Stabilization of unilamellar catanionic vesicles induced by \u3b2-cyclodextrins: A strategy for a tunable drug delivery depot

The limited stability of catanionic vesicles has discouraged their wide use for encapsulation and controlled release of active substances. Their structure can easily break down to form lamellar phases, micelles or rearrange into multilamellar vesicles, as a consequence of small changes in their composition. However, despite the limited stability, catanionic vesicles possess an attractive architecture, which is able to efficiently encapsulate both hydrophobic and hydrophilic molecules. Therefore, improving the stability of the vesicles, as well as the control on unilamellar structures, are prerequisites for their wider application range. This study focuses on the impact of \u3b2-cyclodextrins for the stabilization of SDS/CTAB catanionic vesicles. Molar ratio and sample preparation procedures have been investigated to evaluate the temperature stability of catanionic vesicles. Diffusion and spectroscopic techniques evidenced that when \u3b2-cyclodextrins are added, unilamellar structures are stabilized above the multilamellar-unilamellar vesicles critical temperature. The results evidence encouraging perspectives for the use of vesicular nanoreservoirs for drug depot applications

A Multinuclear NMR Approach to the Study of the Lyotropic System CTAB-D20

CTAB-D2O liquid crystalline phase (CTAB = cetyltrimethylammonium bromide), type I according to magnetic anisotropy, has been investigated by means of 2H, 14N and 17O NMR at variable temperature. The residual quadrupolar splittings of ali these nuclei evidenced the alignment of the phase in the magnetic field. The interpretation of the data of D2O quadrupolar nuclei, commonly used in the Study of lyotropic liquid crystalline phases, is complicated because of water reorientation, exchange processes and variations of the hydration degree. The 14N quadrupolar splittings are much more reliable indicators of the orientation of surfactant aggregates since their interpretation in terms of the order parameter is straightforward in this case because the nitrogen nucleus is subject to an electric field gradient of axial symmetry and resides just in the head of the amphiphile

Functionalization of Enzymatically Synthesized Rigid Poly(itaconate)s via Post-Polymerization aza-Michael Addition of Primary Amines

8The bulky 1,4-cyclohexanedimethanol was used as co-monomer for introducing rigidity in lipase synthetized poly(itaconates). Poly(1,4-cyclohexanedimethanol itaconate) was synthetized on a 14 g scale at 50°C, under solvent-free conditions and 70 mbar using only 135 Units of lipase B from Candida antarctica per gram of monomer. The mild conditions preserved the labile vinyl group of itaconic acid and avoided the decomposition of 1,4-cyclohexanedimethanol observed in chemical polycondensation. Experimental and computational data show that the enzymatic polycondensation proceeds despite the low reactivity of C1 of itaconic acid. The rigid poly(1,4-cyclohexanedimethanol itaconate) was investigated in the context of aza-Michael addition of hexamethylenediamine and 2-phenylethylamine to the vinyl moiety. The enzymatically synthesized linear poly(1,4-butylene itaconate) was studied as a comparison. The two oligoesters (Molecular Weights ranging from 720 to 2859 g mol-1) reacted on a gram scale, at 40-50°C, at atmospheric pressure and in solvent-free conditions. The addition of primary amines led to amine-functionalized oligoesters but also to chain degradation, and the reactivity of the poly(itaconate)s was influenced by the rigidity of the polymer chain. Upon the formation of the secondary amine adduct, the linear poly(1,4-butylene itaconate) undergoes fast intramolecular cyclization and subsequent degradation via pyrrolidone formation, especially in the presence of hexamethylenediamine. On the contrary, the bulky 1,4-cyclohexanedimethanol confers rigidity to poly(1,4-cyclohexanedimethanol itaconate), which hampers the intramolecular cyclization. Also the bulkiness of the amine and the use of solvent emerged as factors that affect the reactivity of poly(itaconate)s. Therefore, the possibility to insert discrete units of itaconic acid in oligoesters using biocatalysts under solvent-free mild conditions opens new routes for the generation of bio-based functional polymers or amine-triggered degradable materials, as a function of the rigidity of the polyester chain.partially_openopenAlice Guarneri, Viola Cutifani, Marco Cespugli, Alessandro Pellis, Roberta Vassallo, Fioretta Asaro, Cynthia Ebert, Lucia GardossiGuarneri, Alice; Viola, Cutifani; Cespugli, Marco; Alessandro, Pellis; Roberta, Vassallo; Asaro, Fioretta; Ebert, Cynthia; Gardossi, Luci

Neuroprotective Properties of Cardoon Leaves Extracts against Neurodevelopmental Deficits in an In Vitro Model of Rett Syndrome Depend on the Extraction Method and Harvest Time

This study investigates the bioactive properties of different extracts of cardoon leaves in rescuing neuronal development arrest in an in vitro model of Rett syndrome (RTT). Samples were obtained from plants harvested at different maturity stages and extracted with two different method- ologies, namely Naviglio® and supercritical carbon dioxide (scCO2). While scCO2 extracts more hydrophobic fractions, the Naviglio® method extracts phenolic compounds and less hydrophobic components. Only the scCO2 cardoon leaves extract obtained from plants harvested in spring induced a significant rescue of neuronal atrophy in RTT neurons, while the scCO2 extract from the autumn harvest stimulated dendrite outgrowth in Wild-Type (WT) neurons. The scCO2 extracts were the richest in squalene, 3ß-taraxerol and lupeol, with concentrations in autumn harvest doubling those in spring harvest. The Naviglio® extract was rich in cynaropicrin and exerted a toxic effect at 20 μM on both WT and RTT neurons. When cynaropicrin, squalene, lupeol and 3ß-taraxerol were tested individually, no positive effect was observed, whereas a significant neurotoxicity of cynaropicrin and lupeol was evident. In conclusion, cardoon leaves extracts with high content of hydrophobic bioactive molecules and low cynaropicrin and lupeol concentrations have pharmacological potential to stimulate neuronal development in RTT and WT neurons in vitro

Nucleation, reorganization and disassembly of an active network from lactose-modified chitosan mimicking biological matrices

Developing synthetic materials able to mimic micro- and macrorheological properties of natural networks opens up to novel applications and concepts in materials science. The present contribution describes an active network based on a semi-synthetic polymer, a lactitol-bearing chitosan derivative (Chitlac), and a transient inorganic cross-linker, boric acid. Due to the many and diverse anchoring points for boric acid on the flanking groups of Chitlac, the cross-links constantly break and reform in a highly dynamic fashion. The consequence is a network with unusual non-equilibrium and mechanical properties closely resembling the rheological behavior of natural three-dimensional arrangements and of cytoskeleton. Concepts like network nucleation, reorganization and disassembly are declined in terms of amount of the cross-linker, which acts as a putative motor for remodeling of the network upon application of energy. The out-of-equilibrium and non-linear behavior render the semi-synthetic system of great interest for tissue engineering and for developing in-vitro mimics of natural active matrices

Understanding Marine Biodegradation of Bio-Based Oligoesters and Plasticizers

The study reports the enzymatic synthesis of bio-based oligoesters and chemo-enzymatic processes for obtaining epoxidized bioplasticizers and biolubricants starting from cardoon seed oil. All of the molecules had MW below 1000 g mol-1 and were analyzed in terms of marine biodegradation. The data shed light on the effects of the chemical structure, chemical bond lability, thermal behavior, and water solubility on biodegradation. Moreover, the analysis of the biodegradation of the building blocks that constituted the different bio-based products allowed us to distinguish between different chemical and physicochemical factors. These hints are of major importance for the rational eco-design of new benign bio-based products. Overall, the high lability of ester bonds was confirmed, along with the negligible effect of the presence of epoxy rings on triglyceride structures. The biodegradation data clearly indicated that the monomers/building blocks undergo a much slower process of abiotic or biotic transformations, potentially leading to accumulation. Therefore, the simple analysis of the erosion, hydrolysis, or visual/chemical disappearance of the chemical products or plastic is not sufficient, but ecotoxicity studies on the effects of such small molecules are of major importance. The use of natural feedstocks, such as vegetable seed oils and their derivatives, allows the minimization of these risks, because microorganisms have evolved enzymes and metabolic pathways for processing such natural molecules

Soluble HLA-G expression levels and HLA-G/irinotecan association in metastatic colorectal cancer treated with irinotecan-based strategy

We here explore the soluble Human Leukocyte Antigen-G (sHLA-G) expression level as clinical biomarker in metastatic colorectal cancer (mCRC). To this aim the sHLA-G protein was measured in plasma samples of 40 patients with mCRC treated with the FOLFIRI (irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and leucovorin (LV)) regimen. The results suggest a link between HLA-G levels and irinotecan (CPT-11) pharmacokinetic, leading to hypothesize a molecular interaction between sHLA-G and CPT-11. This interaction was confirmed experimentally by fluorescence spectroscopy. HLA-G is known to exist in a number of polymorphs that affect both the protein expression levels and its peptide-binding cleft. The interaction between HLA-G polymorphs and CPT-11 was explored by means of computational modelling, confirming the hypothesis that CPT-11 could actually target the peptide binding cleft of the most common HLA-G polymorphs

An Efficient Synthesis of Chiral Non\u2010Racemic Hydroxyalkanoic Acids by Olefin Cross\u2010Metathesis Reactions

Cross-metathesis reactions of 1-hepten-3-ol, 1-octen-4-ol, 1-octen-4-yl acetate and 1-tetradecen-4-ol with unsaturated methyl esters were investigated to optimize the synthesis of methyl hydroxyalkenoates, precursors of hydroxyalkanoic acids. Various commercially available catalysts, concentration ratios of reagents as well as microwave irradiation were explored. (R)-8-hydroxydodecanoic acid and (S)-8-hydroxystearic acid were successfully obtained in 3 steps from enantiomerically enriched alcohols

Azelaic Acid: A Bio-Based Building Block for Biodegradable Polymers

The production of fine chemicals, new materials and products from renewable feedstocks represents a continuous challenge. Several procedures have been reported in the literature or patented in the last decade for the main biomass components: carbohydrates (75%), lignins (20%), fats and oils (5%) [1]. Regarding oleochemical developments, the oxidative cleavage of unsaturated fatty acids to produce dicarboxylic acids, hydroxy acids, and amino acids has received great attention in the last decade [2]. Two main oleochemical products obtained by the cleavage of unsaturated fatty acids are sebacic acid and azelaic acid. Azelaic acid (AzA) is a naturally occurring saturated nine carbon atom dicarboxylic acid found in whole grains, wheat, rye and barley [2], first detected in rancid fats. It can be formed endogenously from substrates such as longer-chain dicarboxylic acids and processes like the metabolism of oleic acid, and ψ-oxidation of monocarboxylic acids. The azelaic acid market is predicted to reach USD 160 million by 2023 and the applications include pharmacological ingredients, polymers, plastics, lubricants and materials for electronics [3]. The aim of the present review is to highlight the potential of azelaic acid as powerful building block for the synthesis of bio-based and biodegradable polymers, with a special emphasis on the green synthetic routes, embracing both chemical and enzymatic methods

Turning biomass into functional composite materials: rice husk for fully renewable immobilized biocatalysts

Rice husk is an underexploited, low density and highly robust composite material, massively available from rice processing. Here we report two new procedures for the formulation of immobilized lipases applicable in fats and oils transformations. The enzymes were covalently anchored on aldehyde groups introduced on rice husk by laccase-catalysed oxidation of the cellulose component. The method avoids the use of toxic glutaraldehyde while allows for the application and recycling of the biocatalysts in aqueous media. The second method used a fluidized bed granulator for the coating of the particles of rice husk (200\u2013400 m) in the presence of water-soluble binders. The formulations are mechanically stable and suitable for applications in different hydrophobic media. Both methods allow for the recovery and reuse of the rice husk at the end of the life cycle of the biocatalysts