Fabrizio Caldera

Novel cyclodextrin nanosponges for delivery of calcium in hyperphosphatemia.

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 accelerated stability study no significant changes occurred in physical appearance, size and nature of drug in formulation for 3 months. The results of FTIR and DSC confirmed that calcium carbonate was encapsulated in nanosponges structure.

The application of nanosponges to cancer drug delivery

Introduction: 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. Area covered: 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. Expert opinion: Cyclodextrin-based nanosponges can be considered a challenging technology for the development of innovative formulations, suitable for various administration routes for anti-cancer drugs.

Phase-controlled supramolecular photochirogenesis in cyclodextrin nanosponges

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.

Acute and Repeated Dose Toxicity Studies of Different β-Cyclodextrin-Based Nanosponge Formulations

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.

Molecularly imprinted cyclodextrin nanosponges for the controlled delivery of L-DOPA: perspectives for the treatment of Parkinson's disease.

ABSTRACT Background: L-DOPA is an amino acid precursor to the neurotransmitter dopamine that is extensively used as a prodrug for the treatment of Parkinson’s disease. However, L-DOPA is an unstable compound: when exposed to light or added to aqueous solutions, it may degrade, compromising its therapeutic properties. Methods: In this work, a new type of drug-loaded cyclodextrin-based nanosponge, obtained using molecular imprinting, is described for the prolonged and controlled release of L-DOPA. The molecularly imprinted nanosponges (MIP-NSs) were synthesized by cross-linking β-cyclodextrin with 1,1ʹ-carbonyldiimidazole in DMF in the presence of L-DOPA as a template molecule. TGA, DSC and FTIR analyses were performed to characterize the interactions between L-DOPA and the two nanosponge structures. Quantitative NMR spectroscopy was used to determine the amount and the affinity of L-DOPA entrapped in the nanosponges. The in vitro L-DOPA release kinetics from the NSs were quantitatively determined by HPLC analysis. Results: The MIP-NSs show a slower and more prolonged release profile than the non-imprinted nanosponges. No degradation of the L-DOPA hosted in the MIP-NSs was observed after long-term storage at room temperature. Conclusions: The MIP-NSs are a promising alternative for the storage and controlled delivery of L-DOPA.

Molecularly Imprinted Membranes

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.

Cyclodextrin nanosponge-sensitized enantiodifferentiating photoisomerization of cyclooctene and 1,3-cyclooctadiene

Summary 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.

Evolution of Cyclodextrin Nanosponges

Cyclodextrin-based nanosponges (CD-NSs) are insoluble, highly cross-linked 3D network polymers used in several scientific and technological fields, the main area of investigation concerns the pharmaceutical applications, in which CD-NSs have been mostly employed as drug delivery systems. CD-NSs can be generally grouped into four consecutive generations, taking into account their chemical composition and properties. The 1st generation of NSs are plain nanosponges, subdivided into four main types: urethane, carbonate, ester and ether NSs, depending on the chemical nature of the functional group connecting the CD to the cross-linker. The 2nd generation of NSs are modified nanosponges characterized by specific properties, such as fluorescence and electric charge. The 3rd generation of NSs is represented by stimuli-responsive CD polymers, which are able to modulate their behavior according to external variations in the environment, such as pH and temperature gradients, oxidative/reducing conditions, and finally the 4th generation of NSs, a new family of molecularly imprinted CD polymers (MIPs), exhibiting a high selectivity towards specific molecules. The following review focuses on the evolution of cyclodextrin nanosponges, listing some examples of each generation.

Tuning structural parameters for the optimization of drug delivery performance of cyclodextrin-based nanosponges

ABSTRACT Introduction: 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. Areas covered: 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. Expert opinion: 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.

Preparation of functionalized cotton fabrics by means of melatonin loaded β-cyclodextrin nanosponges

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.