Journal
ADVANCED DRUG DELIVERY REVIEWS
Volume 54, Issue 4, Pages 505-530Publisher
ELSEVIER
DOI: 10.1016/S0169-409X(02)00025-X
Keywords
diabetes; poly(ethylene glycol); PEG-protein conjugates; protein delivery; pharmacokinetics; immunogenicity; protein stabilization; parenteral delivery
Categories
Funding
- NIDDK NIH HHS [DK-50557] Funding Source: Medline
Ask authors/readers for more resources
The goal of this research was to determine whether the site-specific attachment of poly(ethylene glycol) to insulin could enhance the physical and pharmacological properties of insulin without negatively affecting its biological activity or immunological properties. Electrophilically activated derivatives of low-molecular-weight monomethoxypoly(ethyleglycol) (mPEG) were chemically coupled to insulin via its amino groups at positions phenylalanine an amide bond being formed between the polymer and protein. The site-specific attachment of mPEG to insulin did not substantially alter insulin's secondary/ tertiary structure, self-association behavior, or potency in vivo. However, mPEG attachment did significantly enhance insulin's resistance to aggregation. In addition, the pegylation of insulin almost completely eliminates the resultant conjugate's immunogenicity, allergenicity, and antigenicity. Finally, the conjugates were observed to remain in the systemic circulation for longer periods of time than unmodified insulin after subcutaneous administration. (C) 2002 Elsevier Science B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available