Preparation and stability of poly(ethylene glycol) (PEG)ylated octreotide for application to microsphere delivery
AUTOR(ES)
Na, Dong Hee
FONTE
Springer-Verlag
RESUMO
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 reverse-phase high-performance liquid chromatography (HPLC) and characterized by matrixassisted 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°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°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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2750665Documentos Relacionados
- The different faces of poly(ethylene glycol)
- Preparation of thermostable poly(ethylene glycol) using thermal treatment in sealed system
- Poly(ethylene glycol) or Poly(ethylene oxide)?: Magnitude of end-group Contribution to the Partitioning of Ethylene Oxide Oligomers and Polymers between Water and Organic Phases
- Measurements of attractive forces between proteins and end-grafted poly(ethylene glycol) chains
- Effects of reaction conditions on the grafting percentage of poly(ethylene glycol)-block-poly(γ-benzyl L-glutamate)-graft-poly(ethylene glycol) copolymer