Papers by Giuseppe Cirillo
Development of novel radiochemotherapy approaches targeting prostate tumor progenitor cells using nanohybrids
International journal of cancer. Journal international du cancer, Jan 9, 2015
Many tumors including prostate cancer are maintained by cancer stem cells (CSCs), which might cau... more Many tumors including prostate cancer are maintained by cancer stem cells (CSCs), which might cause tumor relapse if not eradicated during the course of treatment. Specific targeting or radiosensitization of CSCs bear promise to improve tumor curability by synergistic effects in combination with radiotherapy. Carbon nanotubes (CNTs) can be used as promising drug delivery systems for anticancer drugs such as the flavonoid catechin. Catechin is an extensively studied active ingredient of the different plants, including green tea, and it is widely recognized as co-adjuvant in cancer therapy. Here we describe the synthesis of biocompatible, catechin-loaded and gelatin-conjugated CNTs (Gel_CT_CNTs) with anticancer properties and demonstrate their potential for the eradication of prostate CSCs in combination with X-ray irradiation. Gel_CT_CNTs showed a significant enhancement of in vitro anticancer activity as compared to catechin alone. Moreover, treatment of prostate cancer cells with G...
Talanta, 2011
This paper presents a new LC method with evaporative light scattering detection (ELSD), for the s... more This paper presents a new LC method with evaporative light scattering detection (ELSD), for the separation and determination of the biogenic amines (histamine, spermidine, spermine, tyramine, putrescine and β-phenylethylamine) which are commonly present in cheese, as their presence and relative amounts give useful information about freshness, level of maturing, quality of storage and cheese authentication. The LC–ELSD method is validated
Tunable thermo-responsive hydrogels: synthesis, structural analysis and drug release studies
Materials science & engineering. C, Materials for biological applications, 2015
Thermo-responsive hydrogel films, synthesized by UV-initiated radical polymerization, are propose... more Thermo-responsive hydrogel films, synthesized by UV-initiated radical polymerization, are proposed as delivery devices for non-steroidal anti-inflammatory drugs (Diclofenac sodium and Naproxen). N-isopropylacrylamide and N,N'-ethylenebisacrylamide were chosen as thermo-sensitive monomer and crosslinker, respectively. Infrared spectroscopy was used to assess the incorporation of monomers into the network, and the network density of hydrogel films was found to strictly depend on both feed composition and film thickness. Calorimetric analyses showed negative thermo-responsive behaviour with shrinking/swelling transition values in the range 32.8-36.1°C. Equilibrium swelling studies around the LCST allowed the correlation between the structural changes and the temperature variations. The mesh size, indeed, rapidly changed from a collapsed to a swollen state, with beneficial effects in applications such as size-selective permeation or controlled drug delivery, while the crosslinking d...
Synthesis, characterization and antimicrobial activity of conjugates based on fluoroquinolon-type antibiotics and gelatin
Journal of materials science. Materials in medicine, 2014
Different fluoroquinolon-type antibiotics were conjugated to gelatin with the aim to synthesize b... more Different fluoroquinolon-type antibiotics were conjugated to gelatin with the aim to synthesize biomacromolecules with antimicrobial properties. The covalent linkage of the antibiotic was performed by a radical process involving the residues in the side chains of gelatin able to undergo oxidative modifications. The conjugation of antibiotic moieties onto the protein structure was confirmed by FT-IR, UV-Vis, fluorescence, and calorimetric analyses. Biocompatibility tests were performed on human bone marrow mesenchymal stromal cells and the antibacterial properties of bioactive polymers were investigated by appropriate tests against Klebsiella pneumoniae and Escherichia coli. With regard to the tests conducted in the presence of E. coli, a minimum inhibitory concentration (MIC) ranging from 0.05 to 0.40 μg mL(-1) was recorded, while in the presence of K. pneumoniae this concentration varies from 0.10 to 1.60 μg mL(-1). In all the conjugates, the drug moieties retain their biological a...
Polyphenol conjugates and human health: a perspective review
Critical Reviews in Food Science and Nutrition, 2014
Abstract In recent years, antioxidants have gained great importance because of their potential us... more Abstract In recent years, antioxidants have gained great importance because of their potential use in food, pharmaceutical, and cosmetic industries. This interest is rooted in the cumulative evidence connecting active oxygen and free radicals with numerous human degenerative disorders such as cardiovascular diseases, cancer, aging, and atherosclerosis. Polyphenols are the major class of antioxidant able to reduce the oxidative damages of lipids, proteins, enzymes, carbohydrates, and DNA in living cells and tissues. Among the realm of polyphenol compounds, polyphenol conjugates have been proposed as innovative materials which, by combining the advantageous properties of both the components, can increase the efficiency of antioxidants and their range of application in nutritional and biomedical fields. This work is an overview of the different class of polyphenol conjugates, which will be analyzed in terms of nutritional and biological properties, showing how these bio-conjugates will positively affect the human health.
Food Chemistry, 2015
Eight biogenic amines (spermine, spermidine, putrescine, histamine, tyramine, phenylethylamine, c... more Eight biogenic amines (spermine, spermidine, putrescine, histamine, tyramine, phenylethylamine, cadaverine and serotonin) were determined by LC-UV after derivatization with dansyl-chloride in both ground coffee and coffee beverages obtained by different methods. In ground coffee, the most relevant amine was PUT, followed by SPD, HIS, TYR, CAD, SPM, PHE, and SER, with the total BAs content decreasing as the roasting degree increased. In coffee brews, the order was PUT, SPM, TYR, CAD, SPD, PHE, HIS, and SER, but at a very low level in comparison with the amount of BAs determined in roasted ground coffee. Beverages prepared by espresso, capsule, and pod machines had the lowest BAs contents, as a result of the thermal and physical stress imposed on ground coffee by these methods, while mocha contained the highest BAs amounts owing to lower pressure and longer brewing time.
RSC Adv., 2014
The most exciting promise of cell micro-bioreactors is their expected ability to reproduce specif... more The most exciting promise of cell micro-bioreactors is their expected ability to reproduce specific aspects of physiological environments in vitro, singularly or in combination, and to perform advanced biological studies to unravel novel interaction mechanisms; but this challenge is formidable. Moreover, the use of microfluidics is limited by the difficulty to adapt standard tissue culture protocols to miniaturised biochips and by the need of bulky external equipment such as liquid pumping systems. Here, we introduce an original microfluidic gradient generator for culturing cells in closed microchambers, based on: (1) automatic cell valving, (2) hydrostatic-pressure pumping, and (3) on-chip liquid reservoirs. The biochip is designed to be fully compatible with standard biological procedures and to operate with no external control units or cumbersome ancillary components. Remarkably, the use of integrated liquid reservoirs prevents air bubble formation and associated channel clogging. We detail the rationale behind the fluidic design, simulate and measure the chip fluid-dynamics by finite element simulations and microflow velocimetry, respectively. We finally exploit our chip to study the kinetics of an anti-cancer molecule, the catechin-dextran conjugate, on HeLa cells, demonstrating a very fast action. We argue that the presented fluidic concept and architecture are not limited to the present realization, but can be easily applied to other chip geometries and adapted to a number of biological studies.
Food Chemistry, 2008
In this study, a novel sample clean-up technique based on the molecularly imprinted solid-phase e... more In this study, a novel sample clean-up technique based on the molecularly imprinted solid-phase extraction procedure is described for the determination of trifluoperazine (TFP) in biological fluids. The water-compatible molecularly imprinted polymers (MIPs) were prepared by using methacrylic acid as functional monomer, ethylene glycol dimethacrylate as cross-linker, chloroform as porogen and TFP as the template molecule. The novel imprinted polymer was used as a solid-phase extraction sorbent for the extraction of TFP from human serum and urine samples. Various parameters affecting the extraction efficiency of the polymer were evaluated. The selectivity of MIPs was evaluated by checking several substances with molecular structures similar to the template. The limits of detection and quantification for TFP in urine samples were 0.06 and 0.2 mg/L, respectively. These limits for TFP in serum samples were 0.15 and 0.4 mg/L, respectively. The recovery values for serum and urine samples were higher than 92 and 93%, respectively.
Molecularly imprinted polymers as drug delivery systems for the sustained release of glycyrrhizic acid
Journal of Pharmacy and Pharmacology, 2010
The aim was to synthesize molecularly imprinted polymers (MIPs) with high recognition properties ... more The aim was to synthesize molecularly imprinted polymers (MIPs) with high recognition properties towards glycyrrhizic acid and to evaluate the performance of these materials to act as base excipients in glycyrrhizic acid sustained release in gastrointestinal simulating fluids. MIPs were synthesized using methacrylic acid (MAA) as acidic, 2-(dimethylamino)ethyl methacrylate (DMAEMA) as basic, and 2-hydroxyethylmethacrylate (HEMA) as neutral functional monomers, while ethylene glycol dimethacrylate (EGDMA) was chosen as a crosslinking agent. The imprinting effect was evaluated by binding experiments using glycyrrhizic acid and glycyrrhetic acid (analogue molecule) solutions and in-vitro release studies were performed in gastrointestinal simulating fluids. Good recognition and selectivity properties were found in all the synthesized materials in both ethanol and ethanol-water mixture. The release from non-imprinted polymers was indeed higher at acidic pH, while a slower release was observed in MIPs' case, because of the presence of imprinted cavities in the polymeric structure. The stronger capacity of MAA to interact by hydrogen bonds with the template makes MAA-containing MIPs the most effective materials in both rebinding and release experiments. The release tests confirm the applicability of imprinted polymer for glycyrrhizic acid sustained release in gastrointestinal simulating fluids.
Food Chemistry, 2011
A new Molecularly Imprinted Solid Phase Extraction (MISPE) protocol was developed for the selecti... more A new Molecularly Imprinted Solid Phase Extraction (MISPE) protocol was developed for the selective extraction and purification of glycyrrhizic acid (GL) from liquorice roots. Non-covalent MIP were synthesized using methacrylic acid (MAA), 2-(dimethylamino)ethyl methacrilate (DMAEM) or 2-hydroxyethylmetacrylate (HEMA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent.After the evaluation of the selectivity of the GL imprinted polymers, the
Spherical gelatin/CNTs hybrid microgels as electro-responsive drug delivery systems
International Journal of Pharmaceutics, 2013
Novel spherical hybrid hydrogels composed of gelatin and multi-walled carbon nanotubes were synth... more Novel spherical hybrid hydrogels composed of gelatin and multi-walled carbon nanotubes were synthesized by emulsion polymerization in the presence of sodium methacrylate and N,N'-ethylenebisacrylamide, and proposed as drug delivery microspheres for the electro-responsive release of Diclofenac sodium salt. Different amounts of nanotubes (up to 35% by weight) were covalently inserted into the polymeric network in order to determine the percentage conferring the highest electric sensitivity to the composite microspheres. Characterization of hydrogels was performed by electrical, morphological and calorimetric analyses, Raman measurements, biocompatibility assays and evaluation of the swelling behaviors in water (pH 1.0 and pH 7.4) with and without the application of an external electric field. Finally, the release profiles were determined and the diffusion behavior was evaluated by semi-empirical equations.
Incorporation of carbon nanotubes into a gelatin-catechin conjugate: Innovative approach for the preparation of anticancer materials
International Journal of Pharmaceutics, 2013
A new hybrid material made of gelatin, catechin and carbon nanotubes was prepared by the non-cova... more A new hybrid material made of gelatin, catechin and carbon nanotubes was prepared by the non-covalent incorporation of carbon nanotubes (CNTs) into a gelatin-catechin covalent conjugate. The composite materials was tested by means of determination of the dispersion stability in water and the functionalization degree was assessed by the Folin-Ciocalteu method, finding a 0.9 mg of CT/g of protein conjugate. Subsequently, the complete retention of the antioxidant properties of the flavonoid after incorporation into the composite was proved by DPPH and ABTS assays and IC50 values of 5.74 mg mL(-1) and 0.39 mg mL(-1) were recorded. The presence of CNT into the materials did not interfere with the scavenging activities of the catechin. Finally, the anticancer activity on HeLa cancer cells was evaluated and a considerable increase in the therapeutic activity of the flavonoid was recorded moving from the free to the conjugated form in the presence of CNT, while in absence of CNT a reduction of the efficiency was observed.
Journal of Functional Biomaterials, 2012
The synthesis of a novel functional biomaterial for wound healing treatment was carried out by ad... more The synthesis of a novel functional biomaterial for wound healing treatment was carried out by adopting a free-radical grafting procedure in aqueous media. With this aim, ciprofloxacin (CFX) was covalently incorporated into collagen (T1C) chains employing an ascorbic acid/hydrogen peroxide redox pair as biocompatible initiator system. The covalent insertion of CFX in the polymeric chains was confirmed by FT-IR and UV analyses, while an antibacterial assay demonstrated the activity of the synthesized conjugate against Staphylococcus aureus and Escherichia coli, microorganisms that commonly infect wounds. A catechin blended conjugate was also tested in order to evaluate the ability to influence fibroblast cell growth. The observed antibacterial activity and stimulation of fibroblast growth support the applicability of CFX-T1C conjugate in wound treatment encouraging the healing process. OPEN ACCESS J. Funct. Biomater. 2012, 3 362
Talanta, 2011
This paper presents a new LC method with evaporative light scattering detection (ELSD), for the s... more This paper presents a new LC method with evaporative light scattering detection (ELSD), for the separation and determination of the biogenic amines (histamine, spermidine, spermine, tyramine, putrescine and -phenylethylamine) which are commonly present in cheese, as their presence and relative amounts give useful information about freshness, level of maturing, quality of storage and cheese authentication. The LC-ELSD method is validated by comparison of the results with those obtained through LC-UV determination, based on a pre-column dansyl chloride derivatisation step. The obtained data demonstrate that both methods can be interchangeably used for biogenic amines determination in cheese. The new LC-ELSD method shows good precision and permits to achieve, for standard solutions, limit of detection (LOD) values ranging from 1.4 to 3.6 mg L −1 and limit of quantitation (LOQ) values ranging from 3.6 to 9.3 mg L −1 . The whole methodology, comprehensive of the homogenization-extraction process and LC-ELSD analysis, has been applied in the analysis of a typical Calabria (Southern Italy) POD cheese, known as Caciocavallo Silano. The most aboundant amine found was histamine, followed, in decreasing order, by tyramine, spermine, putrescine, -phenylethylamine and spermidine, for a total amount of 127 mg kg −1 . This value does not represent a possible risk for consumer health, according to the toxicity levels reported in literature and regarded as acceptable.
Dextran-Catechin Conjugate: A Potential Treatment Against the Pancreatic Ductal Adenocarcinoma
Pharmaceutical Research, 2012
A polysaccharide-flavonoid conjugate was developend and proposed for the treatment of pancreatic ... more A polysaccharide-flavonoid conjugate was developend and proposed for the treatment of pancreatic ductal adenocarcinoma (PDAC). The conjugate was synthesized by free radical grafting reaction between catechin and dextran. The chemical characterization of the conjugate was obtained by UV-Vis, 1H-NMR, FT-IR and GPC analyses, while the functionalization degree was determined by the Folin-Ciocalteu assay. The biological activity of the catechin-dextran conjugate was tested on two different cell lines derived from human pancreatic cancer (MIA PaCa-2 and PL45 cells), and the toxicity towards human pancreatic nestin-expressing cells evaluated. Both the cancer cell lines are killed when exposed to the conjugate, and undergo apoptosis after the incubation with catechin-dextran which resulted more effective in killing pancreatic tumor cells compared to the catechin alone. Moreover, our experimental data indicate that the conjugate was less cytotoxic to human pancreatic nestin-expressing cells which are considered a good model of non-neoplastic pancreatic cells. The suitability of newly synthesized Dextran-Catechin conjugate in the treatment of PDAC was proved confirming the high potential application of the proposed macromolecula system in the cancer therapy.
Starch-quercetin conjugate by radical grafting: synthesis and biological characterization
Pharmaceutical Development and Technology, 2012
A novel flavonoid-polysaccharide conjugate was synthesized by free radical grafting of quercetin ... more A novel flavonoid-polysaccharide conjugate was synthesized by free radical grafting of quercetin on starch. The covalent insertion of quercetin in the polymeric chain was confirmed by FT-IR, DSC and fluorescence analyses, while an estimation of the amount of quercetin bound per g of polymer was obtained by the Folin-Ciocalteu assay. The conjugate shows improved UV stability and retains the antioxidant properties of free quercetin, such as scavenging activity towards free radicals (DPPH and peroxynitrite); inhibition of the free radical formation (peroxidation of linoleic acid) and total antioxidant activity. The conjugate also prevented drug degradation and shows potential health functionality in the treatment of Alzheimer disease, diabetes and as skin-whitening agent.
Gastro-intestinal sustained release of phytic acid by molecularly imprinted microparticles
Pharmaceutical Development and Technology, 2010
In this work, the possibility to employ molecularly imprinted polymers as base excipients for con... more In this work, the possibility to employ molecularly imprinted polymers as base excipients for controlled drug delivery devices was demonstrated. As template molecule, our attention was focused on phytic acid, a water soluble antioxidant compound. The possibility to raise a controlled/sustained release of an antioxidant agent is very useful from an application point of view; in recent years, indeed, biomedical applications of antioxidants have greatly grown because the link between human diseases and oxidative stress were proved. Polymers were synthesized using methacrylic acid as functional monomer and N,N'-Ethylenebis(acrylamide) as crosslinker. After the evaluation of the imprinting efficiency of the synthesized materials by binding experiments in which the percentage of phytic acid bounded by the molecularly imprinted polymers was found to be remarkably higher compared to the non-imprinted ones, MIP were tested as a controlled release device for the antioxidant in gastrointestinal simulating fluids.
Nutrients, 2011
In this work, the efficacy of fig syrup, a Mediterranean fig derivative, as a nutraceutical suppl... more In this work, the efficacy of fig syrup, a Mediterranean fig derivative, as a nutraceutical supplement, was demonstrated. Fig syrup is a fruit concentrate used as a common ingredient in the preparation of typical foods, and particularly in cakes. In vitro assays were performed to determine the amount of nutraceutical ingredients, such as phenolic compounds (3.92 mg equivalent of gallic acid per g) and flavonoids (0.35 mg equivalent of catechin per g), while HPLC analyses provided specific information about the composition of antioxidants in the syrup. Furthermore, total antioxidant activity, scavenging properties against DPPH and peroxyl radicals, and the anticholinesterase activity, clearly showed the efficacy of the syrup in preventing damage induced by free radicals and, thus, the applicability of this food derivative as a nutraceutical supplement.
Molecules, 2007
The aim of this work was to investigate the possibility of employing Molecularly Imprinted Polyme... more The aim of this work was to investigate the possibility of employing Molecularly Imprinted Polymers (MIPs) as a controlled release device for 5-fluorouracil (5-FU) in biological fluids, especially gastrointestinal ones, compared to Non Imprinted Polymers (NIPs). MIPs were synthesized using methacrylic acid (MAA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent. The capacity of the polymer to recognize and to bind the template selectively in both organic and aqueous media was evaluated. An in vitro release study was performed both in gastrointestinal and in plasma simulating fluids. The imprinted polymers bound much more 5-Fu than the corresponding non-imprinted ones and showed a controlled/sustained drug release, with MIPs release rate being indeed much more sustained than that obtained from NIPs. These polymers represent a potential valid system for drug delivery and this study indicates that the selective binding characteristic of molecularly imprinted polymers is promising for the preparation of novel controlled release drug dosage form.
Macromolecular Bioscience, 2005
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Papers by Giuseppe Cirillo