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International audience; Delicate control over architectures via crystallization-driven self-assembly (CDSA) in aqueous solution, particularly combined with external stimuli, is rare and challenging. Here, we report a stepwise CDSA process thermally initiated from amphiphilic poly(N-allylglycine)-b-poly(N-octylglycine) (PNAG-b-PNOG) conjugated with thiol-terminated triethylene glycol monomethyl ethers ((PNAG-g-EG3)-b-PNOG) in aqueous solution. The diblock copolymers show a reversible thermoresponsive behavior with nearly identical cloud points in both heating and cooling runs. In contrast, the morphology transition of the assemblies is irreversible upon a heating–cooling cycle because of the presence of a confined domain arising from crystalline PNOG, which allows for the achievement of different nanostructured assemblies by the same polymer. We demonstrated that the thermoresponsive property of PNAG-g-EG3 initiates assembly kinetically that is subsequently promoted by crystallization of PNOG thermodynamically. The irreversible morphology transition behavior provides a convenient platform for comparing the cellular uptake efficiency of nanostructured assemblies with various morphologies that are otherwise similar.

International audience; In this work, a series of poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) diblock copolymers with relatively short PLGA blocks were synthesized by ring-opening polymerization of D,L-lactide and glycolide in the presence of monomethoxy PEG with Mn of 2000. Spherical micelles were obtained by self-assembly of copolymers using direct dissolution method. The degradation of the micelles was investigated under in vitro conditions at 37 degrees C. The effects of chemical composition on micelle degradation were evaluated from NMR, GPC, DLS and TEM measurements. The molar mass of copolymers constantly decreases during degradation in all cases. The copolymers with longer hydrophobic PLGA blocks exhibit larger molar mass decrease rate since only the PLGA block is degradable. Meanwhile, the molar mass distribution remains almost unchanged, in agreement with random chain cleavage. NMR spectra show that the final degradation products are lactic acid and glycolic acid. A pH decrease is also detected during degradation. The size of the micelle depends on the chemical composition of copolymers. Micelle size is smaller for copolymers with longer hydrophobic PLGA blocks because of more compact core structure. With the hydrolysis of the PLGA blocks, the structure of micelles becomes looser, and the micelle size exhibits a sharp increase after a lag time. At the later stage of degradation, the size of micelles decreases as they become unstable and could collapse. The micelle structure could be clearly distinguished after 45 days degradation for copolymers with longer PLGA blocks, whereas those with shorter PLGA blocks lost the structural integrity. It is also noteworthy that the LA/GA ratio has little effect on the degradation of PLGA-PEG copolymer micelles, which may be related to the amorphous structure of PLGA block and the relatively short block length. These findings should be helpful for the conception of drug delivery systems based on PLGA-PEG micelles.

International audience; A series of poly(e-caprolactone/glycolide)-poly(ethylene glycol) (P(CL/GA)-PEG) diblock copolymers were prepared by ring opening polymerization of a mixture of e-caprolactone and glycolide using mPEG as macro-initiator and stannous octoate as catalyst. Self-assembled micelles were prepared from the copolymers using nanoprecipitation method. The micelles were spherical in shape. The micelle size was larger for copolymers with longer PEG blocks. In contrast, the critical micelle concentration of copolymers increased with decreasing the overall hydrophobic block length. Drug loading and drug release studies were performed under in vitro conditions, using paclitaxel as a hydrophobic model drug. Higher drug loading was obtained for micelles with longer poly(epsilon-caprolactone) blocks. Faster drug release was obtained for micelles of mPEG2000 initiated copolymers than those of mPEG5000 initiated ones. Higher GA content in the copolymers led to faster drug release. Moreover, drug release rate was enhanced in the presence of lipase from Pseudomonas sp., indicating that drug release is facilitated by copolymer degradation. The biocompatibility of copolymers was evaluated from hemolysis, dynamic clotting time, and plasma recalcification time tests, as well as MTT assay and agar diffusion test. Data showed that copolymer micelles present outstanding hemocompatibility and cytocompatibility, thus suggesting that P(CL/GA)-PEG micelles are promising for prolonged release of hydrophobic drugs.

International audience; A series of poly(2-ethyl-2-oxazoline)-poly(L-lactide) (PEOz-PLA) diblock copolymers were synthesized by ring-opening polymerization of L-lactide using a monohydroxy terminated PEOz-OH macro-initiator in the presence of stannous octoate as catalyst. The resulting diblock copolymers were characterized by H-1 nuclear magnetic resonance and gel permeation chromatography. Self-assembled micelles were prepared using the co-solvent evaporation method in water and in phosphate buffered saline (PBS) at pH 7.4, 6.5 and 5.0. The resulting micelles exhibit different morphologies, such as spherical micelles and worm-like micelles depending on the hydrophilic/hydrophobic balance. Spherical micelles were exclusively observed for PEOz-PLA copolymers with short PLA blocks, whereas co-existence of worm-like and spherical micelles was observed for copolymers with long PLA blocks. The micelle size increases with decreasing pH due to the electrostatic repulsion between PEOz chains resulting from ionization of the tertiary amide groups along PEOz chains. A hydrophobic anti-tumor drug, paclitaxel, was entrapped in PEOz-PLA micelles. High loading efficiency up to 86.7% was obtained for copolymers with long PLA blocks. Drug release was performed in PBS at different pH values. During the 30-day release period, faster release was obtained for copolymers with shorter PLA blocks than for copolymers with longer PLA blocks, at acidic pH than at pH 7.4. It is thus concluded that pH-responsive PEOz-PLA copolymer micellss could be promising as carrier of anti-tumor drugs.

A series of poly(ethylene glycol)-polylactide (PEG-PLA) diblock copolymers were synthesized by ring-opening polymerization of l-lactide using monomethoxy PEG as macroinitiator and zinc lactate as catalyst. Filomicelles were prepared from the resulting copolymers by co-solvent evaporation method. The biocompatibility of the various filomicelles was evaluated with the aim of assessing their potential as drug carriers. Various aspects of biocompatibility were considered, including agar diffusion test, MTT assay, release of cytokines, hemolytic test, dynamic clotting time, protein adsorption in vitro, and zebrafish embryonic compatibility in vivo. The results revealed that the filomicelles present good cytocompatibility and hemocompatibility in vitro. Moreover, the cumulative effects of filomicelles throughout embryos deveploping stages have no toxicity in vivo. It is thus concluded that filomicelles prepared from PEG-PLA copolymers with outstanding biocompatibility are promising as potential drug car...