Francesco Trotta

Cyclodextrin-based nanosponges encapsulating camptothecin: Physicochemical characterization, stability and cytotoxicity

Camptothecin (CAM), a plant alkaloid and a potent antitumor agent, has a limited therapeutic utility because of its poor aqueous solubility, lactone ring instability and serious side effects. Cyclodextrin-based nanosponges (NS) are a novel class of cross-linked derivatives of cyclodextrins. They have been used to increase the solubility of poorly soluble actives, to protect the labile groups and control the release. This study aimed at formulating complexes of CAM with three types of beta-cyclodextrin NS obtained with different cross-linking ratio (viz. 1:2, 1:4 and 1:8 on molar basis with the cross-linker) to protect the lactone ring from hydrolysis and to prolong the release kinetics of CAM. Crystalline (F(1:2), F(1:4) and F(1:8)) and paracrystalline NS formulations were prepared. XRPD, DSC and FTIR studies confirmed the interactions of CAM with NS. XRPD showed that the crystallinity of CAM decreased after loading. CAM was loaded as much as 21%, 37% and 13% w/w in F(1:2), F(1:4) and F(1:8), respectively while the paracrystalline NS formulations gave a loading of about 10% w/w or lower. The particle sizes of the loaded NS formulations were between 450 and 600nm with low polydispersity indices. The zeta potentials were sufficiently high (-20 to -25mV) to obtain a stable colloidal nanosuspension. The in vitro studies indicated a slow and prolonged CAM release over a period of 24h. The NS formulations protected the lactone ring of CAM after their incubation in physiological conditions at 37 degrees C for 24h with a 80% w/w of intact lactone ring when compared to only around 20% w/w of plain CAM. The cytotoxicity studies on HT-29 cells showed that the CAM formulations were more cytotoxic than plain CAM after 24h of incubation.

Cyclodextrin-based nanosponges as drug carriers

Summary Cyclodextrin-based nanosponges, which are proposed as a new nanosized delivery system, are innovative cross-linked cyclodextrin polymers nanostructured within a three-dimensional network. This type of cyclodextrin polymer can form porous insoluble nanoparticles with a crystalline or amorphous structure and spherical shape or swelling properties. The polarity and dimension of the polymer mesh can be easily tuned by varying the type of cross-linker and degree of cross-linking. Nanosponge functionalisation for site-specific targeting can be achieved by conjugating various ligands on their surface. They are a safe and biodegradable material with negligible toxicity on cell cultures and are well-tolerated after injection in mice. Cyclodextrin-based nanosponges can form complexes with different types of lipophilic or hydrophilic molecules. The release of the entrapped molecules can be varied by modifying the structure to achieve prolonged release kinetics or a faster release. The nanosponges could be used to improve the aqueous solubility of poorly water-soluble molecules, protect degradable substances, obtain sustained delivery systems or design innovative drug carriers for nanomedicine.

Thermal degradation of cyclodextrins

Owing to environmental issues, there is now a very important request for halogen-free fire retardant polymer materials.

Molecular imprinted polymeric membrane for naringin recognition

Membranes of poly(acrylonitrile-co-acrylic acid) (PAAN) made by phase inversion technique in the presence of naringin showed molecular recognition behaviour towards the template molecule. The interactions of the carboxylic groups of the polymer chain played an important role in the discrimination process. Simple prolonged washing with ethanolic acetic acid solution regenerated the membrane without any loss of the binding capacity. No recognition properties were detected for membranes made without the imprinted molecule.

SULFONATION OF POLYETHERETHERKETONE BY CHLOROSULFURIC ACID

Sulfonated poly(oxa-p-phenylene-3,3-phthalido-p-phenylene-oxa-p-phenylene-oxy-phenylene) (PEEK-WC) with various degrees of substitution was obtained by reaction of polyetheretherketone with neat chlorosulfuric acid. Highly sulfonated PEEK-WC was freely soluble in cold water. By working under suitable reaction conditions, no degradation of the polymeric chain was detected. The modified PEEK-WC was able to form asymmetric membranes. The expected chlorosulfonated derivatives were never achieved.

Cyclodextrins as Food Additives and in Food Processing

This review deals with the applications of cyclodextrins (CDs) to food manufacture, focusing on the technical advantages of their use in food processing and as food additives. Their beneficial effects essentially derive from the ability to form stable inclusion complexes with sensitive lipophilic nutrients and constituents of flavor and taste. Toxicological data are examined and an assessment of CDs from the standpoint of safety for human consumption is made. Regulations are covered, showing a general trend towards a wider acceptance of CDs as food additives. The growing health consciousness of consumers and expanding market for functional foods and nutraceutical products are opening up to CDs a promising future in food industry.

Nanosponge formulations as oxygen delivery systems

Three types of cyclodextrin nanosponges were synthetized cross-linking α, β or γ cyclodextrin with carbonyldiimidazole as cross-linker. Nanosponges are solid nanoparticles previously used as drug carriers. In this studies cyclodextrin nanosponges were developed as oxygen delivery system. For this purpose the three types of nanosponges suspended in water were saturated with oxygen and in vitro characterized. The nanosponge safety was tested on Vero cells. Their ability to release oxygen in the presence and in the absence of ultrasound (US) was determined over time. Oxygen permeation through a silicone membrane was obtained using a β-cyclodextrin nanosponge/hydrogel combination system. Nanosponge formulations might be potential gas delivery systems showing the ability to store and to release oxygen slowly over time.

Characterization and Applications of New Hyper-Cross-Linked Cyclodextrins

Nanosponges are recently developed hyper-cross-linked cyclodextrin polymers nanostructured to form 3-dimensional networks; they are obtained by reacting cyclodextrin with a cross-linker such as carbonyldiimidazole. Nanosponges can be synthesized in neutral or acidic forms, depending in turn on the agent used as cross-linker. They are solid nanoparticles and can be prepared in crystalline form with spherical shape using an ultrasound-assisted preparation method. The average diameter of a nanosponge is below 1 μm but fractions below 500 nm can be selected. Nanosponges can encapsulate various types of molecules by forming inclusion and non-inclusion complexes. In this study we used dexamethasone as model molecule; up to 35% could be incorporated. Nanosponges could be used to increase aqueous solubility of poorly water-soluble drugs, to remove pollutants from contaminated water, or as nanocarriers for biomedical applications.

Enhanced oral paclitaxel bioavailability after administration of paclitaxel-loaded nanosponges

The aim of this study was to evaluate the pharmacokinetics of paclitaxel-loaded nanosponges (PLN) in rats. The study also evaluates the intrinsic effect of the dosage form on the improvement of paclitaxel oral bioavailability. Paclitaxel-loaded nanosponges were prepared and characterized in terms of size distribution, drug solubilization, and the kinetics of paclitaxel sedimentation. Taxol® and paclitaxel-loaded nanosponges were administered orally to rats. The plasma concentration of paclitaxel was determined using liquid chromatography. The average size of PLN was 350 ± 25 nm. The drug payload of paclitaxel was 500 ± 0.27 mg/g of lyophilized powder. The encapsulation efficiency was 99.1 ± 1.0%, and 1.7 ± 0.2% of paclitaxel was crystallized after 48 h. The relative oral bioavailability of paclitaxel-loaded nanosponges was 256. After oral administration of paclitaxel-loaded PLN, the area under the plasma concentration time curve was significantly increased (∼ 3-fold) in comparison to the control group (p < 0.05). The results indicated that PLN provided a promising new formulation to enhance the oral bioavailability of paclitaxel while avoiding the use of cremophore El: Ethanol in Taxol®.

Oxidative 4-dechlorination of 2,4,6-trichlorophenol catalyzed by horseradish peroxidase.

Abstract The well-known and easily available horseradish peroxidase (HRP) catalyzes the H2O2-dependent oxidative 4-dechlorination of the pollutant 2,4,6-trichlorophenol, which is recalcitrant to many organisms except those producing ligninases. UV-visible spectroscopy and gas chromatography-mass spectrometry identified the oxidized reaction product as 2,6-dichloro-1,4-benzoquinone. NMR and IR spectroscopic data further supported the above characterization. Experimental evidence for the elimination of HCl from the substrate was acquired by detecting the decrease in pH of the reaction mixture, and by observing the presence of the β-chlorocyclopentadienone cation fragment in the mass spectrum of 2,6-dichloro-1,4-benzoquinone. Consequently, nucleophilic attack by water on the 2,4,6-trichlorocyclohexadienone cation was proposed to give the final product. Our results indicate an oxidative dechlorination pathway catalyzed by HRP for 2,4,6-trichlorophenol, similar to that by extracellular lignin peroxidases. The relative catalytic efficiency of HRP seems higher than that of lignin peroxidases. The HRP-H2O2 catalytic system could be utilized in the degradation of polychlorinated phenols for industrial and biotechnological purposes.