Journal
JOURNAL OF CONTROLLED RELEASE
Volume 151, Issue 2, Pages 104-109Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2011.02.011
Keywords
Intravital confocal microscopy; Polyplex; Polyethylene glycol; Block copolymer; Polymer micelle
Funding
- Japan Science and Technology Corporation (JST)
- Japan Society for the Promotion of Science (JSPS)
- Grants-in-Aid for Scientific Research [21659299, 23350049, 11J08266, 23390009] Funding Source: KAKEN
Ask authors/readers for more resources
Surface modification using poly(ethylene glycol) (PEG) is a widely used strategy to improve the biocompatibility of cationic polymer-based nonviral gene vectors (polyplexes). A novel method based on intravital real-time confocal laser scanning microscopy (IVRTCLSM) was applied to quantify the dynamic states of polyplexes in the bloodstream, thereby demonstrating the efficacy of PEGylation to prevent their agglomeration. Blood flow in the earlobe blood vessels of experimental animals was monitored in a noninvasive manner to directly observe polyplexes in the circulation. Polyplexes formed distinct aggregates immediately after intravenous injection, followed by interaction with platelets. To quantify aggregate formation and platelet interaction, the coefficient of variation and Pearson's correlation coefficient were adopted. In contrast, polyplex micelles prepared through self-assembly of plasmid DNA with PEG-based block catiomers had dense PEG palisades, revealing no formation of aggregates without visible interaction with platelets during circulation. This is the first report of in situ monitoring and quantification of the availability of PEGylation to prevent polyplexes from agglomeration over time in the blood circulation. This shows the high utility of IVRTCLSM in drug and gene delivery research. (C) 2011 Elsevier 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