References of "Cajot, Sébastien"
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See detailCore cross-linked micelles of polyphosphoester containing amphiphilic block copolymers as drug nanocarriers
Ergül, Zeynep ULg; Vanslambrouck, Stéphanie; Cajot, Sébastien et al

in RSC Advances (2016), 6(48), 42081-42088

Poly(ethylene oxide)-b-polyphosphoester amphiphilic block copolymers are known to self-assemble into polymer micelles when dissolved into water. This work aims at reporting on the improvement of the ... [more ▼]

Poly(ethylene oxide)-b-polyphosphoester amphiphilic block copolymers are known to self-assemble into polymer micelles when dissolved into water. This work aims at reporting on the improvement of the stability of the micelles at high dilution by crosslinking the hydrophobic polyphosphoester micellar core. Typically, an unsaturated alkene side-chain was introduced on the cyclic phosphate monomer according to a one-step reaction followed by its organocatalyzed polymerization initiated by a poly(ethylene oxide) macroinitiator. This strategy avoids the use of any organometallic compounds in order to facilitate the purification and meet the stringent requirements of biomedical applications. After self-assembly into water, the micelles were cross-linked by simple UV irradiation. These cross-linked micelles have then been loaded by doxorubicin to evaluate their potential as drug nanocarriers and monitor the impact of crosslinking on the release profile. [less ▲]

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See detailSmart cross-linked polymer micelles for drug delivery
Riva, Raphaël ULg; Vanslambrouck, Stéphanie ULg; Ergül, Zeynep ULg et al

Conference (2014, November 11)

Nowadays, polymer crosslinking is widely used in industry to improve or to impart new properties to existing polymer material. In the pharmaceutical field, polymer crosslinking is of great interest for ... [more ▼]

Nowadays, polymer crosslinking is widely used in industry to improve or to impart new properties to existing polymer material. In the pharmaceutical field, polymer crosslinking is of great interest for the elaboration of drug delivery devices, mostly hydrogels. Nevertheless, crosslinking is also very useful in nanovectorization of active principle. Indeed, each day, new drugs are synthesized and available on the market but in too many cases, the high hydrophobicity of some drugs makes them useless because of the absence of an appropriated administration method. The encapsulation of the drug into a nanocarrier, typically in the hydrophobic core of a polymer micelle, allows a significant increase of the drugs concentration in water in addition to the protection of the active principle against degradation. However, polymer micelles suffer of the main drawback to not be stable, leading to a premature release of the drug, when the concentration falls down the critical micellar concentration (CMC), which it is rapidly observed after intravenous injection. In order to get rid of the CMC, crosslinking of the micelle core is the most proposed strategy. Nevertheless, the crosslinking of the micelle core may have a non-negligible effect on the drug loading but mainly on the drug release due to the sequestration of the drug in the network. Over the last years, our lab investigated several strategies for the crosslinking of the micelle core made of amphiphilic and biocompatible block copolymers generally by UV radiation in order to fulfill the increasingly stringent requirements of biomedical applications. These strategies are very helpful to prepare injectable nanosized cross-linked particles loaded with an active particle. For some systems, the effect of the crosslinking rate on the drug loading and the drug release was evaluated using a model drug. As the crosslinking may interfere with the drug release after internalization of the carrier into the cell, a reversible crosslinking of the micelle core was proposed. Typically, the introduction of disulfide bond as inter-chain links allowed to delay the drug release by diffusion whereas into the cell, the reduction of the disulfide bridges into corresponding thiol led to the fast disassemble of the micelle and the specific release of the drug into cytoplasm. [less ▲]

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See detailReversibly cross-linked polymer micelle as smart drug dellivery device
Lecomte, Philippe ULg; Riva, Raphaël ULg; Cajot, Sébastien et al

Conference (2013, November 20)

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See detailTailor made amphiphilic copolymers for the design of smart drug delivery systems
Riva, Raphaël ULg; Cajot, Sébastien; Jérôme, Christine ULg

Conference (2013, August 21)

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See detailIn vitro investigations of smart drug delivery systems based on redox-sensitive cross-linked micelles
Cajot, Sébastien; Schol, D.; Dahnier, F. et al

in Macromolecular Symposia (2013), 13(12), 1661-1670

Redox-sensitive micelles are designed by using block copolymers of different architectures composed of a hydrophilic block of poly(ethylene oxide), and hydrophobic blocks of poly(ϵ-caprolactone) and poly ... [more ▼]

Redox-sensitive micelles are designed by using block copolymers of different architectures composed of a hydrophilic block of poly(ethylene oxide), and hydrophobic blocks of poly(ϵ-caprolactone) and poly(α-azide-ϵ-caprolactone). Stability of these micelles is insured in diluted media by cross-linking their core via the addition of a bifunctional cross-linker, while redox sensitivity is provided to these micelles by inserting a disulfide bridge in the cross-linker. The potential of these responsive micelles to be used as nanocarriers is studied in terms of cytotoxicity and cellular internalization. The release profiles are also investigated by varying the environment reductive strength. [less ▲]

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See detailNovel functional degradable block copolymers for the building of reactive micelles
Cajot, Sébastien; Lecomte, Philippe ULg; Jérôme, Christine ULg et al

in Polymer Chemistry (2013), 4(4), 1025-1037

Amphiphilic biocompatible copolymers are promising materials for the elaboration of nanosystems for drug delivery applications. This paper aims at reporting on the synthesis of new functional amphiphilic ... [more ▼]

Amphiphilic biocompatible copolymers are promising materials for the elaboration of nanosystems for drug delivery applications. This paper aims at reporting on the synthesis of new functional amphiphilic copolymers based on biocompatible and bioeliminable blocks. Poly(ethylene oxide) was selected as the hydrophilic block, whereas an aliphatic polyester, i.e. poly(epsilon-caprolactone), or a polycarbonate, i.e. poly(trimethylene carbonate), were chosen as the degradable hydrophobic block. In order to allow a post-functionalization of the micelles core, azide groups were introduced on the hydrophobic segment to provide reactivity towards functional alkyne derivatives by the copper azide-alkyne cycloaddition (CuAAC). For this purpose, a functional lactone, i.e. alpha-chloro-epsilon-caprolactone was introduced during the polymerization of the hydrophobic block before being converted into azide on the preformed copolymer. Such reactivity of the block copolymers and their self-assemblies is of prime interest for drugs or fluorescent dyes grafting, so as for micelles cross-linking. The influence of the azides distribution along the degradable block on the micelles post-functionalization ability has been studied by using alkyne bearing fluorescent dyes as model for drugs. The hydrophilicity of the dye on the micelles post-functionalization efficiency has also been investigated. [less ▲]

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See detailSmart nanocarriers for pH-triggered targeting and release of hydrophobic drugs
Cajot, Sébastien; Van Butsele, Kathy; Paillard, A. et al

in Acta Biomaterialia (2012), 8(12), 4215-4223

The use of hybrid pH-sensitive micelles mainly based on the PEO129-P2VP43-PCL17 ABC miktoarm star copolymer as potential triggered drug delivery systems has been investigated. Co-micellization of this ... [more ▼]

The use of hybrid pH-sensitive micelles mainly based on the PEO129-P2VP43-PCL17 ABC miktoarm star copolymer as potential triggered drug delivery systems has been investigated. Co-micellization of this star copolymer with a second copolymer labeled by a targeting ligand, i.e. biotin, on the pH sensitive block (poly-2-vinylpyridine, P2VP) has been considered here in order to impart possible active targeting of the tumor cells. Two architectures have been studied for these labeled copolymers, i.e. a miktoarm star or a linear ABC terpolymer and the respective hybrid micelles have been compared in terms of cytotoxicity (cells viability) and cellular uptake (by using fluorescent dye loaded micelles). Finally, the triggered drug release in the cytosol of tumor cells was investigated by studying on one hand the lysosomal integrity after internalization and on the other hand the release profile in function of the pH. [less ▲]

Detailed reference viewed: 90 (17 ULg)
See detailFunctional degradable polymers for advanced drug delivery systems
Cajot, Sébastien; Riva, Raphaël ULg; Jérôme, Christine ULg

Conference (2012, September)

Nowadays, polymer micelles have attracted an increasing interest in pharmaceutical research because they could be used as efficient drug delivery systems. Micelles of amphiphilic block copolymers are ... [more ▼]

Nowadays, polymer micelles have attracted an increasing interest in pharmaceutical research because they could be used as efficient drug delivery systems. Micelles of amphiphilic block copolymers are supramolecular core-shell type assemblies of several tens of nanometers in diameter. In principle, the micelle core is usually constructed with biodegradable hydrophobic polymers such as aliphatic polyesters, e.g. poly(ε-caprolactone) (PCL), which serves as a reservoir for the incorporation of various lipophilic drugs. Water soluble poly(ethylene oxide) (PEO) is most frequently used to build the micelle corona because it is very efficient in preventing protein adsorption at surfaces and in stabilizing micelles in the blood compartment, making particles invisible to the body defense system. Even if micelles get a high stability in aqueous media thanks to their low critical micellar concentration, micelle dissociation is not always preserved when they are injected in the blood compartment. A way to provide the micelle stability during their administration is to cross-link them. Different kinds of cross-linked micelles can be investigated depending on the localization of the cross-linking. Shell cross-linked micelles or nanocage structures with a degradable core have the great advantage to reach drug encapsulation with a high loading rate. However, cross-linking the hydrophilic shell may affect the stealthiness of the carrier. Thus, we have designed reversibly cross-linked micelles by introducing the cross-linking bridges in the hydrophobic segment of the block copolymer, rather than in the hydrophilic one, leading so to more internal cross-linking and thus preserving the mobility of the hydrophilic segment. Three different localizations of the cross-linking has been targeted; (i) loose core cross-linking of a core-corona system, (ii) tight core cross-linking of a core-shell-corona system (the shell and the core being both hydrophobic and the corona hydrophilic) and (iii) tight shell cross-linking of a similar core-shell-corona system. To reach this goal, three types of amphiphilic copolymers have been used bearing pendent azide groups in the hydrophobic segment. These copolymers have been obtained by starting the ring-opening polymerization of ε-CL and a functional CL, either as a mixture or sequentially from a poly(ethylene oxide) macroinitiator leading to the three targeted architectures. The azide groups located along the PCL backbone have then been used to cross-link the micelles by the Huisgens cycloaddition with a bis-alkyne cross-linker. The choice of this cross-linker has also taken into account the requirement to make the cross-linking reversible. For that purpose, disulfide bridges have been selected in order to impart reversibility to the cross-linking by intracellular reduction. Indeed, the marked concentration difference of glutathione between extra- and intra-cellular environments has already been used to trigger drug release by intracellular disulfide bond cleavage. Accordingly, a bis-alkyne disulfide molecule has been chosen as cross-linker. The micellization and cross-linking of these amphiphilic azido macromolecules have been studied. The reversibility of the cross-linking in reductive environment and the cross-linked micelles stealthiness have been tested. [less ▲]

Detailed reference viewed: 31 (1 ULg)