this study was to evaluate whether co-administration of the two ...
journal_title:Pharmaceutical research
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doi:10.1007/s11095-016-1988-z
更新日期:2016-11-01 00:00:00
abstract:PURPOSE:Carboxylesterases are important in the detoxification of drugs, pesticides and other xenobiotics. This study was to evaluate a series of substrates and inhibitors for characterizing these enzymes. METHODS:A series of novel aliphatic esters and thioesters were used in spectral assays to monitor human, murine an...
journal_title:Pharmaceutical research
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更新日期:2014-01-01 00:00:00
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
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doi:10.1023/a:1016205520044
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doi:10.1023/a:1016292232513
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更新日期:2007-11-01 00:00:00
abstract::Fibers were spun by the downward configuration of the wet spinning technique. This configuration is capable of encapsulating nonspherical and/or coarse particles. We examined encapsulation of propranolol hydrochloride and the ability of the fibers to act as a sustained-release delivery system for propranolol hydrochlo...
journal_title:Pharmaceutical research
pub_type: 杂志文章
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journal_title:Pharmaceutical research
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doi:10.1023/a:1016284815501
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更新日期:2015-07-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016091915733
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journal_title:Pharmaceutical research
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更新日期:2002-07-01 00:00:00
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更新日期:2013-03-01 00:00:00
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更新日期:2016-10-01 00:00:00
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更新日期:2010-09-01 00:00:00
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更新日期:2020-08-13 00:00:00
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更新日期:2003-02-01 00:00:00
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更新日期:2017-01-01 00:00:00