Polyester nanoparticles presenting mannose residues : toward the development of new vaccine delivery systems combining biodegradability and targeting properties

in Biomacromolecules (2009), 10(3), 651-657

We report the synthesis of fully biodegradable polymeric nanoparticles presenting mannose residues at their surface and their interaction with lectins. A simple and versatile method was used to reach the ... [more ▼]

We report the synthesis of fully biodegradable polymeric nanoparticles presenting mannose residues at their surface and their interaction with lectins. A simple and versatile method was used to reach the surface functionalization of poly(d,l-lactic acid) (PLA) nanoparticles by mannose moieties: It consists in using an amphiphilic mannosylated poly(ethylene oxide)-b-poly(-caprolactone) (PEO-b-PCL) diblock copolymer as a bioresorbable surface modifier in a simple nanoprecipitation-evaporation procedure. The size and zeta potential of the nanoparticles were found to depend on the molar copolymer/PLA ratio, demonstrating the influence of the copolymer on the formation of the nanoparticles. The bioavailability of the mannose residues as specific recognition sites on the nanoparticle surface could be demonstrated by a modified enzyme-linked lectin assay (ELLA) using biotin-labeled lectins which interact specifically with α-d-mannopyrannoside derivatives. Besides specific interaction by lectin−mannose complex formation, nonspecific adsorption of the proteins on the nanoparticle surface was observed. These results were fully supported by isothermal titration calorimetry experiments which suggested that the balance between specific and nonspecific interactions can be controlled by the amount of glycosylated polymer used for the preparation of the nanoparticles. Such nanoparticles are expected to be specifically recognized by mannose receptors, which are highly expressed in cells of the immune system. The targeting properties of these carrier systems combined with their potential adjuvant effects due to their size in the range of 200−300 nm make them attractive candidates as vaccine delivery systems. [less ▲]

Surfactant-free synthesis of amphiphilic poly(ethylene oxide)-b-poly(n-butyl acrylate) copolymers by ab initio batch emulsion polymerization under RAFT control

Poster (2008, August 19)

Mannosylated poly(ethylene oxide)-b-Poly(epsilon-caprolactone) diblock copolymers: Synthesis, characterization, and interaction with a bacterial lectin

in Biomacromolecules (2007), 8(9), 2717-2725

A novel bioeliminable amphiphilic poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-b-PCL) diblock copolymer end-capped by a mannose residue was synthesized by sequential controlled polymerization of ... [more ▼]

A novel bioeliminable amphiphilic poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-b-PCL) diblock copolymer end-capped by a mannose residue was synthesized by sequential controlled polymerization of ethylene oxide and epsilon-caprolactone, followed by the coupling of a reactive mannose derivative to the PEO chain end. The anionic polymerization of ethylene oxide was first initiated by potassium 2-dimethylaminoethanolate. The ring-opening polymerization of epsilon-caprolactone was then initiated by the omega-hydroxy end-group of PEO previously converted into an Al alkoxide. Finally, the saccharidic end-group was attached by quaternization of the tertiary amine (alpha-end-group of the PEO-b-PCL with a brominated mannose derivative. The copolymer was fully characterized in terms of chemical composition and purity by high-resolution NMR spectroscopy and size exclusion chromatography. Furthermore, measurements with a pendant drop tensiometer showed that both the mannosylated copolymer and the non-mannosylated counterpart significantly decreased the dichloromethane/water interfacial tension. Moreover, these amphiphilic copolymers formed monodisperse spherical micelles in water with an average diameter of similar to 11 nin as measured by dynamic light scattering and cryo-transmission electron microscopy. The availability of mannose as a specific recognition site at the surface of the micelles was proved by isothermal titration microcalorimetry (ITC), using the BclA lectin (from Burkholderia cenocepacia), which interacts selectively with a-D-mannopyranoside derivatives. The thermodynamic parameters of the lectin/mannose interaction were extracted from the ITC data. These colloidal systems have great potential for drug targeting and vaccine delivery systems. [less ▲]

Heterograft copolymers of poly(epsilon-caprolactone) prepared by combination of ATRA "grafting onto" and ATRP "grafting from" processes

in Journal of Polymer Science Part A-Polymer Chemistry (2006), 44(20), 6015-6024

This paper aims at reporting on the synthesis of a heterograft copolymer by combining the "grafting onto" process based on atom transfer radical addition (ATRA) and the "grafting from" process by atom ... [more ▼]

This paper aims at reporting on the synthesis of a heterograft copolymer by combining the "grafting onto" process based on atom transfer radical addition (ATRA) and the "grafting from" process by atom transfer radical polymerization (ATRP). The statistical copolymerization of epsilon-caprolactone (epsilon-CL) and alpha-chloro-epsilon-caprolactone (alpha-Cl-epsilon-CL) was initiated by 2,2-dibutyl-2-stanna-1,3-dioxepane (DSDOP), followed by ATRA of parts of the chlorinated units of poly(alpha-Cl-epsilon-CL-co-epsilon CL) on the terminal double bond of alpha-MeO,omega-CH2=CH-CH2-CO2-poly(ethylene oxide) (PEO). The amphiphilic poly(epsilon CL-g-EO) graft copolymer collected at this stage forms micelles as supported by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The unreacted pendant chloro groups of poly(epsilon-CL-g-EO) were used to initiate the ATRP of styrene with formation of copolymer with two populations of randomly distributed grafts, that is PEO and polystyrene [less ▲]

Synthesis of amphiphilic copolymers of poly(ethylene oxide) and poly(epsilon-caprolactone) with different architectures, and their role in the preparation of stealthy nanoparticles

in Advanced Functional Materials (2006), 16(11), 1506-1514

Well-defined copolymers of biocompatible poly(epsilon-caprolactone) (PCL) and poly(ethylene oxide) (PEO) are synthesized by two methods. Graft copolymers with a gradient structure are prepared by ring ... [more ▼]

Well-defined copolymers of biocompatible poly(epsilon-caprolactone) (PCL) and poly(ethylene oxide) (PEO) are synthesized by two methods. Graft copolymers with a gradient structure are prepared by ring-opening copolymerization of epsilon-caprolactone (FCL) with a PEO macromonomer of the epsilon CL-type. The epsilon CL polymerization is initiated by a PEO macroinitiator to prepare diblock copolymers. These amphiphilic copolymers are used as stabilizers for biodegradable poly(DL-lactide) (PLA) nanoparticles prepared by a nanoprecipitation technique. The effect of the copolymer characteristic features (architecture, composition, and amount) on the nanoparticle formation and structure is investigated. The average size, size distribution, and stability of aqueous suspensions of the nanoparticles is measured by dynamic light scattering. For comparison, an amphiphilic random copolymer, poly(methyl methacrylate-co-methacrylic acid) (P(MMA-co-MA)), is synthesized. The stealthiness of the nanoparticles is analyzed in relation to the copolymer used as stabilizer. For this purpose, the activation of the complement system by nanoparticles is investigated in vitro using human serum. This activation is much less important whenever the nanoparticles are stabilized by a PEO-containing copolymer rather than by the P(MMA-co-MA) amphiphile. The graft copolymers with a gradient structure and the diblock copolymers with similar macromolecular characteristics (molecular weight and hydrophilicity) are compared on the basis of their capacity to coat PLA nanoparticles and to make them stealthy. [less ▲]

Design of stealth nanoparticles for drug delivery based on new amphiphilic copolymers

Conference (2006, May 18)

Novel architectures by ring-opening polymerization of lactones and lactides

Conference (2005, October 24)

Functionlization of biodegradable aliphatic polyesters by mannose-residue for the design of surface-modified polymeric nanoparticles

Conference (2005, June 01)

Versatile functionalization and grafting of poly(epsilon-caprolactone) by Michael-type addition

in Chemical Communications (2005), (2), 274-276

The Michael-type addition of aliphatic (co)polyesters onto gamma-acryloyloxy epsilon-caprolactone units is a very straightforward technique of functionalization and grafting, which is tolerant to a ... [more ▼]

The Michael-type addition of aliphatic (co)polyesters onto gamma-acryloyloxy epsilon-caprolactone units is a very straightforward technique of functionalization and grafting, which is tolerant to a variety of functional groups and does not require intermediate protection/deprotection steps. [less ▲]

PLA-coated gold nanoparticles for the labeling of PLA biocarriers

in Chemistry of Materials (2004), 16(5), 850-856

POly-DL-lactide end-capped by a protected thiol was synthesized by bulk ring-opening polymerization (ROP) of DL-lactide initiated by the reaction product of aluminum isopropoxide [Al (iOPr) (3)] with ... [more ▼]

POly-DL-lactide end-capped by a protected thiol was synthesized by bulk ring-opening polymerization (ROP) of DL-lactide initiated by the reaction product of aluminum isopropoxide [Al (iOPr) (3)] with alpha- (2,4-dinitrophenylsulfenyl) ethanol. After the thiol deprotection, PLA-SH was used to stabilize gold nanoparticles. Either these nanoparticles were prepared in the presence of PLA-SH, or PLA-SH was substituted for part of the undecanethiol (C11SH) that stabilized preformed gold nanoparticles. In contrast to C11SH-coated nanoparticles, those stabilized by PLA-SH were successfully entrapped into 100-nm PLA nanocarriers prepared by nanoprecipitation. This is an easy technique to label PLA biocarriers and therefore trace their fate in vivo. [less ▲]