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. 2003 Dec 31;4(4):E72.
doi: 10.1208/pt040472.

Preparation and stability of poly(ethylene glycol) (PEG)ylated octreotide for application to microsphere delivery

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Preparation and stability of poly(ethylene glycol) (PEG)ylated octreotide for application to microsphere delivery

Dong Hee Na et al. AAPS PharmSciTech. .

Abstract

The purpose of this study was to prepare poly(ethylene glycol) (PEG)ylated octreotide and investigate the stability against acylation by polyester polymers such as poly(lactic acid) and poly(lactic-co-glycolic acid). Octreotide was modified by reaction with monomethoxy PEG-propionaldehyde (molecular weight 5,000) in the presence of sodium cyanoborohydride. The mono-PEGylated fraction was isolated by reversed-phase high-performance liquid chromatography (HPLC) and characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Circular dichroism demonstrated no significant secondary structural differences between mono-PEGylated octreotide (mono-PEG-octreotide) and intact octreotide. As a test system for the stability study against acylation reaction, lactic acid (LA) solutions with various concentrations and pH values were prepared with water dilution and subsequent accelerated equilibration at 90 degrees C for 24 hours. Native octreotide was found to be acylated in all the diluted LA solutions with different concentrations (42.5%, 21.3%, and 8.5%, wt/wt) and pH values (2.25, 1.47, and 1.85, respectively). The remaining amounts of intact octreotide continuously decreased to 50% through 30 days of incubation at 37 degrees C. MALDI-TOF MS identified the octreotide to be acylated by LA units. However, acylation reaction of mono-PEG-octreotide in LA solutions was negligible, and the remaining amounts of intact one through 30 days of incubation in LA solutions were also comparable to the initial concentration. These data suggest that mono-PEG-octreotide may prevent the acylation reaction in degrading PLA microspheres and possibly serve as a new source for somatostatin microsphere formulation.

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References

    1. Van de Weert M, Hennink WE, Jiskoot W. Protein instability in poly(lactic-co-glycolic acid) microparticles. Pharm Res. 2000;17:1159–1167. doi: 10.1023/A:1026498209874. - DOI - PubMed
    1. Fu K, Klibanov AM, Langer R. Protein stability in controlled-release systems. Nat Biotechnol. 2000;18:24–25. doi: 10.1038/71875. - DOI - PubMed
    1. Zhu G, Mallery SR, Schwendeman SP. Stabilization of proteins encapsulated in injectable poly (lactide-co-glycolide) Nat Biotechnol. 2000;18:52–57. doi: 10.1038/71916. - DOI - PubMed
    1. Shao PG, Bailey LC. Stabilization of pH-induced degradation of porcine insulin in biodegradable polyester microspheres. Pharm Dev Technol. 1999;4:633–642. doi: 10.1081/PDT-100101402. - DOI - PubMed
    1. Rothen-Weinhold A, Oudry N, Schwach-Abdellaoui K, Frutiger-Hughes S, Hughes GJ, Jeannerat D, Burger U, Besseghir K, Gurny R. Formation of peptide impurities in polyester matrices during implant manufacturing. Eur J Pharm Biopharm. 2000;49:253–257. doi: 10.1016/S0939-6411(00)00066-7. - DOI - PubMed

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