α-Acetal, ω-Alkyne Poly(ethylene oxide) as a Versatile Building Block for the Synthesis of Glycoconjugated Graft-Copolymers Suited for Targeted Drug Delivery

Abstract

α-Acetal, ω-alkyne poly(ethylene oxide) was synthesized as building block of glycoconjugated poly(ε-caprolactone)-graft-poly(ethylene oxide) (PCL-g-PEO) copolymers. The alkyne group is indeed instrumental for the PEGylation of a poly(α-azido-ε-caprolactone-co-ε-caprolactone) copolymer by the Huisgen's 1,3 dipolar cycloaddition, i.e., a click reaction. Moreover, deprotection of the acetal end-group of the hydrophilic PEO grafts followed by reductive amination of the accordingly formed aldehyde with an aminated sugar is a valuable strategy of glycoconjugation of the graft copolymer, whose micelles are then potential. A model molecule (fluoresceinamine) was first considered in order to optimize the experimental conditions for the reductive amination. These conditions were then extended to the decoration of the graft copolymer micelles with mannose, which is a targeting agent of dendritic cells and macrophages. The bioavailability of the sugar units at the surface of micelles was investigated by surface plasmon resonance (SPR). The same question was addressed to nanoparticles stabilized by the graft copolymer. Enzyme linked lectin assay (ELLA) confirmed the availability of mannose at the nanoparticle surface.

Sulindac encapsulation and release from functional poly(HEMA) microparticles prepared in supercritical carbon dioxide

“…Grafting of the fluoresceinamine was performed according to previously published conditions (Freichels et al, 2012). The procedure is described as follows: the UV-cleaved particles (100 mg, 1 equivalent of aldehyde groups) were suspended in 50 ml of phosphate buffer solution (500mM, pH: 7.4) and fluoresceinamine isomer 1 (2 equivalents) was added.…”

“…the fluoresceinamine on the particle surface by using reductive amination. Reported conditions for reductive amination reaction by Freichels et al (Freichels et al, 2012) have been followed as described in details in the experimental part. Extensive washing (i.e 3 days) by dialysis had been carefully performed after grafting.…”

Multifunctional polymeric micelles for delivery of drugs and siRNA

“…In vivo , they exhibited better anti-tumor efficacy and reduced toxicity compared to free DOX (Qiu et al, 2013). Other small molecules like biotin (Lin et al, 2013), galactose (Zhong et al, 2013), and mannose (Freichels et al, 2012) have also been reported for surface modification of polymeric micelles.…”

Carbohydrate PEGylation, an approach to improve pharmacological potency

“…Mannose residues as their 2-aminoethyl glycosides were attached by reductive amination to the surface of copolymer micelles of PEG with poly-ε-caprolactone for targeting dendritic cells and macrophages ( Fig. 4 ) [ 45 ]…”