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Polymer vesicles in vivo: correlations with PEG molecular weight
Peter J Photos1, Lucie Bacakova, Bohdana Discher
1Department of Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104-6393, USA.
Summary
Synthetic polymersomes offer superior circulation times compared to traditional PEGylated liposomes in vivo. These advanced vesicles demonstrate enhanced stealth properties, extending their presence in circulation by up to twofold.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Pharmacology
Background:
- Polyethylene glycol (PEG)-modified lipid vesicles (liposomes) are utilized to prolong circulation time.
- High PEGylation ratios are limited by vesicle curvature and PEG chain properties.
- Polymersomes, constructed from PEG-based block copolymers, offer greater design flexibility and stability.
Purpose of the Study:
- To evaluate the in vivo circulation characteristics of polymersomes with varying copolymer chain lengths.
- To compare the circulation times of polymersomes against traditional PEGylated liposomes (Stealth liposomes).
- To investigate the opsonization and phagocytic uptake mechanisms of polymersomes in plasma.
Main Methods:
- In vivo pharmacokinetic studies of polymersomes in rats.
- In vitro plasma incubation assays to assess opsonization.
- Optical trapping assays to evaluate phagocytic engulfment of opsonized polymersomes.
Main Results:
- Polymersomes exhibited in vivo circulation half-lives (tau(1/2)) up to twofold longer than Stealth liposomes.
- Circulation time dependence on PEG molecular weight was observed, with liver and spleen uptake remaining a limiting factor.
- Gradual opsonization via plasma protein adsorption was noted, delaying rapid phagocytic uptake.
Conclusions:
- Completely synthetic polymersomes extend the stealth effect observed with PEGylated liposomes.
- Polymersomes represent a promising platform for enhanced drug delivery and reduced vesicle clearance.
- Further research into optimizing polymersome design can overcome limitations related to RES uptake.