Development of a nanoporous and multilayer drug-delivery platform for medical implants.

Biodegradable polymers can be applied to a variety of implants for controlled and local drug delivery. The aim of this study is to develop a biodegradable and nanoporous polymeric platform for a wide spectrum of drug-eluting implants with special focus on stent-coating applications. It was synthesized by poly(DL-lactide-co-glycolide) (PLGA 65:35, PLGA 75:25) and polycaprolactone (PCL) in a multilayer configuration by means of a spin-coating technique. The antiplatelet drug dipyridamole was loaded into the surface nanopores of the platform. Surface characterization was made by atomic force microscopy (AFM) and spectroscopic ellipsometry (SE). Platelet adhesion and drug-release kinetic studies were then carried out. The study revealed that the multilayer films are highly nanoporous, whereas the single layers of PLGA are atomically smooth and spherulites are formed in PCL. Their nanoporosity (pore diameter, depth, density, surface roughness) can be tailored by tuning the growth parameters (eg, spinning speed, polymer concentration), essential for drug-delivery performance. The origin of pore formation may be attributed to the phase separation of polymer blends via the spinodal decomposition mechanism. SE studies revealed the structural characteristics, film thickness, and optical properties even of the single layers in the triple-layer construct, providing substantial information for drug loading and complement AFM findings. Platelet adhesion studies showed that the dipyridamole-loaded coatings inhibit platelet aggregation that is a prerequisite for clotting. Finally, the films exhibited sustained release profiles of dipyridamole over 70 days. These results indicate that the current multilayer phase therapeutic approach constitutes an effective drug-delivery platform for drug-eluting implants and especially for cardiovascular stent applications.

Evaluation of the functionality of biodegradable polymeric platforms for drug delivery systems

We present the development of a drug-loaded triple-layer platform consisting of thin film biodegradable polymers, in a properly designed form for the desired gradual degradation. Poly(dl-lactide-co-glycolide) (PLGA (65:35), PLGA (75:25)) and polycaprolactone (PCL) were grown by spin coating technique, to synthesize the platforms with the order PCL/PLGA (75:25)/PLGA (65:35) that determine their degradation rates. The outer PLGA (65:35) layer was loaded with dipyridamole, an antiplatelet drug. Spectroscopic ellipsometry (SE) in the Vis-far UV range was used to determine the nanostructure, as well as the content of the incorporated drug in the as-grown platforms. In situ and real-time SE measurements were carried out using a liquid cell for the dynamic evaluation of the fibrinogen and albumin protein adsorption processes. Atomic force microscopy studies justified the SE results concerning the nanopores formation in the polymeric platforms, and the dominant adsorption mechanisms of the proteins, which were defined by the drug incorporation in the platforms. © 2013 Elsevier B.V. All rights reserved.

Feasibility study of carbon nanotube microneedles for rapid transdermal drug delivery

We introduce a new approach for fabricating hollow microneedles using vertically-aligned carbon nanotubes (VA-CNTs) for rapid transdermal drug delivery. Here, we discuss the fabrication of the microneedles emphasizing the overall simplicity and flexibility of the method to allow for potential industrial application. By capitalizing on the nanoporosity of the CNT bundles, uncured polymer can be wicked into the needles ultimately creating a high strength composite of aligned nanotubes and polymer. Flow through the microneedles as well as in vitro penetration of the microneedles into swine skin is demonstrated. Furthermore, we present a trade study comparing the difficulty and complexity of the fabrication process of our CNT-polymer microneedles with other standard microneedle fabrication approaches. Copyright © Materials Research Society 2013.

Effect of size, composition, and morphology on magnetic performance: First-order reversal curves evaluation of iron oxide nanoparticles

© 2014 AIP Publishing LLC. Superparamagnetic nanoparticles are employed in a broad range of applications that demand detailed magnetic characterization for superior performance, e.g., in drug delivery or cancer treatment. Magnetic hysteresis measurements provide information on saturation magnetization and coercive force for bulk material but can be equivocal for particles having a broad size distribution. Here, first-order reversal curves (FORCs) are used to evaluate the effective magnetic particle size and interaction between equally sized magnetic iron oxide (Fe2O3) nanoparticles with three different morphologies: (i) pure Fe2O3, (ii) Janus-like, and (iii) core/shell Fe2O3/SiO2synthesized using flame technology. By characterizing the distribution in coercive force and interaction field from the FORC diagrams, we find that the presence of SiO2in the core/shell structures significantly reduces the average coercive force in comparison to the Janus-like Fe2O3/SiO2and pure Fe2O3particles. This is attributed to the reduction in the dipolar interaction between particles, which in turn reduces the effective magnetic particle size. Hence, FORC analysis allows for a finer distinction between equally sized Fe2O3particles with similar magnetic hysteresis curves that can significantly influence the final nanoparticle performance.

Potential of a cyclone prototype spacer to improve in vitro dry powder delivery.

PURPOSE: Low inspiratory force in patients with lung disease is associated with poor deagglomeration and high throat deposition when using dry powder inhalers (DPIs). The potential of two reverse flow cyclone prototypes as spacers for commercial carrier-based DPIs was investigated. METHODS: Cyclohaler®, Accuhaler® and Easyhaler® were tested with and without the spacers between 30 and 60 Lmin−1. Deposition of particles in the next generation impactor and within the devices was determined by high performance liquid chromatography. RESULTS: Reduced induction port deposition of the emitted particles from the cyclones was observed due to the high retention of the drug within the spacers (e.g. salbutamol sulphate (SS): 67.89 ± 6.51% at 30 Lmin−1 in Cheng 1). Fine particle fractions of aerosol as emitted from the cyclones were substantially higher than the DPIs alone. Moreover, the aerodynamic diameters of particles emitted from the cyclones were halved compared to the DPIs alone (e.g. SS from the Cyclohaler® at 4 kPa: 1.08 ± 0.05 μm vs. 3.00 ± 0.12 μm, with and without Cheng 2, respectively) and unaltered with increased flow rates. CONCLUSION: This work has shown the potential of employing a cyclone spacer for commercial carrier-based DPIs to improve inhaled drug delivery.

Acoustic radiation force of a Bessel beam on a porous sphere.

The possibility of using acoustic Bessel beams to produce an axial pulling force on porous particles is examined in an exact manner. The mathematical model utilizes the appropriate partial-wave expansion method in spherical coordinates, while Biot's model is used to describe the wave motion within the poroelastic medium. Of particular interest here is to examine the feasibility of using Bessel beams for (a) acoustic manipulation of fine porous particles and (b) suppression of particle resonances. To verify the viability of the technique, the radiation force and scattering form-function are calculated for aluminum and silica foams at various porosities. Inspection of the results has shown that acoustic manipulation of low porosity (<0.3) spheres is similar to that of solid elastic spheres, but this behavior significantly changes at higher porosities. Results have also shown a strong correlation between the backscattered form-function and the regions of negative radiation force. It has also been observed that the high-order resonances of the particle can be effectively suppressed by choosing the beam conical angle such that the acoustic contribution from that particular mode vanishes. This investigation may be helpful in the development of acoustic tweezers for manipulation of micro-porous drug delivery carrier and contrast agents.

Separating poroviscoelastic deformation mechanisms in hydrogels

Hydrogels have applications in drug delivery, mechanical actuation, and regenerative medicine. When hydrogels are deformed, load-relaxation arising from fluid flow - poroelasticity - and from rearrangement of the polymer network - viscoelasticity - is observed. The physical mechanisms are different in that poroelastic relaxation varies with experimental length-scale while viscoelastic does not. Here, we show that poroviscoelastic load-relaxation is the product of the two individual responses. The difference in length-scale dependence of the two mechanisms can be exploited to uniquely determine poroviscoelastic properties from simultaneous analysis of multi-scale indentation experiments, providing insight into hydrogel physical behavior. © 2013 American Institute of Physics.

Numerical modelling of chirality-Induced bi-Directional swimming of artificial flagella

Biomimetic micro-swimmers can be used for various medical applications, such as targeted drug delivery and micro-object (e.g. biological cells) manipulation, in lab-on-a-chip devices. Bacteria swim using a bundle of flagella (flexible hair-like structures) that form a rotating cork-screw of chiral shape. To mimic bacterial swimming, we employ a computational approach to design a bacterial (chirality-induced) swimmer whose chiral shape and rotational velocity can be controlled by an external magnetic field. In our model, we numerically solve the coupled governing equations that describe the system dynamics (i.e. solid mechanics, fluid dynamics and magnetostatics). We explore the swimming response as a function of the characteristic dimensionless parameters and put special emphasis on controlling the swimming direction. Our results provide fundamental physical insight on the chirality-induced propulsion, and it provides guidelines for the design of magnetic bi-directional micro-swimmers. © 2013 The Author(s) Published by the Royal Society. All rights reserved.

Dry oxidation and vacuum annealing treatments for tuning the wetting properties of carbon nanotube arrays.

In this article, we describe a simple method to reversibly tune the wetting properties of vertically aligned carbon nanotube (CNT) arrays. Here, CNT arrays are defined as densely packed multi-walled carbon nanotubes oriented perpendicular to the growth substrate as a result of a growth process by the standard thermal chemical vapor deposition (CVD) technique.(1,2) These CNT arrays are then exposed to vacuum annealing treatment to make them more hydrophobic or to dry oxidation treatment to render them more hydrophilic. The hydrophobic CNT arrays can be turned hydrophilic by exposing them to dry oxidation treatment, while the hydrophilic CNT arrays can be turned hydrophobic by exposing them to vacuum annealing treatment. Using a combination of both treatments, CNT arrays can be repeatedly switched between hydrophilic and hydrophobic.(2) Therefore, such combination show a very high potential in many industrial and consumer applications, including drug delivery system and high power density supercapacitors.(3-5) The key to vary the wettability of CNT arrays is to control the surface concentration of oxygen adsorbates. Basically oxygen adsorbates can be introduced by exposing the CNT arrays to any oxidation treatment. Here we use dry oxidation treatments, such as oxygen plasma and UV/ozone, to functionalize the surface of CNT with oxygenated functional groups. These oxygenated functional groups allow hydrogen bond between the surface of CNT and water molecules to form, rendering the CNT hydrophilic. To turn them hydrophobic, adsorbed oxygen must be removed from the surface of CNT. Here we employ vacuum annealing treatment to induce oxygen desorption process. CNT arrays with extremely low surface concentration of oxygen adsorbates exhibit a superhydrophobic behavior.

Mechanical characterisation of hydrogel materials

Interest in hydrogel materials is growing rapidly, due to the potential for hydrogel use in tissue engineering and drug delivery applications, and as coatings on medical devices. However, a key limitation with the use of hydrogel materials in many applications is their relatively poor mechanical properties compared with those of (less biocompatible) solid polymers. In this review, basic chemistry, microstructure and processing routes for common natural and synthetic hydrogel materials are explored first. Underlying structure-properties relationships for hydrogels are considered. A series of mechanical testing modalities suitable for hydrogel characterisation are next considered, including emerging test modalities, such as nanoindentation and atomic force microscopy (AFM) indentation. As the data analysis depends in part on the material's constitutive behaviour, a series of increasingly complex constitutive models will be examined, including elastic, viscoelastic and theories that explicitly treat the multiphasic poroelastic nature of hydrogel materials. Results from the existing literature on agar and polyacrylamide mechanical properties are compiled and compared, highlighting the challenges and uncertainties inherent in the process of gel mechanical characterisation. © 2014 Institute of Materials, Minerals and Mining and ASM International.