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Engineered peptides with enzymatically cleavable domains for controlling the release of model protein drug from “soft” nanoparticles

Paper ID Volume ID Publish Year Pages File Format Full-Text
1464 84 2012 10 PDF Available
Title
Engineered peptides with enzymatically cleavable domains for controlling the release of model protein drug from “soft” nanoparticles
Abstract

Matrix metalloproteinase-2 (MMP-2) is an endopeptidase that has been shown to be present in high concentrations during most tissue remodeling events, including disease states like active tumor sites, thus making it an attractive molecule for use in effecting local delivery of therapeutic molecules. Moreover, the use of non-toxic and biodegradable nanoparticles for controlled drug delivery is highly sought after. To this end, bovine serum albumin (BSA) nanoparticles (NPs) were stabilized with coatings formed using domains of varying sensitivity to MMP-2, viz. K6GPQG/IASQK6 and K6HPVG/LLARK6, lysine residues being used to facilitate peptide immobilization to the BSA NPs via electrostatic interactions, and peptide domains that have a high (HPVG/LLAR) and low (GPQG/IASQ) MMP-2 cleavage rate. The MMP-2-induced cleavage rates of these two domains (the position of action being noted with a “/”) have differing kinetics that can be used to provide a novel mechanism for facilitating the controlled release of molecules where local concentrations of MMP-2 are high. It was found that both surface concentration and cleavage domain type influenced the release of the model drug (BSA) from these NPs. This stratagem may provide a novel pathway for developing multi-functional coatings for controlling the local delivery of therapeutics at sites where the presence of various enzymes exist as a function of tissue state.

Keywords
BSA; Coacervation; Engineered peptide; MMP-2; Controlled release strategy
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Engineered peptides with enzymatically cleavable domains for controlling the release of model protein drug from “soft” nanoparticles
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Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 8, Issue 2, February 2012, Pages 636–645
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us