A new class of inhibitors of peptide sorption and acylation in PLGA

JOURNAL OF CONTROLLED RELEASE

卷:137

Article

Sophocleous, Andreas M.^1,2  Zhang, Ying¹  Schwendeman, Steven P.¹ 

[1] Univ Michigan, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Dept Chem Sci, Ann Arbor, MI 48109 USA

关键词: Acylation;    Octreotide acetate;    Sorption;    Divalent cations;    PLGA;   

DOI  :  10.1016/j.jconrel.2009.03.006

来源: Elsevier

【 摘 要 】

Acylation of peptides occurring within controlled-release depots prepared from copolymers of lactic and glycolic acid (PLGA) is a degradation reaction that may compromise product safety and efficacy. As peptide sorption to PLGA is believed to be a common precursor to peptide acylation, a new method to inhibit acylation is presented involving disruptors of peptide sorption, namely, inorganic divalent cations. Kinetics of sorption of a model peptide, octreotide acetate, to free-acid end-group PLGA was monitored in the presence and absence of water-soluble inorganic divalent cationic salts in HEPES buffer solution (pH 74, 37 degrees C). Sorption of cations and octreotide attained pseudo-equilibrium by 24 h. From 24-h sorption isotherms, all cations studied inhibited octreotide sorption to PLGA-the inhibiting effect of the cations increased in the order: Na+

【 授权许可】

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