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Hydrolysable core-crosslinked thermosensitive polymeric micelles: Synthesis, characterisation and in vivo studies

Paper ID Volume ID Publish Year Pages File Format Full-Text
10364 681 2007 13 PDF Available
Title
Hydrolysable core-crosslinked thermosensitive polymeric micelles: Synthesis, characterisation and in vivo studies
Abstract

In this study, core-crosslinked (CCL) biodegradable thermosensitive micelles based on mPEG5000 and N-(2-hydroxyethyl)methacrylamide)-oligolactates (mPEG-b-p(HEMAm-Lacn)) were synthesised and their properties investigated. Rapidly heating aqueous solutions of partially methacrylated block copolymers to above their critical micelle temperature (CMT), followed by illumination in presence of a photoinitiator yielded almost monodisperse CCL micelles with a size of 68±7 nm. Either below the CMT or after addition of sodium dodecyl sulphate, the non-crosslinked (NCL) micelles rapidly disintegrated whereas the CCL micelles kept their integrity. NCL micelles fell apart after 5 h in pH 7.4 at 37 °C as a result of the hydrolysis of lactate side chains, whereas the CCL micelles had a much higher stability and only degraded after cleavage of the ester bonds in the crosslinks. The circulation kinetics and biodistribution of CCL micelles were considerably better than those of NCL micelles, i.e., 58% of the injected dose (ID) of CCL versus 6% of NCL micelles was recovered in the circulation 4 h post-injection. Furthermore, the liver uptake of the CCL micelles (10% ID) was much lower than that of the NCL micelles (24% ID) 4 h after administration, while tumour accumulation was almost 6 times higher for the CCL micelles. Likely, NCL micelles dissociated after i.v. administration and/or were opsonised and captured by macrophages while the dense PEG shell of CCL micelles made them less prone towards opsonisation. The excellent physical stability of these degradable CCL micelles and very favourable biodistribution profile renders them very suitable for drug targeting purposes.

Keywords
Self-assembly; Micelle; Photopolymerisation; Crosslinking; Biodegradation; Poly(ethylene glycol)
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Hydrolysable core-crosslinked thermosensitive polymeric micelles: Synthesis, characterisation and in vivo studies
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 28, Issue 36, December 2007, Pages 5581–5593
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