In vitro enzymatic stability of dendritic peptides

PEGylated polyamidoamine (PAMAM) dendrimers as drug carriers have been a topic of interest because of their biomedically favorable features, including minimal toxicity, reduced immunogenicity, and excellent solubility in aqueous and most organic solutions. A PEG shell on dendrimer surface may provid...

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Bibliographic Details
Published in:Journal of biomedical materials research. Part A 2006-02, Vol.76A (2), p.398-407
Main Authors: Yang, Hu, Lopina, Stephanie T.
Format: Article
Language:English
Subjects:
Biocompatible Materials - chemistry
Biocompatible Materials - metabolism
Chymotrypsin - metabolism
Dendrimers - chemistry
Dendrimers - metabolism
Drug Carriers - chemistry
Drug Carriers - metabolism
enzyme activity inhibition
Hydrolysis
Magnetic Resonance Spectroscopy
Michaelis-Menten equation
nanomedicine
PEG-PAMAM star polymer
peptide delivery
Peptides - chemistry
Peptides - metabolism
Polyamines - chemistry
Polyamines - metabolism
Polyethylene Glycols
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Summary:PEGylated polyamidoamine (PAMAM) dendrimers as drug carriers have been a topic of interest because of their biomedically favorable features, including minimal toxicity, reduced immunogenicity, and excellent solubility in aqueous and most organic solutions. A PEG shell on dendrimer surface may provide steric hindrance, known as stealth properties of PEG, to stabilize drug molecules to be delivered. In this article, the effects of PEG and coupling sequence of drug, PEG, and dendrimer in modulating the stability of delivered drug molecules were evaluated. N‐succinyl‐Ala‐Ala‐Pro‐Phe‐p‐nitroanilide was chosen as a model peptide. Dendritic peptides, that is, peptide‐dendrimer, peptide‐PAMAM‐PEG, and peptide‐PEG‐dendrimer, were constructed based on Starburst™ G3.0 PAMAM dendrimer and characterized by 1H‐NMR spectroscopy. Hydrolysis of dendritic peptides was catalyzed by α‐chymotrypsin in pH 7.4 PBS buffer containing 5% DMF (v/v) at room temperature. The enzymatic stability of dendritic peptides was peptide‐PAMAM‐PEG > peptide‐PAMAM > free peptide > peptide‐PEG‐PAMAM. The ratio of PEG/peptide could be reduced for increasing peptide loading while maintaining the delivered peptides' relatively high enzymatic stability. The quantitative analysis of dendritic peptide/enzyme interactions provided the understandings of the molecular structure/stability relationships of dendrimer/drug for the design of an optimal PEGylated dendrimer‐based drug‐delivery system. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
ISSN:1549-3296
1552-4965
DOI:10.1002/jbm.a.30529