Cristina Bonferoni

Solid state characterisation of silver sulfadiazine loaded on montmorillonite/chitosan nanocomposite for wound healing.

Biopolymer chitosan/montmorillonite nanocomposites loaded with silver sulfadiazine for wound healing purposes were prepared via intercalation solution technique. Structure and morphology of loaded nanocomposites were studied and compared with pure components and unloaded nanocomposites. X-ray diffraction, Fourier transformed infrared spectroscopy, high resolution transmission electron microscopy coupled with energy-dispersion X-ray analysis, thermal and elemental analysis were employed for the characterisation. The results confirmed that the drug was effectively loaded in the three-dimensional nanocomposite structures, in which chitosan chains were adsorbed in monolayers into the clay mineral interlayer spaces.

Dissolution Enhancement of an Insoluble Drug by Physical Mixture with a Superdisintegrant: Optimization with a Simplex Lattice Design

The aim of the present work was to optimize a tablet formulation containing a physical mixture of a practically insoluble drug (prednisone) with a superdisintegrant (croscarmellose sodium) and two filler-binders characterized by differing water solubility (dicalcium phosphate dihydrate and anhydrous beta-lactose). Crushing strength, disintegration, and dissolution were measured for 10 formulations distributed over a factor space according to a simplex lattice design for a special cubic model. Multiple linear regression analysis was used to assess the best fit for each variable. The model predicted that increasing the amount of disintegrant to a critical amount (50%) would result in reduced disintegration time for dicalcium phosphate/beta-lactose ratios > 0.3, no changes in disintegration time for ratios < 0.3, and for all ratios an improvement in dissolution at 10 min. Crushing strength values of dicalcium phosphate increased with increasing disintegration concentration but not for beta-lactose tablets. The physical mixture of a practically insoluble drug with a superdisintegrant was confirmed as a valid approach to the improvement of dissolution, even in presence of other components. The solubility of the filler-binders influenced the minimum amount of disintegrant needed; when a soluble diluent was used, the amount of disintegrant required was reduced.

Intestinal permeability of oxytetracycline from chitosan-montmorillonite nanocomposites

A nanocomposite based on chitosan and montmorillonite was developed as carrier to improve oral bioavailability of oxytetracycline. The nanocomposite was prepared by simple solid-liquid interaction and loaded with the drug. The loaded nanocomposite was characterized by X-ray powder diffraction, thermal analysis, FTIR spectroscopy and zeta potential. Caco-2 cell cultures were used to evaluate in vitro cytotoxicity and drug permeation. Confocal laser scanning microscopy was also performed to evaluate the eventual entrapment of drug into the Caco-2 cells. Results showed that the nanocomposite was internalized into the cells and effectively enhanced drug permeation, being also biocompatible towards Caco-2 cells.

All natural cellulose acetate-Lemongrass essential oil antimicrobial nanocapsules.

Nanocapsules and nanoparticles play an essential role in the delivery of pharmaceutical agents in modern era, since they can be delivered in specific tissues and cells. Natural polymers, such as cellulose acetate, are becoming very important due to their availability, biocompatibility, absence of toxicity and biodegradability. In parallel, essential oils are having continuous growth in biomedical applications due to the inherent active compounds that they contain. A characteristic example is lemongrass oil that has exceptional antimicrobial properties. In this work, nanocapsules of cellulose acetate with lemongrass oil were developed with the solvent/anti-solvent method with resulting diameter tailored between 95 and 185nm. Various physico-chemical and surface analysis techniques were employed to investigate the formation of the nanocapsules. These all-natural nanocapsules found to well bioadhere to mucous membranes and to have very good antimicrobial properties at little concentrations against Escherichia coli and Staphylococcus aureus.

Development of sponge-like dressings for mucosal/transmucosal drug delivery into vaginal cavity

The aim of the present work was the development of vaginal sponge-like dressings based on chitosan ascorbate (CS) and on hyaluronic acid sodium salt/lysine acetate (HAS) combination. Sponge-like dressings were prepared by freeze-drying and characterized for mechanical resistance and mucoadhesion. CS dressings show higher mechanical and mucoadhesion properties in comparison with HAS dressing. The enzymatic inhibition properties of the dressings were evaluated in vitro against carboxipeptidase A in view of their employment for vaginal delivery of peptidic drugs. All the dressings were able to inhibit carboxipeptidase activity; CS dressings, independently of polymer MW, completely inhibited enzyme activity. Release and penetration enhancement properties of the dressings loaded with a high molecular weight hydrophilic molecule, fluorescein isothiocyanate dextran (FD4), were assessed. CS dressings were able to prolong FD4 release. All the dressings showed penetration enhancement properties into pig vaginal mucosa although to a different extent: greater for dressings based on CS than for that containing HAS. Moreover, CS dressings demonstrated intrinsic antimicrobial properties. The suitability of sponge-like systems for the treatment of vaginal infections was assessed by loading the CS dressing characterized by the best mechanical and antimicrobial properties with an antibiotic drug (clyndamicin-2-phosphate) and by checking drug release.

In vitro lipolysis tests on lipid nanoparticles: comparison between lipase/co-lipase and pancreatic extract

Abstract Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLC) are lipid nanocarriers aimed to the delivery of drugs characterized by a low bioavailability, such as poorly water-soluble drugs and peptides or proteins. The oral administration of these lipid nanocarriers implies the study of their lipolysis in presence of enzymes that are commonly involved in dietary lipid digestion in the gastrointestinal tract. In this study, a comparison between two methods was performed: on one hand, the lipase/co-lipase assay, commonly described in the literature to study the digestion of lipid nanocarriers, and on the other hand, the lipolysis test using porcine pancreatic extract and the pH-stat apparatus. This pancreatic extract contains both the pancreatic lipase and carboxyl ester hydrolase (CEH) that permit to mimic in a biorelevant manner the duodenal digestive lipolysis. The test was performed by means of a pH-stat apparatus to work at constant pH, 5.5 or 6.25, representing respectively the fasted or fed state pH conditions. The evolution of all acylglycerol entities was monitored during the digestion by sampling the reaction vessel at different time points, until 60 min, and the lipid composition of the digest was analyzed by gas chromatography. SLN and NLC systems obtained with long-chain saturated acylglycerols were rapidly and completely digested by pancreatic enzymes. The pH-stat titration method appears to be a powerful technique to follow the digestibility of these solid lipid-based nanoparticles.

Intercalation of tetracycline into layered clay mineral material for drug delivery purposes

Abstract Intercalation of tetracycline (TC) into a pharmaceutical grade layered clay mineral was carried out, and the resultant complex was characterised. The intercalation of TC into the interlayer space of the clay took place via cation exchange resulting in an increase in d spacing of the clay and changes in the spectral bands of the NH+ vibration of the drug. Thermogravimetric analyses showed a delay in drug decomposition temperature as a consequence of drug intercalation. Release rate of the retained drug in simulated gingival fluid was compatible with the use of the complex in periodontal extended drug release systems.

A novel bioadhesive semisolid formulation containing chitosan and tetracycline/layered clay complexes for local delivery into periodontal pocket

Abstract An intrapocket non-conventional bioadhesive semisolid formulation based on tetracycline layered clay complexes and chitosan was developed to ensure extended drug release properties and adequate permanence time at the site of action. A Dohelert experimental design was used to discriminate among seven possible formulations, using viscosity as response variable. The formulation containing chitosan 2% (w/w) and complex (15% w/w) was selected as better candidate and was characterised for rheological behaviour, bioadhesive properties, microbicidal effect and drug delivery features. The formulation maintained the antibacterial activity of the drug against Streptococcus vestibularis, reaching a complete inactivation of bacterial cells after 24 h. The presence of the complex in the formulation not only did not induce any change in the intrinsic bioadhesive properties of chitosan, ensuring a good permanence time in the site of application but also resulted in drug release/wash away profiles compatible with a once a week administration of tetracycline HCl into the periodontal pocket.