Organogels from trehalose difatty ester amphiphiles.

Saccharide diesters have been recently shown to be excellent gelators of vegetable oils. In this paper, different fatty acid trehalose diesters were synthesized by a selective enzymatic transesterification performed only on the primary hydroxyl group of the trehalose. The resulting trehalose diesters demonstrated their ability to self-assemble in a large variety of edible vegetable oils with a minimum gelation concentration of 0.25 wt%/v. Microscopic analysis and X-ray scattering studies indicate that the gels are obtained by the self-assembly of trehalose diesters in crystalline fibers constituting the tridimensional network. The rheological study revealed that the properties of the gels depend on the kind of fatty acid grafted on the trehalose but are also influenced by the vegetable oil composition.

The combination of block copolymers and phospholipids to form giant hybrid unilamellar vesicles (GHUVs) does not systematically lead to "intermediate" membrane properties.

In this work, the elasticity under stretching as well as the fluidity of Giant Hybrid Unilamellar Vesicles (GHUV) has been studied. The membrane structuration of these GHUVs has already been studied at the micro and nanoscale in a previous study of the team. These GHUVs were obtained by the association of a fluid phospholipid (POPC) and a triblock copolymer, poly(ethyleneoxide)-b-poly(dimethylsiloxane)-b-poly(ethyleneoxide). Although the architecture of triblock copolymers can facilitate vesicle formation, they have been scarcely used to generate GHUVs. We show, through micropipette aspiration and FRAP experiments, that the incorporation of a low amount of lipids in the polymer membrane leads to a significant loss of the toughness of the vesicle and subtle modification of the lateral diffusion of polymer chains. We discuss the results within the framework of the conformation of the triblock copolymer chain in the membrane and in the presence of lipid nanodomains.

Mixing Block Copolymers with Phospholipids at the Nanoscale: From Hybrid Polymer/Lipid Wormlike Micelles to Vesicles Presenting Lipid Nanodomains.

Hybrids, i.e., intimately mixed polymer/phospholipid vesicles, can potentially marry in a single membrane the best characteristics of the two separate components. The ability of amphiphilic copolymers and phospholipids to self-assemble into hybrid membranes has been studied until now on the submicrometer scale using optical microscopy on giant hybrid unilamellar vesicles (GHUVs), but limited information is available on large hybrid unilamellar vesicles (LHUVs). In this work, copolymers based on poly(dimethylsiloxane) and poly(ethylene oxide) with different molar masses and architectures (graft, triblock) were associated with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Classical protocols of LUV formation were used to obtain nanosized self-assembled structures. Using small-angle neutron scattering (SANS), time-resolved Förster resonance energy transfer (TR-FRET), and cryo-transmission electron microscopy (cryo-TEM), we show that copolymer architecture and molar mass have direct influences on the formation of hybrid nanostructures that can range from wormlike hybrid micelles to hybrid vesicles presenting small lipid nanodomains.

Phase Separation and Nanodomain Formation in Hybrid Polymer/Lipid Vesicles.

Hybrid polymer/lipid large unilamellar vesicles (LUVs) were studied by small angle neutron scattering (SANS), time-resolved Förster resonance energy transfer (TR-FRET), and cryo-transmission electron microscopy (cryo-TEM). For the first time in hybrid vesicles, evidence for phase separation at the nanoscale was obtained, leading to the formation of stable nanodomains enriched either in lipid or polymer. This stability was allowed by using vesicle-forming copolymer with a membrane thickness close to the lipid bilayer thickness, thereby minimizing the hydrophobic mismatch at the domain periphery. Hybrid giant unilamellar vesicles (GUVs) with the same composition have been previously shown to be unstable and susceptible to fission, suggesting a role of curvature in the stabilization of nanodomains in these structures.

Recent trends in the tuning of polymersomes' membrane properties.

"Polymersomes" are vesicular structures made from the self-assembly of block copolymers. Such structures present outstanding interest for different applications such as micro- or nano-reactor, drug release or can simply be used as tool for understanding basic biological mechanisms. The use of polymersomes in such applications is strongly related to the way their membrane properties are controlled and tuned either by a precise molecular design of the constituting block or by addition of specific components inside the membrane (formulation approaches). Typical membrane properties of polymersomes obtained from the self-assembly of "coil coil" block copolymer since the end of the nineties will be first briefly reviewed and compared to those of their lipidic analogues, named liposomes. Therefore the different approaches able to modulate their permeability, mechanical properties or ability to release loaded drugs, using macromolecular engineering or formulations, are detailed. To conclude, the most recent advances to modulate the polymersomes' properties and systems that appear very promising especially for biomedical application or for the development of complex and bio-mimetic structures are presented.

Biomimetic doxorubicin loaded polymersomes from hyaluronan-block-poly(gamma-benzyl glutamate) copolymers.

Using "click chemistry" as an easy and versatile synthetic strategy to combine hyaluronan and polyglutamate blocks, we have prepared nanovesicles (polymersomes) that present a controlled size, excellent colloidal stability, and a high loading capacity for hydrophilic and hydrophobic drugs. The unique feature of our concept is the use of hyaluronan, a polysaccharide with known capacity for targeting cancer-related protein receptors, as the hydrophilic portion of a block copolymer system. The cytotoxicity and internalization mechanism of doxorubicin-loaded polymersomes have been evaluated in C6 glioma tumor cell lines. The dual purpose served by hyaluronan, as both a hydrophilic block critical to vesicle formation and a binding agent for biological targets, breaks new ground in terms of multifunctional nanomaterial design for drug delivery.

Role of block copolymer nanoconstructs in cancer therapy.

Drug, gene, and protein delivery is a very challenging and exciting area in nanobiotechnology where block copolymers are increasingly considered especially as carriers for pharmacotherapy of various cancers. Cancer chemotherapy is particularly challenging because of nonselective distribution of drugs, associated severe toxicity, multidrug resistance, and chronic treatments influencing the quality-adjusted life of patients. These limitations lead to incomplete cure and render many drugs ineffective in treating cancers. Liposomes are currently more advanced in clinical trials and industrial developments but they lack stability and pose difficulties in functionalizing liposomes. More recently, various types of polymer-based nanoconstructs have been designed and synthesized, and are being investigated for the cancer chemotherapy applications. This review discusses the most significant and recent developments on specific self-assembled block copolymers as a carrier system such as micelles and vesicles, which can be successfully used to enhance the solubility of hydrophobic drugs, helpful in targeting selective sites in the body, delivering active molecules in a control manner, and reducing the side effects in the treatment of cancer.