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Your search keyword '"Shirangi, Mehrnoosh"' showing total 3 results
Start Over Author "Shirangi, Mehrnoosh" Topic plga
3 results on '"Shirangi, Mehrnoosh"'

2. Acylation of arginine in goserelin-loaded PLGA microspheres

Author

Shirangi, Mehrnoosh, Hennink, Wim E., Somsen, Govert W., Van Nostrum, Cornelus F., Pharmaceutics, Sub General Pharmaceutics, Sub Drug delivery, Dep Farmaceutische wetenschappen, Pharmaceutics, Sub General Pharmaceutics, Sub Drug delivery, Dep Farmaceutische wetenschappen, AIMMS, and BioAnalytical Chemistry

Subjects
Arginine, Acylation, Lysine, Pharmaceutical Science, Peptide, 02 engineering and technology, 030226 pharmacology & pharmacy, Mass Spectrometry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Polylactic Acid-Polyglycolic Acid Copolymer, Taverne, Controlled release, Lactic Acid, Guanidine, Glycolic acid, chemistry.chemical_classification, Chromatography, PLGA, General Medicine, 021001 nanoscience & nanotechnology, Microspheres, LC-MS, chemistry, Goserelin, 0210 nano-technology, Peptides, SDG 6 - Clean Water and Sanitation, Polyglycolic Acid, Chromatography, Liquid, Biotechnology
Abstract

Acylation of peptides is a well-known but unwanted phenomenon in polyester matrices such as poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres used as controlled release formulations. Acylation normally occurs on lysine residues and the N-terminus of the peptide. The purpose of the present work was to assess other possible acylation sites on peptides. Goserelin was used as a model peptide that lacks lysine and a free N-terminus, but contains other nucleophilic residues, i.e. serine, tyrosine and arginine, which potentially can be acylated. Goserelin loaded PLGA microspheres were prepared by a double emulsion solvent evaporation technique. Liquid chromatography ion-trap mass spectrometry (LC-ITMS) was used for determining and monitoring acylation of released goserelin. It is demonstrated that arginine is subjected to acylation with glycolic acid and lactic acid units of PLGA, which was followed by loss of NH3 from the guanidine group to obtain 2-oxazolin-4-one and 5-methyl-2-oxazolin-4-one residues with masses that are 41 and 55 Da higher, respectively, than the native goserelin. There was no evidence for acylation of serine and tyrosine in goserelin. Our results demonstrate that beside lysine also acylation of arginine can occur in peptides and proteins that are loaded and released from PLGA matrixes.

Published
2016

3. Design of experiments approach for the development of a validated method to determine the exenatide content in poly(lactide-co-glycolide) microspheres.

Author

Sheikhi, Mojgan, Sharifzadeh, Mohammad, Hennink, Wim E., Firoozpour, Loghman, Hajimahmoodi, Mannan, Khoshayand, Mohammad Reza, and Shirangi, Mehrnoosh

Subjects
*MICROSPHERES, *EXENATIDE, *EXPERIMENTAL design, *PEPTIDE drugs, *FACTORIAL experiment designs
Abstract

[Display omitted] Due to the lack of pharmacopeia guidelines for injectable microspheres based on poly (D, L-lactide-co-glycolide) (PLGA), an internal method validation is a critical prerequisite for quality assurance. One of the essential issues of developing peptide-based drugs loaded PLGA microspheres is the precise determination of the amount of peptide drug entrapped in the microspheres. The aim of this study is the development and optimization of a method for measuring the drug content loading of PLGA microspheres using exenatide as a model peptide drug. Exenatide-loaded PLGA microspheres were prepared by a double emulsion solvent evaporation method. The extraction method to determine exenatide content in microspheres was optimized using Design of Experiments (DoE) approach. After the initial screening of six factors, using Fractional Factorial design (FFD), four of them, including type of organic solvent, buffer/organic solvent ratio (v/v), shaking time and pH, exhibited significant effects on the response, namely the exenatide loading, and a Box-Behnken design (BBD) was subsequently applied to obtain its optimum level. The optimum level for organic solvent volume, buffer/organic solvent ratio, shaking time, and pH were 4 ml, 1, 5.6 hrs, and pH 6, respectively. The exenatide content in microspheres under these conditions was 6.4 ± 0.0 (%w/w), whereas a value of 6.1% was predicted by the derived equation. This excellent agreement between the actual and the predicted value demonstrates that the fitted model can thus be used to determine the exenatide content. [ABSTRACT FROM AUTHOR]

Published
2023
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