Halloysite nanotubes as tools to improve the actual challenge of fixed doses combinations in tuberculosis treatment.

Halloysite nanotubes (HLNTs) were used as nanocarriers of the tuberculostatic agent isoniazid (INH), a BCS (Biopharmaceutics Classification System) class III drug. Self-assembling nanohybrids (INH-loaded HLNTs) with an average outer diameter of 90 nm and polydispersity index of 0.7 approximately, were obtained by spontaneous adsorption of INH molecules to HLNTs powder in aqueous medium. The nanohybrids were aimed to improve oral drug bioavailability and reduce physicochemical incompatibility of INH with other concomitantly administered tuberculostatic agents. In vitro drug release from INH-loaded HLNTs was successfully fitted to a diffusive kinetic law founded on the adsorption-desorption equilibrium between drug molecules in solution and solid inorganic excipients. INH-loaded HLNTs showed good in vitro biocompatibility toward Caco-2 cells at the concentrations studied (up to 1233 µg/mL), with improved cell proliferation. Permeability tests showed that INH transport across Caco-2 cellular membranes was greatly enhanced and fluorescent microscopy confirmed that the drug encapsulated into nanohybrid was effectively internalized by the cells. INH-loaded HLNTs enhanced stability of the drug in presence of other tuberculostatic agents, both in binary and quaternary combinations. It has been demonstrated that simple interaction between INH with HLNTs leads to drug permeability and stability improvements that could greatly facilitate the design of multiple drug dosage forms, an actual challenge in oral treatment of tuberculosis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.

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.

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

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.

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.

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.

Networking and rheology of concentrated clay suspensions "matured" in mineral medicinal water.

This work studied the influence of "maturation" conditions (time and agitation) on aggregation states, gel structure and rheological behaviour of a special kind of pharmaceutical semisolid products made of concentrated clay suspensions in mineral medicinal water. Maturation of the samples was carried out in distilled and sulphated mineral medicinal water, both in static conditions (without agitation) and with manual stirring once a week, during a maximum period of three months. At the measured pH interval (7.5-8.0), three-dimensional band-type networks resulting from face/face contacts were predominant in the laminar (disc-like) clay suspensions, whereas the fibrous (rod-like) particles formed micro-aggregates by van der Waals attractions. The high concentration of solids in the studied systems greatly determined their behaviour. Rod-like sepiolite particles tend to align the major axis in aggregates promoted by low shearing maturation, whereas aggregates of disc-like smectite particles did not have a preferential orientation and their complete swelling required long maturation time, being independent of stirring. Maturation of both kinds of suspensions resulted in improved rheological properties. Laminar clay suspensions became more structured with time, independently from static or dynamic maturation conditions, whereas for fibrous clay periodic agitation was also required. Rheological properties of the studied systems have been related to aggregation states and networking mechanisms, depending on the type of clay minerals constituents. Physical stability of the suspensions was not impaired by the specific composition of the Graena medicinal water.

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.