Monitoring of peptide acylation inside degrading PLGA microspheres by capillary electrophoresis and MALDI-TOF mass spectrometry

Na, Dong Hee; Youn, Yu Seok; Lee, Sang Deuk; Son, Miwon; Kim, Won-Bae; DeLuca, Patrick P.; Lee, Kang Choon

doi:10.1016/s0168-3659(03)00366-3

Cited by 77 publications

(51 citation statements)

References 19 publications

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“…[67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83] Only these two configurations are covered in this review, although, brief descriptions of the other three are given in the succeeding paragraphs.…”

Section: Ionization Methodsmentioning

confidence: 99%

Recent Developments in Capillary Electrophoresis–Mass Spectrometry of Proteins and Peptides

Monton

Terabe

2005

ANAL. SCI.

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Many researchers have invested considerable efforts toward improving capillary electrophoresis (CE)-mass spectrometry (MS) systems so they can be applied better to standard analyses. This review highlights the developments in CE-MS of proteins and peptides over the last five years. It includes the developments in interfaces, sample-enrichment techniques, microfabricated devices, and some applications, largely in capillary zone electrophoresis (CZE), capillary isoelectric focusing (CIEF) and capillary isotachophoresis formats.

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Section: Ionization Methodsmentioning

confidence: 99%

Recent Developments in Capillary Electrophoresis–Mass Spectrometry of Proteins and Peptides

Monton

Terabe

2005

ANAL. SCI.

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“…Among several instability issues of peptides in PLGA matrix, the formation of acylated peptide impurities has emerged as significant instability mechanism in PLGA formulations (5,6). The acylated peptides are formed as a result of acylation of peptide's amines with ester backbone of PLGA followed by release of peptides conjugated with lactic or glycolic acid units by polymer hydrolysis (7)(8)(9). Nucleophilic groups of peptides, such as the primary amino groups present in the N terminus and Lys residue, have been reported to be the major targets for peptide acylation (8).…”

Section: Introductionmentioning

confidence: 99%

“…The acylated peptides are formed as a result of acylation of peptide's amines with ester backbone of PLGA followed by release of peptides conjugated with lactic or glycolic acid units by polymer hydrolysis (7)(8)(9). Nucleophilic groups of peptides, such as the primary amino groups present in the N terminus and Lys residue, have been reported to be the major targets for peptide acylation (8). The peptide acylation in PLGA formulations may result in the incomplete release of the peptide from the matrix and can affect the biological activity, pharmacological effect, and toxicity of peptide drugs (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Reversible Blocking of Amino Groups of Octreotide for the Inhibition of Formation of Acylated Peptide Impurities in Poly(Lactide-co-Glycolide) Delivery Systems

et al. 2011

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Abstract. The purpose of this study was to develop a novel method to inhibit the formation of acylated peptide impurities in poly(D,L-lactide-co-glycolide) (PLGA) formulations by reversely blocking the amino groups of octreotide with maleic anhydride (MA). Two mono-MA conjugates with different modification sites (N terminus and Lys residue) and di-MA conjugate of octreotide were prepared and isolated by reversed-phase high-performance liquid chromatography (RP-HPLC). The polymer interaction of peptides and the formation of acylated peptides were monitored by RP-HPLC. The stability of MA-octreotide conjugates in PLGA films was studied in 0.1 M phosphate buffer (pH 7.4) at 37°C. The conjugation of MA to octreotide substantially inhibited the interaction of peptide with PLGA polymer and the subsequent formation of acylated peptide impurities. The MA-octreotides were successfully converted to intact octreotide as pH drops by PLGA hydrolysis. In PLGA films, MAoctreotide also showed complete inhibition of peptide acylation. In conclusion, MA conjugation provides a viable approach for stabilizing peptides in PLGA delivery systems.

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“…Salmon calcitonin (sCT), an endogenous polypeptide hormone composed of 32 amino acids (3,432 Da), the primary structure of sCT are shown in Fig. 1 (3).…”

Section: Introductionmentioning

confidence: 99%

Preparation and Characterization of Salmon Calcitonin–biotin Conjugates

et al. 2008

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Abstract. This study was performed to prepare and characterize the biotinylated Salmon calcitonin (sCT) for oral delivery and evaluate the hypocalcemic effect of biotinylated-sCTs in rats. Biotinylated sCTs was characterized by using high performance liquid chromatography (HPLC) and MALDITOF-MS. The effect of biotinylation on permeability across Caco-2 cell monolayers was examined. Their hypocalcemic effect was determined in rats. Mono-and di-bio-sCTs were separated by reverse phase HPLC. The molecular weights of mono-bio-sCT and di-bio-sCT were determined to be 3,660.5 and 3,900.2 Da, respectively. The permeability of biotinylated-sCTs across Caco-2 cell monolayers was observed with a significant enhancement compared with sCT. Intrajejunal (ij) administration of mono-bio-sCT and di-biosCT resulted in sustained reduction in serum calcium levels, with a maximum reduction (% max(d)) of 21.6% and 30% after 4 h and 6 h of application, respectively. The biotin conjugation of sCT may be a promising strategy for increasing the oral bioavailability of sCT and achieving sustained calcium-lowering effects.

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Monitoring of peptide acylation inside degrading PLGA microspheres by capillary electrophoresis and MALDI-TOF mass spectrometry

Cited by 77 publications

References 19 publications

Recent Developments in Capillary Electrophoresis–Mass Spectrometry of Proteins and Peptides

Recent Developments in Capillary Electrophoresis–Mass Spectrometry of Proteins and Peptides

Reversible Blocking of Amino Groups of Octreotide for the Inhibition of Formation of Acylated Peptide Impurities in Poly(Lactide-co-Glycolide) Delivery Systems

Preparation and Characterization of Salmon Calcitonin–biotin Conjugates

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