Thermoplastic Cellulose-Based Compound for Additive Manufacturing.

The increasing environmental awareness is driving towards novel sustainable high-performance materials applicable for future manufacturing technologies like additive manufacturing (AM). Cellulose is abundantly available renewable and sustainable raw material. This work focused on studying the properties of thermoplastic cellulose-based composites and their properties using injection molding and 3D printing of granules. The aim was to maximize the cellulose content in composites. Different compounds were prepared using cellulose acetate propionate (CAP) and commercial cellulose acetate propionate with plasticizer (CP) as polymer matrices, microcellulose (mc) and novel cellulose-ester additives; cellulose octanoate (C8) and cellulose palmitate (C16). The performance of compounds was compared to a commercial poly(lactic acid)-based cellulose fiber containing composite. As a result, CP-based compounds had tensile and Charpy impact strength properties comparable to commercial reference, but lower modulus. CP-compounds showed glass transition temperature (Tg) over 58% and heat distortion temperature (HDT) 12% higher compared to reference. CAP with C16 had HDT 82.1 °C. All the compounds were 3D printable using granular printing, but CAP compounds had challenges with printed layer adhesion. This study shows the potential to tailor thermoplastic cellulose-based composite materials, although more research is needed before obtaining all-cellulose 3D printable composite material with high-performance.

High-Generation Amphiphilic Janus-Dendrimers as Stabilizing Agents for Drug Suspensions.

Pharmaceutical nanosuspensions are formed when drug crystals are suspended in aqueous media in the presence of stabilizers. This technology offers a convenient way to enhance the dissolution of poorly water-soluble drug compounds. The stabilizers exert their action through electrostatic or steric interactions, however, the molecular requirements of stabilizing agents have not been studied extensively. Here, four structurally related amphiphilic Janus-dendrimers were synthesized and screened to determine the roles of different macromolecular domains on the stabilization of drug crystals. Physical interaction and nanomilling experiments have substantiated that Janus-dendrimers with fourth generation hydrophilic dendrons were superior to third generation analogues and Poloxamer 188 in stabilizing indomethacin suspensions. Contact angle and surface plasmon resonance measurements support the hypothesis that Janus-dendrimers bind to indomethacin surfaces via hydrophobic interactions and that the number of hydrophobic alkyl tails determines the adsorption kinetics of the Janus-dendrimers. The results showed that amphiphilic Janus-dendrimers adsorb onto drug particles and thus can be used to provide steric stabilization against aggregation and recrystallization. The modular synthetic route for new amphiphilic Janus-dendrimers offers, thus, for the first time a versatile platform for stable general-use stabilizing agents of drug suspensions.

Self-assembly of amphiphilic Janus dendrimers into mechanically robust supramolecular hydrogels for sustained drug release.

Compounds that can gelate aqueous solutions offer an intriguing toolbox to create functional hydrogel materials for biomedical applications. Amphiphilic Janus dendrimers with low molecular weights can readily form self-assembled fibers at very low mass proportion (0.2 wt %) to create supramolecular hydrogels (G'≫G'') with outstanding mechanical properties and storage modulus of G'>1000 Pa. The G' value and gel melting temperature can be tuned by modulating the position or number of hydrophobic alkyl chains in the dendrimer structure; thus enabling exquisite control over the mesoscale material properties in these molecular assemblies. The gels are formed within seconds by simple injection of ethanol-solvated dendrimers into an aqueous solution. Cryogenic TEM, small-angle X-ray scattering, and SEM were used to confirm the fibrous structure morphology of the gels. Furthermore, the gels can be efficiently loaded with different bioactive cargo, such as active enzymes, peptides, or small-molecule drugs, to be used for sustained release in drug delivery.

Templating gold surfaces with function: a self-assembled dendritic monolayer methodology based on monodisperse polyester scaffolds.

The antibiotic resistance developed among several pathogenic bacterial strains has spurred interest in understanding bacterial adhesion down to a molecular level. Consequently, analytical methods that rely on bioactive and multivalent sensor surfaces are sought to detect and suppress infections. To deliver functional sensor surfaces with an optimized degree of molecular packaging, we explore a library of compact and monodisperse dendritic scaffolds based on the nontoxic 2,2-bis(methylol)propionic acid (bis-MPA). A self-assembled dendritic monolayer (SADM) methodology to gold surfaces capitalizes on the design of aqueous soluble dendritic structures that bear sulfur-containing core functionalities. The nature of sulfur (either disulfide or thiol), the size of the dendritic framework (generation 1-3), the distance between the sulfur and the dendritic wedge (4 or 14 Å), and the type of functional end group (hydroxyl or mannose) were key structural elements that were identified to affect the packaging densities assembled on the surfaces. Both surface plasmon resonance (SPR) and resonance-enhanced surface impedance (RESI) experiments revealed rapid formation of homogenously covered SADMs on gold surfaces. The array of dendritic structures enabled the fabrication of functional gold surfaces displaying molecular covering densities of 0.33-2.2 molecules·nm(-2) and functional availability of 0.95-5.5 groups·nm(-2). The cell scavenging ability of these sensor surfaces for Escherichia coli MS7fim+ bacteria revealed 2.5 times enhanced recognition for G3-mannosylated surfaces when compared to G3-hydroxylated SADM surfaces. This promising methodology delivers functional gold sensor surfaces and represents a facile route for probing surface interactions between multivalently presented motifs and cells in a controlled surface setting.

Bifunctional dendronized cellulose surfaces as biosensors.

Well-defined dendronized cellulose substrates displaying multiple representations of dual-functionality were constructed by taking advantage of the efficiency of the click reaction combined with traditional anhydride chemistry. First, activated cellulose surfaces were decorated with several generations of dendrons, and their peripheral reactive groups were subsequently reacted with a trifunctional orthogonal monomer. The generated substrate tool box was successfully explored by accurately tuning the surface function using a versatile orthogonal dual postfunctionalization approach. In general, the reactions were monitored by using a click-dye reagent or a quartz crystal microbalance (QCM) technique, and the resulting surfaces were well-characterized using XPS, FT-IR, and contact angle measurements. Utilizing this approach two different surfaces have been obtained; that is, triethylenglycol oligomers and amoxicillin molecules were efficiently introduced to the dendritic surface. As a second example, mannose-decorated hydroxyl functional surfaces illustrated their potential as biosensors by multivalent detection of lectin protein at concentration as low as 5 nM.

Foamability of Cellulose Palmitate Using Various Physical Blowing Agents in the Extrusion Process.

Polymer foams are widely used in several fields such as thermal insulation, acoustics, automotive, and packaging. The most widely used polymer foams are made of polyurethane, polystyrene, and polyethylene but environmental awareness is boosting interest towards alternative bio-based materials. In this study, the suitability of bio-based thermoplastic cellulose palmitate for extrusion foaming was studied. Isobutane, carbon dioxide (CO2), and nitrogen (N2) were tested as blowing agents in different concentrations. Each of them enabled cellulose palmitate foam formation. Isobutane foams exhibited the lowest density with the largest average cell size and nitrogen foams indicated most uniform cell morphology. The effect of die temperature on foamability was further studied with isobutane (3 wt%) as a blowing agent. Die temperature had a relatively low impact on foam density and the differences were mainly encountered with regard to surface quality and cell size distribution. This study demonstrates that cellulose palmitate can be foamed but to produce foams with greater quality, the material homogeneity needs to be improved and researched further.

Evaluation of esterification routes for long chain cellulose esters.

Long chain cellulose esters are internally plasticized bio-based materials, which have good future potential in several applications such as coatings, films and plastics. The long chain cellulose esters with different side chain lengths were synthesized using different esterification methods. When homogeneous esterification was used, the acyl chloride method was the most effective esterification method and cellulose esters prepared using this method have the highest degree of substitution values (DS). In this case, the long chain cellulose esters showed DS values from 0.3 to 1.3 depending on the side chain length of cellulose esters. CDI activation, vinyl transesterification and anhydride routes resulted in somewhat lower DS values. The cellulose was also pretreated with ozone, which decreased cellulose molar mass, and resulted in synthesized cellulose esters having higher DS and better reaction efficiency than untreated cellulose. When heterogeneous esterifications were used, only acyl chloride method seemed to work.

Large neutral amino acid transporter enables brain drug delivery via prodrugs.

The blood-brain barrier efficiently controls the entry of drug molecules into the brain. We describe a feasible means to achieve carrier-mediated drug transport into the rat brain via the specific, large neutral amino acid transporter (LAT1) by conjugating a model compound to L-tyrosine. A hydrophilic drug, ketoprofen, that is not a substrate for LAT1 was chosen as a model compound. The mechanism and the kinetics of the brain uptake of the prodrug were determined with an in situ rat brain perfusion technique. The brain uptake of the prodrug was found to be concentration-dependent. In addition, a specific LAT1 inhibitor significantly decreased the brain uptake of the prodrug. Therefore, our results reveal for the first time that a drug-substrate conjugate is able to transport drugs into the brain via LAT1.

Injection Molding of Thermoplastic Cellulose Esters and Their Compatibility with Poly(Lactic Acid) and Polyethylene.

Interest in biobased polymers from renewable resources has grown in recent years due to environmental concerns, but they still have a minimal fraction of the total global market. In this study, the injection molding of thermoplastic cellulose octanate (cellulose C8) and cellulose palmitate (cellulose C16) were studied. The mechanical properties of injection-molded test specimens were analyzed by using tensile testing, and the internal structure of injection-molded objects was studied by using a field emission scanning electron microscopy (FE-SEM). We showed that thermoplastic cellulose C8 and cellulose C16 were completely processable without the addition of a plasticizer, which is very unusual in the case of cellulose esters. The compatibility of cellulose esters with poly(lactic acid) (PLA) and biopolyethylene (bio-PE) was also tested. By compounding the cellulose esters with PLA, the elongation of PLA-based blends could be improved and the density could be reduced. The tested thermoplastic cellulose materials were fully biobased, and have good future potential to be used in injection molding applications.

The effect of oxyalkylation and application of polymer dispersions on the thermoformability and extensibility of paper.

Wood fiber-based packaging materials, as renewable materials, have growing market potential due to their sustainability. A new breakthrough in cellulose-based packaging requires some improvement in the mechanical properties of paper. Bleached softwood kraft pulp was mechanically treated, in two stages, using high- and low-consistency refining, sequentially. Chemical treatment of pulp using the oxyalkylation method was applied to modify a portion of fiber material, especially the fiber surface, and its compatibility with polymer dispersions including one carbohydrate polymer. The results showed that the compatibility of the cellulosic fibers with some polymers could be improved with oxyalkylation. By adjusting mechanical and chemical treatments, and the thermoforming conditions, the formability of paper was improved, but simultaneously the strength and stiffness decreased. The results suggest that the formability of the paper is not a direct function of the extensibility of the applied polymer, but also depends on the fiber network structure and surface energy.

Polymerization of coniferyl alcohol by Mn3+ -mediated (enzymatic) oxidation: Effects of H2 O2 concentration, aqueous organic solvents, and pH.

The objective of this study was to evaluate the ability of one versatile peroxidase and the biocatalytically generated complex Mn(III)-malonate to polymerize coniferyl alcohol (CA) to obtain dehydrogenation polymers (DHPs) and to characterize how closely the structures of the formed DHPs resemble native lignin. Hydrogen peroxide was used as oxidant and Mn2+ as mediator. Based on the yields of the polymerized product, it was concluded that the enzymatic reaction should be performed in aqueous solution without organic solvents at 4.5 ≤ pH ≤ 6.0 and with 0.75 ≤ H2 O2 :CA ratio ≤ 1. The results obtained from the Mn3+ -malonate-mediated polymerization showed that the yield was almost 100%. Reaction conditions had, however, effect on the structures of the formed DHPs, as detected by size exclusion chromatography and pyrolysis-GC/MS. It can be concluded that from the structural point of view, the optimal pH for DHP formation using the presently studied system was 3 or 4.5. Low H2 O2 /CA ratio was beneficial to avoid oxidative side reactions. However, the high frequency of ß-ß linkages in all cases points to dimer formation between monomeric CA rather than endwise polymerization. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:81-90, 2018.

Hydrophobization and smoothing of cellulose nanofibril films by cellulose ester coatings.

The Cellulose nanofibrils (CNF), also referred to as nanocellulose, is one of the most studied bio-based material in recent year, which has good potential in the future for packaging applications due to its excellent mechanical strength and oxygen barrier properties. In the future, CNF films may also find new applications for example in printed electronics, if the surface smoothness of CNF films can be improved. One way to improve surface smoothness is to use thin coating solutions with zero porosity, such as molar mass controlled cellulose ester coatings. In this study, we have coated CNF films using molar mass controlled cellulose esters with different side chain lengths forming 3-layer film (ester-CNF-ester). These coatings improved significantly the smoothness of CNF films. The 3-layer films have also good water vapor barrier and mechanical properties and the films are heat-sealable, which enable various new applications in the future.

Modular synthesis of self-assembling Janus-dendrimers and facile preparation of drug-loaded dendrimersomes.

Materials and methods aimed at the next generation of nanoscale carriers for drugs and other therapeutics are currently in great demand. Yet, creating these precise molecular arrangements in a feasible and straightforward manner represents a remarkable challenge. Herein we report a modular synthetic route for amphiphilic Janus-dendrimers via a copper-catalyzed click reaction (CuAAC) and a facile procedure, using simple injection, to obtain highly uniform dendrimersomes with efficient loading of the model drug compound propranolol. The resulting assemblies were analyzed by dynamic light scattering and cryogenic transmission electron microscopy revealing the formation of unilamellar and multilamellar dendrimersomes. The formation of a bilayer structure was confirmed using cryo-TEM and confocal microscopy visualization of an encapsulated solvatochromic dye (Nile Red). The dendrimersomes reported here are tunable in size, stable over time and display robust thermal stability in aqueous media. Our results expand the scope of dendrimer-based supramolecular colloidal systems and offer the means for one-step fabrication of drug-loaded dendrimersomes in the size range of 90-200 nm, ideal for biomedical applications.

The effect of cellulose molar mass on the properties of palmitate esters.

Nowadays one of the growing trends is to replace oil-based products with cellulose-based materials. Currently most cellulose esters require a huge excess of chemicals and have therefore, not been broadly used in the industry. Here, we show that decreasing the molar mass of cellulose by ozone hydrolysis provides cellulose functionalization with less chemical consumption. To reveal the differences in reactivity and chemical consumption, we showed esterification of both native cellulose and ozone treated hydrolyzed cellulose. Based on the results, the molar mass of the starting cellulose has a significant effect on the end product's degree of substitution and properties. Furthermore, molar mass controlled palmitate esters form mechanically strong, flexible and optically transparent films with excellent water barrier properties. We anticipate that molar mass controlled cellulose will provide a starting point for the greater use of cellulose based materials, in various application, such as films and composites.

Bisfunctionalized Janus molecules.

[reaction: see text] Bisfunctionalized dendritic multiester molecules were synthesized by combined protection-deprotection and divergent-convergent-divergent sequences in high yields leading to dendritic molecules that combine two functionally different surfaces, polar aliphatic arborol and nonpolar gallate ether moieties, resulting in a two-faced Janus molecule.

Brain uptake of ketoprofen-lysine prodrug in rats.

The blood-brain barrier (BBB) controls the entry of xenobiotics into the brain. Often the development of central nervous system drugs needs to be terminated because of their poor brain uptake. We describe a way to achieve large neutral amino acid transporter (LAT1)-mediated drug transport into the rat brain. We conjugated ketoprofen to an amino acid l-lysine so that the prodrug could access LAT1. The LAT1-mediated brain uptake of the prodrug was demonstrated with in situ rat brain perfusion technique. The ability of the prodrug to deliver ketoprofen into the site of action, the brain intracellular fluid, was determined combining in vivo and in vitro experiments. A rapid brain uptake from blood and cell uptake was seen both in in situ and in vivo experiments. Therefore, our results show that a prodrug approach can achieve uptake of drugs via LAT1 into the brain intracellular fluid. The distribution of the prodrug in the brain parenchyma and the site of parent drug release in the brain were shown with in vivo and in vitro studies. In addition, our results show that although lysine or ketoprofen are not LAT1-substrates themselves, by combining these molecules, the formed prodrug has affinity for LAT1.

Self-assembly of Janus dendrimers into uniform dendrimersomes and other complex architectures.

Self-assembled nanostructures obtained from natural and synthetic amphiphiles serve as mimics of biological membranes and enable the delivery of drugs, proteins, genes, and imaging agents. Yet the precise molecular arrangements demanded by these functions are difficult to achieve. Libraries of amphiphilic Janus dendrimers, prepared by facile coupling of tailored hydrophilic and hydrophobic branched segments, have been screened by cryogenic transmission electron microscopy, revealing a rich palette of morphologies in water, including vesicles, denoted dendrimersomes, cubosomes, disks, tubular vesicles, and helical ribbons. Dendrimersomes marry the stability and mechanical strength obtainable from polymersomes with the biological function of stabilized phospholipid liposomes, plus superior uniformity of size, ease of formation, and chemical functionalization. This modular synthesis strategy provides access to systematic tuning of molecular structure and of self-assembled architecture.

Glucose promoiety enables glucose transporter mediated brain uptake of ketoprofen and indomethacin prodrugs in rats.

The brain uptake of solutes is efficiently governed by the blood-brain barrier (BBB). The BBB expresses a number of carrier-mediated transport mechanisms, and new knowledge of these BBB transporters can be used in the rational targeted delivery of drug molecules for active transport. One attractive approach is to conjugate an endogenous transporter substrate to the active drug molecule to utilize the prodrug approach. In the present study, ketoprofen and indomethacin were conjugated with glucose and the brain uptake mechanism of the prodrugs was determined with the in situ rat brain perfusion technique. Two of the prodrugs were able to significantly inhibit the uptake of glucose transporter (GluT1)-mediated uptake of glucose, thereby demonstrating affinity to the transporter. Furthermore, the prodrugs were able to cross the BBB in a temperature-dependent manner, suggesting that the brain uptake of the prodrugs is carrier-mediated.