Authors: Dong Hee Na Kang Choon Lee Patrick P DeLuca
Publish Date: 2005/05/17
Volume: 22, Issue: 5, Pages: 743-749
Abstract
Octreotide was chemically modified by reaction with succinimidyl propionate monomethoxy PEG SPAmPEG molecular weight 2000 or succinimidyl butyraldehydemPEG ALDmPEG molecular weight 2000 and 5000 The structural conformation of PEGoctreotides was evaluated by circular dichroism CD the biological activity was assessed by measuring the decrease of serum insulinlike growth factorI levels in rats and a pharmacokinetic study was performed after subcutaneous administration in rats The stability against acylation was investigated with polydllactidecoglycolide PLGAALDmPEG was sitespecific in PEGylating octreotide at the Nterminus The monoPEGoctreotides prepared with ALDmPEG monoALDPEGoctreotide which alkyl bond preserves the amine’s positive charge showed complete preservation of biological activity whereas the PEGoctreotides prepared with SPAmPEG showed lower activity In the CD analysis the spectra of the monoALDPEGoctreotides were nearly superimposable with that of native octreotide The monoALDPEG5Koctreotide showed significantly improved pharmacokinetic properties compared with monoALDPEG2Koctreotide as well as native octreotide Both monoALDPEG2K and monoALDPEG5Koctreotides were stable against acylation by degrading PLGA
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