Expanding the therapeutic potential of Statins by means of nanotechnology enabled drug delivery systems

Statins are effective lipid lowering agents traditionally used for the primary and secondary prevention of cardiovascular disease. Statins also exert a range of pleiotropic effects that make them attractive candidates for use in a wide range of disorders, in particular inflammatory and immune mediated conditions. However, the exploitation of such pleiotropic effects has been greatly hindered by poor bioavailability and adverse effects on muscles and the liver at higher doses. Nanotechnology is often suggested as the solution to this problem, as it enables an increased bioavailability of statins. Moreover, colloidal carriers can offer targeted drug delivery approaches that enable localised biological effects of statins, further reducing their potential for unwanted toxicity and adverse effects. This article reviews the available evidences for the increased potential of statin therapy when administered in nano-formulations such as nanocrystals, nanoparticles, liposomes, micelles and various nano-enabled devices. © 2014 Bentham Science Publishers

Wettability Modification of Nanomaterials by Low-Energy Electron Flux

Controllable modification of surface free energy and related properties (wettability, hygroscopicity, agglomeration, etc.) of powders allows both understanding of fine physical mechanism acting on nanoparticle surfaces and improvement of their key characteristics in a number of nanotechnology applications. In this work, we report on the method we developed for electron-induced surface energy and modification of basic, related properties of powders of quite different physical origins such as diamond and ZnO. The applied technique has afforded gradual tuning of the surface free energy, resulting in a wide range of wettability modulation. In ZnO nanomaterial, the wettability has been strongly modified, while for the diamond particles identical electron treatment leads to a weak variation of the same property. Detailed investigation into electron-modified wettability properties has been performed by the use of capillary rise method using a few probing liquids. Basic thermodynamic approaches have been applied to calculations of components of solid–liquid interaction energy. We show that defect-free, low-energy electron treatment technique strongly varies elementary interface interactions and may be used for the development of new technology in the field of nanomaterials

Dry Hybrid Lipid-Silica Microcapsules Engineered from Submicron Lipid Droplets and Nanoparticles as a Novel Delivery System for Poorly Soluble Drugs

We report on the fabrication and characterization of dry hybrid lipid-silica nanoparticle based microcapsules with an internal porous matrix structure for encapsulation of poorly soluble drugs, and their delivery properties (in vitro release and lipolysis and in vivo pharmacokinetics demonstrated for indomethacin as a model drug). Microcapsules were prepared by spray drying of Pickering o/w emulsions containing either negatively or positively charged lipophilic surfactant in the oil phase and hydrophilic silica nanoparticles in the aqueous phase. Effective microcapsule formation is critically dependent on the interfacial structure of the nanoparticle containing emulsions, which are in turn controlled by the surfactant charge and the nanoparticle to lipid ratio. Microcapsules (containing 50-85% oil) can be prepared with 10 times fewer silica nanoparticles when a droplet-nanoparticle charge neutralizing mechanism is operative. Cross-sectional SEM imaging has confirmed the internal porous matrix structure and identified pore sizes in the range 20-100 nm, which is in agreement with BET average pore diameters determined from gas adsorption experiments. Differential scanning calorimetry and X-ray diffraction analysis have confirmed that the model drug indomethacin remains in a noncrystalline form during storage under accelerated conditions (40 ì 75% RH). Dissolution studies revealed a 2-5-fold increase in dissolution efficiency and significantly reduced the time taken to achieve 50% of drug dissolution values (=2- or 10-fold) for indomethacin formulated as microcapsules in comparison to o/w submicron emulsions and pure drug, respectively. Orally dosed in vivo studies in rats have confirmed superior pharmacokinetics for the microcapsules. Specifically, the fasted state absolute bioavailability (F) was statistically higher (93.07 ᠵ.09%) (p < 0.05) than for aqueous suspension (53.54 ᠲ.91%) and o/w submicron emulsion (64.57 ᠲ.11%). The microcapsules also showed the highest maximum plasma concentration (Cmax) among the investigated formulations (p < 0.05). In vitro lipolysis showed statistically higher (p < 0.05) fasted digestion (75.8% after 5 min) and drug solubilization (98% after 5 min) in digestive products for microcapsules than o/w emulsions. The hybrid lipid-silica microcapsules improve oral absorption by enhancing lipolysis and drug dissolution.No Full Tex

A liposome-micelle-hybrid (LMH) oral delivery system for poorly water-soluble drugs: Enhancing solubilisation and intestinal transport.

A novel liposome-micelle-hybrid (LMH) carrier system was developed as a superior oral drug delivery platform compared to conventional liposome or micelle formulations. The optimal LMH system was engineered by encapsulating TPGS micelles in the aqueous core of liposomes and its efficacy for oral delivery was demonstrated using lovastatin (LOV) as a model poorly soluble drug with P-gp (permeability glycoprotein) limited intestinal absorption. LOV-LMH was characterised as unilamellar, spherical vesicles encapsulating micellar structures within the interior aqueous core and showing an average diameter below 200 nm. LMH demonstrated enhanced drug loading, water apparent solubility and extended/controlled release of LOV compared to conventional liposomes and micelles. LMH exhibited enhanced LOV absorption and transportation in a Caco-2 cell monolayer model of the intestine by inhibiting the P-gp transporter system compared to free LOV. The LMH system is a promising novel oral delivery approach for enhancing bioavailability of poorly water-soluble drugs, especially those presenting P-gp effluxes limited absorption

A simple and inexpensive enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine

Understanding the ecology of the gastrointestinal tract and the impact of the contents on the host mucosa is emerging as an important area for defining both wellness and susceptibility to disease. Targeted delivery of drugs to treat specific small intestinal disorders such as small bowel bacterial overgrowth and targeting molecules to interrogate or to deliver vaccines to the remote regions of the small intestine has proven difficult. There is an unmet need for methodologies to release probes/drugs to remote regions of the gastrointestinal tract in furthering our understanding of gut health and pathogenesis. In order to address this concern, we need to know how the regional delivery of a surrogate labeled test compound is handled and in turn, if delivered locally as a liquid or powder, the dynamics of its subsequent handling and metabolism. In the studies we report on in this paper, we chose 13C sodium acetate (13C-acetate), which is a stable isotope probe that once absorbed in the small intestine can be readily measured non-invasively by collection and analysis of 13CO2 in the breath. This would provide information of gastric emptying rates and an indication of the site of release and absorptive capacity. In a series of in vitro and in vivo pig experiments, we assessed the enteric-protective properties of a commercially available polymer EUDRAGIT® L100-55 on gelatin capsules and also on DRcaps®. Test results demonstrated that DRcaps® coated with EUDRAGIT® L100-55 possessed enhanced enteric-protective properties, particularly in vivo. These studies add to the body of knowledge regarding gastric emptying in pigs and also begin the process of gathering specifications for the design of a simple and cost-effective enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine.Darren S. Miller, Anne Michelle Parsons, John Bresland, Paul Herde, Duc Minh Pham, Angel Tan, Hung-Yao Hsu, Clive A. Prestidge, Tim Kuchel, Rezaul Begg, Syed Mahfuzul Aziz, Ross N. Butle

Anisotropic surface chemistry of crystalline pharmaceutical solids

The purpose of this study was to establish the link between the wetting behavior of crystalline pharmaceutical solids and the localized surface chemistry. A range of conventional wetting techniques were evaluated and compared with a novel experimental approach: sessile drop contact angle measurements on the individual facets of macroscopic (>1 cm) single crystals. Conventional measurement techniques for determining surface energetics such as capillary rise and sessile drops on powder compacts were found not to provide reliable results. When the macroscopic crystal approach was used, major differences for advancing contact angles, θa, of 0 waterwere observed—as low as 16° on facet (001) and as high as 68° on facet (010) of form I paracetamol. θa trends were in excellent agreement with X-ray photoelectron spectroscopy surface composition and known crystallographic structures, suggesting a direct relationship to the local surface chemistry. Inverse gas chromatography (IGC) was further used to probe the surface properties of milled and unmilled samples, as a function of particle size. IGC experiments confirmed that milling exposes the weakest attachment energy facet, with increasing dominance as particle size is reduced. The weakest attachment energy facet was also found to exhibit the highest θa for water and to be the 0 most hydrophobic facet. This anisotropic wetting behavior was established for a range of crystalline systems: paracetamol polymorphs, aspirin, and ibuprofen racemates. θa was 0 found to be very sensitive to the local surface chemistry. It is proposed that the hydrophilicity/hydrophobicity of facets reflects the presence of functional groups at surfaces to form hydrogen bonds with external molecules