Papers by Fabrizio Caldera
Tuning structural parameters for the optimization of drug delivery performance of cyclodextrin-based nanosponges
Expert Opinion on Drug Delivery, 2016
In light of the recent development of new soft materials, nanostructured self-assembled systems h... more In light of the recent development of new soft materials, nanostructured self-assembled systems have attracted attention in a variety of technological fields of high social impact. Cyclodextrin nanosponges (CDNS) represent a new and highly versatile class of cross-linked cyclodextrin (CD)-based nanoporous polymers. Their intriguing properties, including safety, biodegradability, negligible toxicity, marked swelling behavior, superior inclusion capability with respect to native CD, are the bases for potential for applications in drug delivery, tissue engineering and regenerative medicine. We report on the state-of-art concerning a detailed characterization of structural and dynamical features of CDNS explored by the combined use of different and complementary techniques, such as Fourier transform infrared absorption in attenuated total reflectance geometry (FTIR-ATR) and Raman spectroscopies, and high resolution magic angle spinning (HR-MAS) NMR spectroscopy. The ambitious objective is to furnish an exhaustive survey of the role played by hydrophobic and hydrophilic groups within the cross-linked network, in dry and swollen states, in determining the macroscopic functional features of CDNS. The reported results may significantly contribute in the rational design and optimization of new stimuli-responsive systems exhibiting tunable inclusion/release properties, adapted to the therapeutic demands of pathology.
Corrigendum to “Preparation of functionalized cotton fabrics by means of melatonin loaded β-cyclodextrin nanosponges” [Carbohydrate Polymers (2016) 24–30]
Carbohydrate Polymers, 2016
Preparation of Functionalized Cotton Fabrics by Means of Melatonin Loaded Β-Cyclodextrin Nanosponges
Carbohydrate Polymers, 2016
Biofunctional textiles are a new category of advanced materials which combine conventional textil... more Biofunctional textiles are a new category of advanced materials which combine conventional textiles with advanced drug delivery systems to obtain fabrics able to release active principles through skin. The work presents the synthesis of hyper cross-linked β-cyclodextrins nanosponges with the carbonyl group acting as bridge between cyclodextrin molecules. The result of the synthesis is a 3-D porous structure, where melatonin molecules have been complexed. The complex has been characterized by elemental analysis, DSC, SEM, XRD and FT-IR spectroscopy and the results confirm that melatonin interacts with the synthesized nanosponge at molecular level. Melatonin loaded nanosponges have been dispersed on cotton fibres, which have proved to be a suitable substrate for durable nanosponge adsorption. The in vitro release tests from the funtionalized fabrics have shown a zero order kinetics, which is typical of a reservoir diffusion controlled system.
Glutathione Bioresponsive Cyclodextrin Nanosponges
ChemPlusChem, 2015
Solvent- and phase-controlled photochirogenesis. Enantiodifferentiating photoisomerization of (Z)-cyclooctene sensitized by cyclic nigerosylnigerose-based nanosponges crosslinked by pyromellitate
Organic & biomolecular chemistry, Jan 24, 2015
Cyclic nigerosylnigerose (CNN), a saucer-shaped cyclic tetrasaccharide with a shallow concave sur... more Cyclic nigerosylnigerose (CNN), a saucer-shaped cyclic tetrasaccharide with a shallow concave surface, was reacted with pyromellitic dianhydride in 1 : 2 and 1 : 4 ratios to give two CNN-based polymers of different degrees of crosslinking, both of which swelled upon soaking in water, acting as a 'nanosponge' (NS). These NSs evolved several phases from isotropic solution to flowing and rigid gels via suspension by gradually increasing the concentration in water. The CNN-NSs thus prepared effectively mediated the enantiodifferentiating photoisomerization of (Z)-cyclooctene () to chiral (E)-isomer (). The enantiomeric excess (ee) of obtained was a critical function of the solvent composition and the phase evolved at different CNN-NS concentrations in water. In isotropic solution, the enantioselectivity was generally low (-4% to +6% ee) but the chiral sense of was inverted by increasing the methanol content. Interestingly, the product's ee was controlled more dramatically by...
Membranes, 2012
Although the roots of molecularly imprinted polymers lie in the beginning of 1930s in the past ce... more Although the roots of molecularly imprinted polymers lie in the beginning of 1930s in the past century, they have had an exponential growth only 40-50 years later by the works of Wulff and especially by Mosbach. More recently, it was also proved that molecular imprinted membranes (i.e., polymer thin films) that show recognition properties at molecular level of the template molecule are used in their formation. Different procedures and potential application in separation processes and catalysis are reported. The influences of different parameters on the discrimination abilities are also discussed.
Heritage Science, 2015
Poly(vinylacohol) (PVA) is a versatile polymer capable of forming hydrogels useful in a wide rang... more Poly(vinylacohol) (PVA) is a versatile polymer capable of forming hydrogels useful in a wide range of applications. Hydrogels based on cross-linking of PVA with borax, and able to incorporate organic solvents, have been used in the field of cultural heritage as tool for cleaning the surfaces. Poly(ethylenoxide) (PEO) has been introduced in the formulations of PVA-borax, with the aim of increasing the gel compatibility with organic solvents and of improving the mechanical properties of the materials. The formulations were investigated with rheological characterization, solvent loss measurements and study of the free water through the determination of the Free Water Index. The PEO molecules do not participate in the formation of the network but have been found to be responsible for a decrement of the storage moduli, explained by a spacing between crosslinks and the partial disentanglement of the PVA chains. At the same time PEO produces in the gel an increase of the apparent relaxation time, thus stabilizing the dispersions and enhancing their ability to maintain the shape. Cleaning tests for removal of an acrylic coating on limestone have been also successfully performed.
Acute and Repeated Dose Toxicity Studies of Different β-Cyclodextrin-Based Nanosponge Formulations
Journal of Pharmaceutical Sciences, 2015
Nanosponges (NS) show promising results in different fields such as medicine, agriculture, water ... more Nanosponges (NS) show promising results in different fields such as medicine, agriculture, water purification, fire engineering and so on. The present study was designed to evaluate toxicity of different NS formulations (namely, S1-S6) synthesized with different cross-linking agents such as carbonyl diimidazole, pyromellitic dianhydride and hexamethylene diisocynate; and preparation methods in experimental animals. Acute and repeated dose toxicity studies of formulations were carried out as per OECD guidelines 423 and 407, respectively. For acute toxicity study, formulations were administered to female rats at doses of 300 and 2000 mg/kg orally. The general behaviour of the rats was continuously monitored for 1 h after dosing, periodically during the first 24 h and daily thereafter for a total of 14 days. On day 14, animals were fasted overnight, weighed, and sacrificed. After sacrification, animals were subjected to necropsy. For repeated dose toxicity study, rats of either sex were orally administered with formulations at the dose of 300 mg/kg per day for a period of 28 days. The maximally tolerated dose of all formulations was found to be 2000 mg/kg. Repeated administration of formulations for 28 days did not show any significant changes in haematological and biochemical parameters in experimental animals. These results indicate that the formulations are safe, when tested in experimental animals. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
Peroxidase-encapsulated cyclodextrin nanosponge immunoconjugates as a signal enhancement tool in optical and electrochemical assays
The Analyst, Jan 21, 2014
Cyclodextrin nanosponges bearing carboxylate groups have been prepared by crosslinking β-cyclodex... more Cyclodextrin nanosponges bearing carboxylate groups have been prepared by crosslinking β-cyclodextrin with pyromellitic dianhydride to form a carboxylic acid terminated nanoporous material. The surface of the particles was covalently modified with an anti-IgG antibody and then loaded with horseradish peroxidase. The structures of unmodified and protein modified nanosponge particles were investigated by Raman spectroscopy and imaging methods. Confocal microscopy indicates that the antibody is located in the outside of the particle while HRP is encapsulated in the inner part. The possibility to use these modified nanosponges as a signal enhancement tool in enzyme-linked colorimetric and electrochemical assays was evaluated using a sandwich format comprising immobilised gliadin as an antigen, a target anti-gliadin antibody and an anti-IgG antibody conjugated to the enzyme-loaded nanosponge immunoconjugates.
The application of nanosponges to cancer drug delivery
Expert opinion on drug delivery, 2014
The design of new nanocarriers as a strategy for the delivery of anti-cancer drugs offers a poten... more The design of new nanocarriers as a strategy for the delivery of anti-cancer drugs offers a potential platform to overcome some limitations of current clinical treatments and to achieve targeted release into tumour tissues. Cyclodextrin-based nanosponges are a novel nanosized delivery system composed of hyper-cross-linked cyclodextrins connected in a three-dimensional network. They form porous nanoparticles with sizes lower than 500 nm, spherical shape and negative surface charge. They show a good capacity for incorporating small molecules, macromolecules, ions and gases within their structure. This review will describe some applications of cyclodextrin-based nanosponges as carriers for anticancer drugs. Recent smart nanosponges, able to be responsive to an external stimulus, will be also discussed. In vitro and in vivo experimental results, obtained with currently used molecules, such as paclitaxel, doxorubicin, 5-fluorourcil and tamoxifen, will be shown. Cyclodextrin-based nanospo...
Novel cyclodextrin nanosponges for delivery of calcium in hyperphosphatemia
International journal of pharmaceutics, 2013
Cyclodextrin nanosponges are solid, porous nanoparticulate three dimensional structures, have bee... more Cyclodextrin nanosponges are solid, porous nanoparticulate three dimensional structures, have been used as delivery system of different drugs. In this work, new cyclodextrin-based nanosponges of calcium carbonate were prepared by polymer condensation method to release the calcium in controlled manner in the treatment of hyperphosphatemia as novel carriers. SEM measurements revealed their roughly spherical shape, porous nature and mean particle size of about 400 nm. Zeta potentials of the nanosponges were sufficiently high to obtain stable formulations. The encapsulation efficiencies of calcium in nanosponge formulations were found to be 81-95%. The moisture contents of the nanosponges were in the range of 0.1-0.7%. The optimized formulation produces enteric and controlled release kinetics of calcium in the management and treatment of hyperphosphatemia. It was also observed that calcium ions bound efficiently to free phosphate in a pH-dependent fashion especially at pH 7. In accelera...
β-Cyclodextrin Nanosponges as Multifunctional Ingredient in Water-Containing Semisolid Formulations for Skin Delivery
Journal of Pharmaceutical Sciences, 2014
A β-cyclodextrin nanosponge cross-linked with pyromellitic dianhydride (βNS-PYRO) is reported for... more A β-cyclodextrin nanosponge cross-linked with pyromellitic dianhydride (βNS-PYRO) is reported for the first time as multifunctional ingredient in semisolid formulations for drug delivery to the skin. The role of βNS-PYRO on solubilization and stabilization of the photosensitizer benzoporphyrin-derivative monoacid ring A (BPDMA) and all-trans retinoic acid (atRA) as well as its effect on skin permeation of diclofenac (DIC) was investigated. Aqueous solutions, gels, and cream-gels were prepared from mixtures of βNS-PYRO with a conventional gelling agent at specific ratios. The incorporation of BPDMA in βNS-PYRO water solutions prevented its aggregation and gave kinetically stable complexes with high photostability and singlet oxygen generation upon irradiation. atRA incorporated in the βNS-PYRO-containing gel demonstrated a remarkable stability as compared with the formulation without βNS-PYRO, resulting in an eightfold increase of its lifetime. Skin permeation studies highlighted that βNS-PYRO in gels and cream-gels containing DIC significantly decreased the amount of drug permeated through the skin while increasing its amount in stratum corneum and viable epidermis. Overall, swellable βNS-PYRO turns to be a multifunctional coingredient with potential in topical monophasic and biphasic formulations to stabilize light-sensitive drugs and to localize the action of highly penetrating drugs in the external layers of skin.
Materials Chemistry and Physics, 2011
Mixed micellar systems containing polystyrene-block-poly(ethylene oxide) (PS-b-PEO) diblock copol... more Mixed micellar systems containing polystyrene-block-poly(ethylene oxide) (PS-b-PEO) diblock copolymers and TiO 2 nanoparticles in a solvent/non-solvent pair were prepared and used as scaffolds in order to obtain nanostructured titania films. The inorganic content was varied in a wide range of compositions, focusing on micellar systems with PS cores and PEO/TiO 2 coronas. The spherical-to-cylindrical micelle transition was achieved by adding a small amount of homopolymer of the same nature of the core-forming block. Thin PS-b-PEO/TiO 2 hybrid films with different morphologies were prepared by spin coating micellar solutions and were transformed into the corresponding titania films by thermal treatments. The degradation of the polymer template and the simultaneous crystallization of titanium dioxide were carried out without collapsing of the nanostructures. As a final result porous and worm-like nanostructured titania films were obtained.
Encapsulation of apple polyphenols in β-CD nanosponges
Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2014
ABSTRACT Rutin, phloridzin and chlorogenic acid are some of the most important and characteristic... more ABSTRACT Rutin, phloridzin and chlorogenic acid are some of the most important and characteristic polyphenols found in apples and their by-products (cider, apple juice, apple pomace, etc.). Despite their antioxidant power, their low stability under light or heating conditions restricts the use of this kind of molecules as nutraceuticals. To deal with this issue, encapsulation seems to be an alternative solution. Based on the obtained results, it can be concluded that β-cyclodextrin nanosponges (β-CD NS) are promising agents for the encapsulation of polyphenols. Rutin, phloridzin and chlorogenic acid have been included for the first time in β-CD NS in this work. In particular, the highest encapsulation efficiency for rutin (83.7 %) was obtained using 1,1′-carbonyldiimidazole as cross-linker in a 1:3 ratio (nanosponge/cross-linker). However, for smaller molecules as phloridzin and chlorogenic acid, the nanosponge which showed the best results was the one with HMDI in a 1:8 ratio (87.2 and 77.5 %, respectively). In vitro dissolution studies of encapsulated polyphenols showed that rutin and phloridzin are better dissolved in ethanol, while chlorogenic acid is better dissolved in water. Besides, TGA, DSC, FTIR and XRPD were used as characterization techniques. Individual polyphenols and nanosponges, equimolar physical mixtures and synthesized complexes were characterized. Taking into account the obtained results, it can be confirmed that the solid products were not physical mixtures, but inclusion complexes. Thus, using these encapsulating agents, other polyphenols from apple and its by-products could be encapsulated in order to enhance their bioavailability.
Phase-controlled supramolecular photochirogenesis in cyclodextrin nanosponges
Chemical Communications, 2013
Pyromellitate-bridged cyclodextrin nanosponges (CDNSs) evolved from sol into gel state upon gradu... more Pyromellitate-bridged cyclodextrin nanosponges (CDNSs) evolved from sol into gel state upon gradual increase of the concentration from 0.2 to 2000 mg mL(-1) in water. The enantiodifferentiating geometrical photoisomerizations of (Z)-cyclooctene and (Z,Z)-1,3-cyclooctadiene sensitized by CDNS at various concentrations were critically affected by the phase transition of CDNS to afford the corresponding (E)- and (E,Z)-isomers in the highest enantiomeric excesses in the gel state.
Beilstein Journal of Organic Chemistry, 2012
Enantiodifferentiating geometrical photoisomerizations of (Z)-cyclooctene and (Z,Z)-1,3-cycloocta... more Enantiodifferentiating geometrical photoisomerizations of (Z)-cyclooctene and (Z,Z)-1,3-cyclooctadiene were performed by using the pyromellitate-linked cyclodextrin network polymer, termed "cyclodextrin nanosponge (CDNS)", as a supramolecular sensitizing host. The photochirogenic behavior of the nanosponges incorporating β-or γ-cyclodextrin was significantly different from that reported for the conventional sensitizer-appended monomeric cyclodextrins, affording chiral (E)-cyclooctene and (E,Z)cyclooctadiene in enantiomeric excesses critically dependent on the solution pH and solvent composition employed, revealing the active roles of chiral void spaces of CDNS in the photochirogenic reaction.
Synthesis and characterization of a hyper-branched water-soluble β-cyclodextrin polymer
Beilstein journal of organic chemistry, 2014
A new hyper-branched water-soluble polymer was synthesized by reacting β-cyclodextrin with pyrome... more A new hyper-branched water-soluble polymer was synthesized by reacting β-cyclodextrin with pyromellitic dianhydride beyond the critical conditions that allow the phenomenon of gelation to occur. The molar ratio between the monomers is a crucial parameter that rules the gelation process. Nevertheless, the concentration of monomers in the solvent phase plays a key role as well. Hyper-branched β-cyclodextrin-based polymers were obtained performing the syntheses with excess of solvent and cross-linking agent, and the conditions for critical dilution were determined experimentally. A hyper-branched polymer with very high water solubility was obtained and fully characterized both as for its chemical structure and for its capability to encapsulate substances. Fluorescein was used as probe molecule to test the complexation properties of the new material.
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Papers by Fabrizio Caldera