Synthesis of Poly(lactide-co-glycolide-co-ε-caprolactone)-graft-mannosylated Poly(ethylene oxide) Copolymers by Combination of “Clip” and “Click” Chemistries
(2012) Biomacromolecules — Vol. 13, n° 3, p. 760-768 (2012)
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Synthesis-of-polylactide-co-glycolide-co--caprolactone-graft--mannosylated-polyethylene-oxide-copolymers-by-combination-of-clip-and-clic.pdf
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- Poly(lactide-co-glycolide) (PLGA) is extensively used in pharmaceutical applications, for example, in targeted drug delivery, because of biocompatibility and degradation rate, which is easily tuned by the copolymer composition. Nevertheless, synthesis of sugar-labeled amphiphilic copolymers with a PLGA backbone is quite a challenge because of high sensitivity to hydrolytic degradation. This Article reports on the synthesis of a new amphiphilic copolymer of PLGA grafted by mannosylated poly(ethylene oxide) (PEO). A novel building block, that is, α-methoxy-ω-alkyne PEO-clip-N-hydroxysuccinimide (NHS) ester, was prepared on purpose by photoreaction of a diazirine containing molecular clip. This PEO block was mannosylated by reaction of the NHS ester groups with an aminated sugar, that is, 2-aminoethyl-α-D-mannopyroside. Then, the alkyne ω-endgroup of PEO was involved in a copper alkyne- azide coupling (CuAAC) with the pendent azides of the aliphatic copolyester. The targeted mannose-labeled poly(lactide-co-glycolide-co-ε-caprolactone)-graf t-poly(ethylene oxide) copolymer was accordingly formed. Copolymerization of D,L-lactide and glycolide with α-chloro-ε-caprolactone, followed by substitution of chlorides by azides provided the azido-functional PLGA backbone. Finally, micelles of the amphiphilic mannosylated graft copolymer were prepared in water, and their interaction with Concanavalin A (ConA), a glyco-receptor protein, was studied by quartz crystal microbalance. This study concluded to the prospect of using this novel bioconjugate in targeted drug delivery.
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Freichels, H., Pourcelle, V., Auzély-Velty, R., Marchand-Brynaert, J., & Jérôme, C. (2012). Synthesis of Poly(lactide-co-glycolide-co-ε-caprolactone)-graft-mannosylated Poly(ethylene oxide) Copolymers by Combination of “Clip” and “Click” Chemistries. Biomacromolecules, 13(3), 760-768. https://doi.org/10.1021/bm201690w (Original work published 2012)