Andrew J. Urquhart

High throughput surface characterization : a review of a new tool for screening prospective biomedical material arrays

The application of high throughput surface characterization (HTSC) to the analysis of polymeric biomaterial libraries is an important advancement for the discovery and development of new biomedical materials and is the focus of this review. The potential for HTSC to identify structure/activity relationships for large libraries of materials can be utilized to accelerate materials discovery as well as providing insight into the underlying biological-material interactions. Furthermore, the correlations identified between surface chemical structure and cellular behavior could not have been predicted by a rational design approach based simply on review of bulk structure, which demonstrates the importance of HTSC in the assessment of cell-material and cell-biomolecular interactions that are dependent on surface properties.

Influence of the plasma sheath on plasma polymer deposition in advance of a mask and down pores

Plasma species that form plasma polymer deposits readily penetrate through small openings and are therefore well suited to coat the interior of porous objects. Here, we show how the size of the cross section of square channels influences the penetration of active species from a hexane plasma and how it affects the formation of surface chemical gradients in the interior of these model pores. WCA mapping and ToF-SIMS imaging are used to visualize the plasma polymer deposit in the interior of the model pores and demonstrate that a strong dependence of the wettability gradient profile only exists up to a channel cross section of about 1 mm. XPS data allow us to calculate a deposition rate of plasma polymerized hexane (ppHex) at discrete positions on the surface and show that the deposition rate of ppHex is reduced by the presence of the mask up to a distance of 16 mm in advance of the channel opening. A strong dependence of the ppHex deposition rate on the cross-section of the channels is found within the first 2 mm in front of the pore opening. An estimation of the sheath thickness suggests that this effect can be attributed to the plasma sheath that perturbs the plasma in front of the pores. Plasma mass spectrometry allows us to identify the nature of the plasma species penetrating from the plasma through the pores and shows that no negatively charged ions are able to penetrate through the small channels. Neutral and positively charged species penetrate several millimeters down the channels and both species are therefore likely to contribute to the formation of the deposit on the sample. In addition, the formation of positively charged higher molecular mass hexane fragments is observed in the gas phase, demonstrating the likelihood of neutral-positive reactions in the plasma.

Lipid-like Self-Assembling Peptide Nanovesicles for Drug Delivery

Amphiphilic self-assembling peptides are functional materials, which, depending on the amino acid sequence, the peptide length, and the physicochemical conditions, form a variety of nanostructures including nanovesicles, nanotubes, and nanovalves. We designed lipid-like peptides with an aspartic acid or lysine hydrophilic head and a hydrophobic tail composed of six alanines (i.e., ac-A6K-CONH2, KA6-CONH2, ac-A6D-COOH, and DA6-COOH). The resulting novel peptides have a length similar to biological lipids and form nanovesicles at physiological conditions. AFM microscopy and light scattering analyses of the positively charged lipid-like ac-A6K-CONH2, KA6-CONH2 peptide formulations showed individual nanovesicles. The negatively charged ac-A6D-COOH and DA6-COOH peptides self-assembled into nanovesicles that formed clusters that upon drying were organized into necklace-like formations of nanovesicles. Encapsulation of probe molecules and release studies through the peptide bilayer suggest that peptide nanovesicles may be good candidates for sustained release of pharmaceutically active hydrophilic and hydrophobic compounds. Lipid-like peptide nanovesicles represent a paradigm shifting system that may complement liposomes for the delivery of diagnostic and therapeutic agents.

Encapsulation of Water Insoluble Drugs in Mesoporous Silica Nanoparticles using Supercritical Carbon Dioxide

Mesoporous silica nanoparticles MCM – 41 were synthesized with two dimensional hexagonal p6mm symmetry, high specific surface area(~ 980m2/g) narrow pore size and an average particle size of 186 nm. The produced nanoparticles were used to encapsulate carbamazepine through a supercritical carbon dioxide process combined with various organic solvents. Supercritical processing was found to provide increased drug encapsulation. The loaded MCM - 41 nanoparticles were analyzed using X–ray diffraction and differential scanning calorimetry (DSC) to investigate the crystalline state of the encapsulated carbamazepine and it was found to be dependent on the nature of the organic solvent. Carbamazepine showed increased dissolution rates under sink conditions. Viability studies of Caco – 2 cells demonstrated negligible cytotoxicity for the MCM–41 nanoparticles.

Preparation and characterization of ibuprofen solid lipid nanoparticles with enhanced solubility

Solid lipid nanoparticles (SLNs) loaded with ibuprofen (IBU) were prepared by solvent-free high-pressure homogenization (HPH). The produced SLNs consisted of stearic acid, triluarin or tripalmitin as lipid matrixes and various stabilizers. The produced empty and IBU-loaded SLNs were characterized for particle size stability over 8 months. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were implemented to characterize the IBU state of freeze-dried SLNs. IBU was found to be in both amorphous and crystalline form within the lipid matrix. The lyophilized powders showed increased dissolution rates for IBU depending on the lipid nature. SLNs were incubated in Caco-2 cells for 24 h showing negligible cell cytotoxicity up to 15 mg/mL.

ToF-SIMS analysis of dexamethasone distribution in the isolated perfused eye

PURPOSE To illustrate the ability of time-of-flight secondary ion mass spectrometry (ToF-SIMS) to characterize and demonstrate the spatial distribution of dexamethasone within ocular tissues. METHODS Dexamethasone sodium phosphate was administrated to perfused and nonperfused ovine eyes via intravitreal injections. The vitreous humor, the lens, and the retina of the eyes were then removed and divided into front, middle, and back sections. ToF-SIMS analysis was performed on each cross-section of the vitreous humor using Bi(3+) cluster source and images of drug distribution within the sections generated. RESULTS In the positive ion spectra, four key drug fragment peaks were identified and in the negative ion spectra, one key drug peak was identified. All five important drug peaks were successfully imaged in each tissue section and their distribution within the section illustrated. The drug was shown in the nonliving eye to move by diffusion alone, whereas in the living eye the drug was shown to distribute faster within the vitreous and penetrate through to the back of the retina and also into the lens. CONCLUSIONS The results illustrate the ability of ToF-SIMS to characterize and provide spatial information about drug distribution within ocular tissues. Key differences in drug movement through the vitreous humor, toward both the anterior and the posterior tissues, in the living eye and the nonliving ovine eye were demonstrated, showing that dexamethasone sodium phosphate distribution through the vitreous is not determined by diffusion alone.

A pharmacokinetic study of a combination of beta adrenoreceptor antagonists – In the isolated perfused ovine eye

The treatment of posterior eye diseases, such as diabetic retinopathy and age-related macular degeneration, is of growing interest as the number of people affected by these conditions continues to rise. This study utilises the methods of cassette dosing and the perfused ovine eye model - to reduce animal usage and therefore animal time - to show that for a series of beta adrenoreceptor antagonists, lipophilicity is a key physicochemical property that governs drug distribution within the eye. Following intravitreal injection, lipophilic beta adrenoreceptor antagonists penetrate to the posterior eye, where they bind to the choroid and reside in the retina at greater concentrations than more hydrophilic beta adrenoreceptor antagonists, which preferentially penetrate to the anterior eye.

Surface-mediated two-dimensional growth of the pharmaceutical carbamazepine.

Scanning tunneling microscopy (STM) has become a staple surface microscopy technique for a number of research fields ranging from semiconductor research to heterogeneous catalysis. Pharmaceutical compounds, however, remain largely unstudied. Here we report the first STM study of carbamazepine (CBZ), an anti-epileptic drug, on Au(111) and Cu(111) surfaces. The analysis reveals that CBZ adopts unusual chiral molecular architectures on both metals. These previously unreported structures, which are strikingly different from CBZ packing arrangements observed in 3D crystal structures, indicate that the main molecular architecture is driven by a combination of CBZ intermolecular hydrogen bonding and metal-CBZ interactions. Comparison of the 2D molecular structures reveals large differences in local geometry and packing density that are dependent on the nature of the metal surface. These results have implications for the potential role of metal surfaces as heteronuclei or templating agents for controlling polymorph formation, which continues to be a problem for many compounds in the pharmaceutical industry including CBZ.

ToF-SIMS analysis of ocular tissues reveals biochemical differentiation and drug distribution

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to obtain mass spectra from three ocular tissues, the lens, the vitreous and the retina. All three tissues were extracted from control ovine eyes and ovine eyes treated with model drug. To identify variations in surface biochemistry of each ocular tissue, principal component analysis (PCA) was applied to ToF-SIMS data. Interesting physiological differences in Na(+) and K(+) distribution were shown across the three tissue types, with other elements including Ca(2+) and Fe(2+) distribution also detected. In addition to the identification of small molecules and smaller molecular fragments, larger molecules such as phosphocholine were also detected. The ToF-SIMS data were also used to identify the presence of a model drug compound (amitriptyline--chosen as a generic drug structure) within all three ocular tissues, with model drug detected predominantly across the vitreous tissue samples. This study demonstrates that PCA can be successfully applied to ToF-SIMS data from different ocular tissues and highlights the potential of coupling multivariate statistics with surface analytical techniques to gain a greater understanding of the biochemical composition of tissues and the distribution of pharmaceutically active small molecules within these tissues.

Investigation of Acrylic Acid at High Pressure Using Neutron Diffraction

This article details the exploration of perdeuterated acrylic acid at high pressure using neutron diffraction. The structural changes that occur in acrylic acid-d4 are followed via diffraction and rationalized using the Pixel method. Acrylic acid undergoes a reconstructive phase transition to a new phase at ∼0.8 GPa and remains molecular to 7.2 GPa before polymerizing on decompression to ambient pressure. The resulting product is analyzed via Raman and FT-IR spectroscopy and differential scanning calorimetry and found to possess a different molecular structure compared with polymers produced via traditional routes.