Teresa Ferrarelli

Trans-ferulic acid-based solid lipid nanoparticles and their antioxidant effect in rat brain microsomes

In this study, stearic acid- and stearyl ferulate-based solid lipid nanoparticles containing trans-ferulic acid (SLN-FA and SLN-SF-FA, respectively), were prepared and characterized for loading efficiency, size and shape. In addition, by using rat brain microsomes, we evaluated in vitro the antioxidant activity of these formulations against three well known initiators of lipid peroxidation, such as AAPH, NADPH/ADP-Fe(3+) and SIN-1 which in turn generate the peroxyl and perferryl radicals as well as peroxynitrite, respectively. Commercially available FA and its ethyl ester (FAEE) were used as comparators. Both SLN-FA and SLN-SF-FA dose-dependently reduced lipid peroxidation induced by the three oxidants. Interestingly, SLN-SF-FA displayed greater efficacy (EC50) and potency (maximal activity) against AAPH- and NADPH/ADP-Fe(3+)-induced lipid peroxidation. Our results support the idea that this new formulations could facilitate the uptake of FA by the cells because of their lipophilic structure, thus increasing FA bioavailability. Furthermore, stearyl ferulate-based nanoparticles could prevent the degradation of FA entrapped on their structure, making FA almost entirely available to explicate its antioxidant power once released.

New sucrose cocoate based vesicles: Preparation characterization and skin permeation studies

A commercial sucrose cocoate surfactant was used to obtain a new vesicular system for transdermal drug delivery. The preparation, the dimensional and morphological characterizations and the skin permeation profile of these new niosomes were evaluated. Moreover we studied the possible employment of mixture of sucrose cocoate and cholesterol at different weigh ratios for the vesicles preparation and we analyzed the influence of cholesterol on niosomes properties. Diclofenac and Sulfadiazine were used as model drugs. Results suggest that sucrose cocoate was able to form vesicles in the presence or not of cholesterol and the addition of cholesterol leads to a variation of size: larger vesicles were obtained in the absence of cholesterol both in empty and drug-loaded niosomes. All vesicles were spherical and regular in shape. In vitro skin permeation profiles were significantly higher than the free drug solution, indicating the favourable relations between skin and niosomes. The faster release of the drug was found for niosomes with no cholesterol or with a reduced amount of this membrane additive, in particular the optimal formulation was that in which the cholesterol content was about 27 wt% of total lipid amount: probably this value is a good compromise between the membrane stability and its deformation capacity, allowing a higher drug permeation across the skin.

Isoniazid-gelatin conjugate microparticles containing rifampicin for the treatment of tuberculosis

In this work, a new polymeric microparticle system based on gelatin covalently bound to isoniazid (ISN) and containing rifampicin (RFP) was prepared by spray‐drying technique. Microparticle aptitude to nebulisation and their capability of interacting with A549, alveolar basal epithelial cells, were evaluated in vitro.

Respirable rifampicin-based microspheres containing isoniazid for tuberculosis treatment

The purpose of this investigation was to develop small microspheres for delivering antimycobacterial drugs to infected host macrophages. Rifampicin-based microparticles were prepared. The drug was covalently linked to acrylic moieties to obtain a polymerizable derivative for the preparation of materials useful as drug delivery systems that then were loaded with isoniazid acting in synergy with rifampicin. Their antitubercular activity was determined in vitro. Fourier transform infrared spectroscopy confirmed hydrogel structure. Morphological analysis showed microparticles with spherical shape and homogeneous surface. In vitro release studies were performed in media simulating physiologic pH (7.4) and endosomal of alveolar macrophages pH (5.2). A similar amount of isoniazid was delivered within the first 6 h at both pHs, while a smaller amount of the drug was delivered at pH 7.4 in the last phase of the study. In vitro antitubercular activity showed a behavior comparable to that of rifampicin and isoniazid free. Bioactive swelling matrices, showing a high swelling degree into a medium miming intra alveolar environment, were obtained. They could be applied for their antitubercular activity.

Preparation, characterization and in vitro activities evaluation of solid lipid nanoparticles based on PEG-40 stearate for antifungal drugs vaginal delivery

Abstract The present article reports the preparation, characterization and performance evaluation of solid lipid nanoparticles (SLNs) based on polyoxyethylene-40 stearate (PEG-40 stearate) for the administration of antifungal agents such as ketoconazole and clotrimazole. These nanoparticles could be useful in the treatment of vaginal infections sustained by Candida albicans. In particular, PEG-40 stearate was made to react with acryloyl chloride in order to introduce an easily polymerizable moiety for the creation of a second shell and to ensure a slow drug release. In addition, the differences on the release profiles between PEG-40 stearate-based nanoparticles, PEG-40 stearate acrylate based and polymerized ones, were analyzed under conditions, simulating the typical environment of Candida albicans infection. Then, the antifungal activity of nanoparticles was also evaluated in terms of minimal inhibitory concentration. Moreover, the nanoparticles were submitted to in vitro studies for evaluating the drug permeability at the site of action. Results indicated that the obtained particles are potentially useful for the treatment of vaginal infections sustained by Candida albicans.

Synthesis, Characterization, and Anti-Inflammatory Activity of Diclofenac-Bound Cotton Fibers

In the present work, we report on the synthesis of cellulose cotton fibers covalently linked to diclofenac moieties and the evaluation of the anti-inflammatory activity of this new biomaterial. In spite of recent progress in experimental and clinical medicine, the problem of chronic wounds treatment is still debated. In fact, conventional methods are based on the use of ointment-soaked bandages, but several physical and biological factors contribute to making the efficacy of this method quite low. For this reason, we developed the idea to using modified cotton gauzes to prevent inflammation during wound healing. In this light, diclofenac, a nonsteroidal anti-inflammatory drug, was covalently linked to the cellulose backbone of hydrophilic cotton fibers by a heterogeneous synthesis to produce a functionalized biopolymer with a satisfactory degree of substitution and anti-inflammatory activity. Diclofenac was directly linked to fiber microfibril hydroxylic groups using THF with thionyl chloride. The obtained biopolymer was characterized by infrared spectroscopy (FT-IR) to confirm ester linkages. Finally, the anti-inflammatory activity was evaluated in a well-established in vivo model. The results suggested that these biomaterials possess an excellent anti-inflammatory activity in vivo, so they can be efficiently employed in biomedical fields for chronic wound management to ensure a valid protection against inflammation.

Hemp fiber (Cannabis sativa L.) derivatives with antibacterial and chelating properties

AbstractThe aim of this study was to synthesize a new antibacterial and chelating biopolymer and to evaluate its germicidal activity and its ability in metal ions removal from aqueous solutions. The material was prepared via esterification of hemp with 2-benzyl-4-chlorophenol, a germicide agent, that was covalently coupled to cellulose backbone of hydrophilic fibers by a heterogeneous synthesis, to produce a functionalized biopolymer with a satisfactory degree of substitution. The obtained biopolymer was characterized by infrared spectroscopy and differential scanning calorimetry. Its antibacterial activity in inhibiting Staphylococcus aureus and Pseudomonas aeruginosa growth in Petri dishes, was evaluated. The results suggested that this biomaterial possesses an excellent in vitro antibacterial activity and so it can be efficiently employed in biomedical fields to ensure a protection against contaminations. On the other hand, the functionalized biopolymer interacts with metal ions thanks to its chelating functional groups. The absorption capacity for a selected metal ion such as Cd(II), was investigated in aqueous solution at pH 0.65, 4.1 and 7.0 by optical emission spectroscopy. This study showed that the new system is very effective in chelating cadmium ions showing the maximum efficiency at pH 4.1. This feature makes the synthesized biomaterial a potential candidate for metal ions removal.Graphical AbstractHemp fiber (Cannabis sativa L.) derivatives with antibacterial and chelating properties. Roberta Cassano, Sonia Trombino, Teresa Ferrarelli, Fiore Pasquale Nicoletta, Maria Vittoria Mauro, Cristina Giraldi, Nevio Picci

Synthesis, characterization and in-vitro antitubercular activity of isoniazid-gelatin conjugate

Objectives  A novel and simple method to synthesize antitubercular‐protein conjugate by solid phase synthesis was developed employing a carboxypolystyrene resin. The aim was to covalently bind a drug with antitubercular activity, isoniazid, to a biomacromolecule, gelatin, widely used in the pharmaceutical, cosmetic and food industry.

Preparation, Characterization and Efficacy Evaluation of Synthetic Biocompatible Polymers Linking Natural Antioxidants

The purpose of this work was the synthesis, characterization and efficacy evaluation of new biocompatible antioxidant polymers linking trans-ferulic acid or α-lipoic acid. In particular, ferulic or lipoic acid were introduced in the preformed polymeric backbone. The new antioxidant biopolymers were characterized by Fourier transform infrared spectroscopy and gel permeation chromatography. The degree of functionalization (moles of antioxidant per gram of polymer) was determined by the Gaur-Gupta method for free amino group determination and by the Folin method for the phenolic groups. Their ability to inhibit lipid peroxidation were estimated in rat liver microsomal membranes induced in vitro by tert-BOOH (tert-butyl hydroperoxide), as a source of free radicals. The DPPH (1,1-diphenyl-2-picrylhydrazyl) radical-scavenging effect was also evaluated. The obtained systems, with different solubility, showed strong antioxidant and antiradical activities, suggesting potential use as packaging materials for foods, cosmetics, pharmaceuticals and personal care products. Moreover, the cytotoxicity of the synthesized polymers was also evaluated on Caco-2 cell cultures in order to verify their biocompatibility when exposed to an absorptive epithelial cell line.

Dextran-pegylated microparticles for enhanced cellular uptake of hydrophobic drugs

Polyethylene glycol monosubstituted with a polymerizable acrylic moiety was linked to 6-carboxy free position on dextran side chains and then subjected to radical polymerization with a comonomer in order to obtain microspheres for the oral controlled release of ketoconazole, a hydrophobic model drug. Microparticles were submitted to studies on their ability to absorb and retain water. Cell uptake studies, in the presence and absence of mucus, across two different monolayers, respectively, HT29-MTX-E12 and Caco-2, were done. Cytotoxicity studies were carried out to calculate the IC₅₀ value. The ability of microspheres to open monolayers tight junctions was tested by measuring their TEER values. Images of cell uptake were visualized by CLSM. In HT29-MTX-E12 cells, more mucoadhesion and drug internalization is seen thanks to the presence of PEG and dextran chains.