Water-soluble, unimolecular containers based on amphiphilic multiarm star block copolymers

A new class of water-soluble, amphiphilic star block copolymers with a large number of arms was prepared by sequential atom transfer radical polymerization (ATRP) of n-butyl methacrylate (BMA) and poly-(ethylene glycol) methyl ether methacrylate (PEGMA). As the macroinitiator for the ATRP, a 2-bromoisobutyric acid functionalized fourth-generation hyperbranched polyester (Boltorn H40) was used, which allowed the preparation of star polymers that contained on average 20 diblock copolymer arms. The synthetic concept was validated by AFM experiments, which allowed direct visualization of single molecules of the multiarm star block copolymers. DSC and SAXS experiments on bulk samples suggested a microphase-separated structure, in agreement with the core-shell architecture of the polymers. SAXS experiments on aqueous solutions indicated that the star block copolymers can be regarded as unimolecular micelles composed of a PBMA core and a diffuse PPEGMA corona. The ability of the polymers to encapsulate and release hydrophobic guests was evaluated using 1H NMR spectroscopy. In dilute aqueous solution, these polymers act as unimolecular containers that can be loaded with up to 27 wt % hydrophobic guest molecules. © 2006 American Chemical Society.

Design of amphiphilic nanocapsules based on hyperbranched star-block copolymers for the encapsulation and the controlled release of olfactory compounds

Céline Ternat

Effective encapsulation of small, volatile, weakly water-soluble molecules such as flavors and fragrances is necessary to protect them from degradation, to increase their lifetime, and to improve their water dispersion and fixation depending on the substrate of interest. The aim of this project has been to improve encapsulation and release in order to optimize the performance of fragrance molecules in water-based household (detergents, softeners, etc.) and body care applications (shampoos, lotions, etc.), and fine perfumery applications. More specifically, the aim has been to investigate the effectiveness of "unimolecular micelles" based on amphiphilic multi-arm star-block copolymers with a hyperbranched core with more than 26 functional groups, a hydrophobic inner and a hydrophilic outer shell. These have been prepared from a commercial hyperbranched polyester macroinitiator (HBP) by ring-opening polymerization of ε-caprolactone, followed by the atom transfer radical polymerization (ATRP) of tert-butyl acrylate (tBuA). Hydrolysis of the tert-butyl groups has then been used to convert the poly(tBuA) blocks to poly(acrylic acid) (PAA), resulting in HBP-(PCL)p-(PAA)q pH-dependent amphiphilic star-block copolymers with good control of the molecular weight distribution. These were shown to form stable nanocapsules with a well defined core-shell architecture, as confirmed by thermal and microstructural characterization. The necessity of the core-shell architecture for the effective encapsulation of fragrance molecules in aqueous dispersion has been demonstrated by NMR (nuclear magnetic resonance). The extent of encapsulation reflects the dynamic equilibrium between the free molecules and the fragrance/polymer complex and is dependent on the octanol/water partition coefficient (logP) of the fragrance compounds, as demonstrated with a similar non ionic core-shell architecture HBP-(PBMA)37-(PPEGMA)39 composed of a hydrophobic poly(butyl methacrylate) (PBMA) core and a hydrophilic poly(polyethylene glycol) methyl ether methacrylate (PPEGMA) shell (provided by the Polymer Laboratory of the EPFL). The fragrance loadings in the polymer (HBP-(PCL)p-(PAA)q and HBP-(PBMA)37-(PPEGMA)39), which reached up to 30 wt% depending on the type of the fragrance molecule, were argued to be linked to their solubility in the hydrophobic core of the star-block copolymer. Moreover, under conditions representative of real applications (fine perfumery and softener applications) the star-block copolymers significantly extended the time over which the concentration of certain volatiles remained above the human olfactory threshold. Effective encapsulation and delayed release of small hydrophobic molecules was hence demonstrated to be possible with the present systems. The straightforward synthesis, tailorable chemistry and globular architecture of the star-block copolymers investigated here therefore offer promise for the development of relatively cheap encapsulants with affinities for specific components in fragrance packages, and release triggered by selected substrates according to their surface chemistry.

EPFL2007

Solution self-assembly of hybrid block copolymers containing poly(ethylene glycol) and amphiphilic peptide sequences

Harm-Anton Klok, Harald Nuhn

The self-assembly in aqueous solution of hybrid block copolymers consisting of amphiphilic ?-strand peptide sequences flanked by one or two PEG chains was investigated by means of circular dichroism spectroscopy, small-angle X-ray scattering, and transmission electron microscopy. In comparison with the native peptide sequence, it was found that the peptide secondary structure was stabilized against pH variation in the di- and tri-block copolymers with PEG. Small-angle X-ray scattering indicated the presence of fibrillar structures, the dimensions of which are comparable to the estimated width of a ?-strand (with terminal PEG chains in the case of the copolymers). Transmission electron microscopy on selectively stained and dried specimens shows directly the presence of fibrils. It is proposed that these fibrils result from the hierarchical self-assembly of peptide ?-strands into helical tapes, which then stack into fibrils. © 2005 American Chemical Society.

2005

Hybrid Polymer Foams for Osteochondral Tissue Engineering

Matthieu Cuénoud

Articular cartilage is a soft tissue that covers the ends of articulating bones, and is essential for maintaining joint motion, i.e. translation and rotation between the bones. Articular cartilage nevertheless has a limited capacity for self-repair, and cartilage lesions following traumatic injury may consequently initiate an irreversible degenerative process. This ultimately leads to progressive loss of joint function, pain and medical costs. Many different clinical treatments have been investigated, but these have not so far led to satisfactory long-term solutions. Tissue engineering research has therefore focused on the preparation of synthetic bioresorbable scaffolds that provide a template for cells and guide the process of tissue regeneration. In the present study, it is proposed to develop an osteochondral scaffold using novel solvent-free processing methods based on supercritical carbon dioxide (CO2) foaming. The approach is first to tailor the mechanical properties of medical grade polylactides (PLA), using poly(ethylene glycol) (PEG) as a plasticizer, to produce scaffolds with reduced elastic moduli intended for cartilage repair. These polymer scaffolds are then combined with an existing biocomposite scaffold (PLLA/bioceramic), developed for bone repair, to give a bilayered scaffold suitable for osteochondral repair. The investigation thus covers: (I) the preparation of plasticized polylactide and the dependence of its properties on composition; (II) the design of processing windows for the production of porous plasticized polylactide scaffolds by supercritical CO2 foaming; (III) the preparation of hybrid structures with gradients in composition and properties, and tailored interfaces; (IV)the properties and in vitro response of sterilized scaffolds. Plasticization of semicrystalline poly-L-lactide (PLLA) with PEG reduces Tg to below 37 °C, depending on the composition, implying the amorphous regions to be in the rubbery state at body temperature. While immersion in an aqueous medium tends to promote phase separation in blends containing low molar mass PEG, relatively good stability is observed with PEG with a molar mass of 35,000 g/mol. It has thus been possible to prepare interconnected, open-pore foams with porosities of more than 75 %, cell diameters in the range 200 to 700 pm and compression moduli of a few MPa. It was also observed that addition of PEG resulted in foams with increased pore diameters and lower foam densities than the neat polylactide, but also increased pore coalescence at high saturation pressures, effects that were accounted for by the large decrease in melt viscosity on addition of PEG. Furthermore, the compression moduli of the foams were shown to be strongly reduced on addition of PEG, which was assumed to be a direct consequence of the plasticization of the polylactide by PEG and the accompanying decrease in glass transition temperature, implying the amorphous content to be in the rubbery state at in vivo temperature, as required. Thus, foams with moduli ranging from 0.3 to 15 MPa could be prepared from the different PLA/PEG blends and copolymers studied. Bilayered scaffolds were produced by assembling the plasticized foams with a biocomposite foam using an adapted fusion bonding method. This allowed control of interfacial properties such as the bonding strength, and the interface density and permeability. These hybrid scaffolds exhibited well-defined layers with suitable properties for the repair of bone and cartilage, respectively. Finally, X-ray and y irradiation was shown to strongly degrade the polymer matrix. However, it was found that treatment with ethylene oxide gas could be used to sterilize the scaffolds without significantly modifying their properties, or compromising their biocompatibility, as borne out by in vitro tests. The approach proposed in this work was hence concluded to be highly promising for cartilage repair, and the resulting hybrid osteochondral scaffolds are ready for the next stage of the developmental work, which will consist of extended in vivo studies.