Ming-Wei Chang

A new method for the preparation of monoporous hollow microspheres.

The feasibility of producing a hollow microsphere with a single hole in its shell by coaxial electrohydrodynamic atomization (CEHDA) is demonstrated. Polymethylsilsesquioxane (PMSQ) was used as a model shell material encapsulating a core of a volatile liquid, perfluorohexane (PFH), which was subsequently evaporated to produce the hollow microspheres. The diameters of the microspheres and of the single surface pore were controlled by varying the flow rate of the components, the concentration of the PMSQ solution, and the applied voltage in the CEHDA process. The particles were characterized by scanning electron microscopy, and the ranges obtained were 275-860 nm for the microsphere diameter and 35-135 nm for the pore size. The process overcomes several of the key problems associated with existing methods of monoporous microsphere formation including removing the need for elevated temperatures, multiple processing steps, and the use of surfactants and other additives.

Controlling the thickness of hollow polymeric microspheres prepared by electrohydrodynamic atomization

In this study, the ability to control the shell thickness of hollow polymeric microspheres prepared using electrohydrodynamic processing at ambient temperature was investigated. Polymethylsilsesquioxane (PMSQ) was used as a model material for the microsphere shell encapsulating a core of liquid perfluorohexane (PFH). The microspheres were characterized by Fourier transform infrared spectroscopy and optical and electron microscopy, and the effects of the processing parameters (flow-rate ratio, polymer concentration and applied voltage) on the mean microsphere diameter (D) and shell thickness (t) were determined. It was found that the mean diameters of the hollow microspheres could be controlled in the range from 310 to 1000 nm while the corresponding mean shell thickness varied from 40 to 95 nm. The results indicate that the ratio D : t varied with polymer concentration, with the largest value of approximately 10 achieved with a solution containing 18 wt% of the polymer, while the smallest value (6.6) was obtained at 36 wt%. For polymer concentrations above 63 wt%, hollow microspheres could not be generated, but instead PMSQ fibres encapsulating PFH liquid were obtained.

Pharmaceutical and biomaterial engineering via electrohydrodynamic atomization technologies

Complex micro- and nano-structures enable crucial developments in the healthcare remit (e.g., pharmaceutical and biomaterial sciences). In recent times, several technologies have been developed and explored to address key healthcare challenges (e.g., advanced chemotherapy, biomedical diagnostics and tissue regeneration). Electrohydrodynamic atomization (EHDA) technologies are rapidly emerging as promising candidates to address these issues. The fundamental principle driving EHDA engineering relates to the action of an electric force (field) on flowing conducting medium (formulation) giving rise to a stable Taylor cone. Through careful optimization of process parameters, material properties and selection, nozzle and needle design, and collection substrate method, complex active micro- and nano-structures are engineered. This short review focuses on key selected recent and established advances in the field of pharmaceutical and biomaterial applications.

Modeling and fabrication of a microelectromechanical microwave switch

A microelectromechanical microwave switch manufactured by using a complementary metal oxide semiconductor (CMOS) post-process has been implemented. An equivalent circuit model is proposed to analyze the performance of the microwave switch. The components of the microwave switch consist of a coplanar waveguide (CPW), a suspended membrane and supported springs. The post-process requires only one wet etching to etch the sacrificial layer, and to release the suspended structures. Experimental results show that the switch has an insertion loss of -2dB at 50GHz and an isolation of -15dB at 50GHz. The driving voltage of the switch approximates to 19V.

A novel process for drug encapsulation using a liquid to vapour phase change material

Perfluorated hydrocarbons are widely used in the preparation of multifunctional capsules for medical and pharmaceutical applications. Their very low miscibility with organic solvents, however, represents a significant challenge for preparing stabilised droplets without using surfactants or other additives which have a deleterious effect upon capsule uniformity. The aims of this investigation were: firstly, to determine whether perfluorohexane (PFH) could be successfully encapsulated in a polymer, polymethylsilsesquioxane (PMSQ) in the absence of processing additives by using coaxial electrohydrodynamic atomisation (CEHDA); secondly, to assess the feasibility of controlling the content of the capsules by heating the suspension to the boiling point of the perfluorocarbon in order to achieve partial or total exchange of the encapsulated liquid. Both aims were successfully achieved. PFH-filled capsules were obtained viaCEHDA with a mean diameter of ∼200 nm and a polydispersity index of ∼30%. It was also found that capsules with a mean diameter of 37 nm and a polydispersity index of 23% could be obtained by altering the processing parameters, indicating this method is suitable for the preparation of both micro- and nanoscale capsules. The thickness of the polymeric coating was found to scale with the capsule outer diameter by a factor of ∼10. Encapsulation of a dye (Evans blue) was achieved by heating the capsules in the dye solution to vaporise the PFH core and enable inwards diffusion of the liquid. The rate of subsequent release of the dye was also measured viacolorimetry. This method may be useful in the preparation of multicomponent and multifunctional micro- and nanoparticles.

Microneedle Coating Techniques for Transdermal Drug Delivery

Drug administration via the transdermal route is an evolving field that provides an alternative to oral and parenteral routes of therapy. Several microneedle (MN) based approaches have been developed. Among these, coated MNs (typically where drug is deposited on MN tips) are a minimally invasive method to deliver drugs and vaccines through the skin. In this review, we describe several processes to coat MNs. These include dip coating, gas jet drying, spray coating, electrohydrodynamic atomisation (EHDA) based processes and piezoelectric inkjet printing. Examples of process mechanisms, conditions and tested formulations are provided. As these processes are independent techniques, modifications to facilitate MN coatings are elucidated. In summary, the outcomes and potential value for each technique provides opportunities to overcome formulation or dosage form limitations. While there are significant developments in solid degradable MNs, coated MNs (through the various techniques described) have potential to be utilized in personalized drug delivery via controlled deposition onto MN templates.

Stimulus-responsive liquids for encapsulation storage and controlled release of drugs from nano-shell capsules

Drug-delivery systems with a unique capability to respond to a given stimulus can improve therapeutic efficacy. However, development of such systems is currently heavily reliant on responsive polymeric materials and pursuing this singular strategy limits the potential for clinical translation. In this report, with a model system used for drug-release studies, we demonstrate a new strategy: how a temperature-responsive non-toxic, volatile liquid can be encapsulated and stored under ambient conditions and subsequently programmed for controlled drug release without relying on a smart polymer. When the stimulus temperature is reached, controlled encapsulation of different amounts of dye in the capsules is achieved and facilitates subsequent sustained release. With different ratios of the liquid (perfluorohexane): dye in the capsules, enhanced controlled release with real-time response is provided. Hence, our findings offer great potential for drug-delivery applications and provide new generic insights into the development of stimuli drug-release systems.

Magnetic-responsive microparticles with customized porosity for drug delivery

Several magnetic-polymer particle systems have been developed in recent times to facilitate improved targeting, localization and controlled delivery of active compounds. The main focus for such systems has centered on solid or core–shelled (non-porous) particles incorporating drug and magnetic features into individual polymeric carriers. In this study porous particles hosting drug (indomethacin) and magnetic Fe3O4 nanoparticles (NPs) were prepared, using a single needle one-step electrospraying technique via a non-solvent collection method. The resulting particles were characterized using scanning electron microscopy, energy dispersive spectra analysis, infrared spectroscopy, X-ray diffraction and Brunauer–Emmett–Teller specific area measurements. Analysis confirmed the incorporation of Fe3O4 NPs within the microspheres (∼20 μm in diameter), which could be further modified and tuned for porosity, magnetic response and thus release of incorporated active compounds. In vitro drug release for both porous and solid (non-porous) particle systems demonstrated high drug encapsulation efficiencies, ranging from ∼75% to 98%. Furthermore, the one-step synthesis process also suggested that the drug incorporated exists in an amorphous state, which is highly beneficial for drug absorption. Releases studies indicate a short drug burst period followed by a prolonged phase of dissolutive release. Based on mathematical fitting to both Higuchi and Korsmeyer–Peppas model, a release mechanism based on Fickian diffusion was confirmed. Through external alternating magnetic fields (AMF, 40 kHz), the drug release rate from magnetic-responsive microspheres was enhanced, facilitating drug release over the established Fickian process. This work demonstrates a versatile and efficient method for the development of drug-magnetic porous microparticles via a one-step electrospraying technique that enables controlled drug targeting, localization and tunable release.

Preparation of active 3D film patches via aligned fiber electrohydrodynamic (EHD) printing

The design, preparation and application of three-dimensional (3D) printed structures have gained appreciable interest in recent times, particularly for drug dosage development. In this study, the electrohydrodynamic (EHD) printing technique was developed to fabricate aligned-fiber antibiotic (tetracycline hydrochloride, TE-HCL) patches using polycaprolactone (PCL), polyvinyl pyrrolidone (PVP) and their composite system (PVP-PCL). Drug loaded 3D patches possessed perfectly aligned fibers giving rise to fibrous strut orientation, variable inter-strut pore size and controlled film width (via layering). The effect of operating parameters on fiber deposition and alignment were explored, and the impact of the film structure, composition and drug loading was evaluated. FTIR demonstrated successful TE-HCL encapsulation in aligned fibers. Patches prepared using PVP and TE-HCL displayed enhanced hydrophobicity. Tensile tests exhibited changes to mechanical properties arising from additive effects. Release of antibiotic from PCL-PVP dosage forms was shown over 5 days and was slower compared to pure PCL or PVP. The printed patch void size also influenced antibiotic release behavior. The EHDA printing technique provides an exciting opportunity to tailor dosage forms in a single-step with minimal excipients and operations. These developments are crucial to meet demands where dosage forms cannot be manufactured rapidly or when a personalized approach is required.

Electrically atomised formulations of timolol maleate for direct and on-demand ocular lens coatings

Graphical abstract Figure. No Caption available. Abstract Advances in nanotechnology have enabled solutions for challenging drug delivery targets. While the eye presents numerous emerging opportunities for delivery, analysis and sensing; issues persist for conventional applications. This includes liquid phase formulation localisation on the ocular surface once administered as formulated eye‐drops; with the vast majority of dosage (>90%) escaping from the administered site due to tear production and various drainage mechanisms. The work presented here demonstrates a single needle electrohydrodynamic (EHD) engineering process to nano‐coat (as an on demand and controllable fiber depositing method) the surface of multiple contact lenses rendering formulations to be stationary on the lens and at the bio‐interface. The coating process was operational based on ejected droplet charge and glaucoma drug timolol maleate (TM) was used to demonstrate surface coating optimisation, bio‐surface permeation properties (flux, using a bovine model) and various kinetic models thereafter. Polymers PVP, PNIPAM and PVP:PNIPAM (50:50%w/w) were used to encapsulate the active. Nano‐fibrous and particulate samples were characterised using SEM, FTIR, DSC and TGA to confirm structural and thermal stability of surface coated formulations. More than 52% of nano‐structured coatings (for all formulations) were <200 nm in diameter. In vitro studies show coatings to exhibit biphasic release profiles; an initial burst release followed by sustained release; with TM‐loaded PNIPAM coating releasing most drug after 24 h (89.8%). Kinetic modelling (Higuchi, Korsmeyer‐Peppas) was indicative of quasi‐Fickian diffusion whilst biological evaluation demonstrates adequate ocular tolerability. Results from permeation studies indicate coated lenses are ideal to reduce dosing regimen, which in turn will reduce systemic drug absorption. Florescent microscopy demonstrated probe and probe embedded coating behaviour from lens surface in vitro. The multiple lens surface coating method demonstrates sustained drug release yielding promising results; suggesting both novel device and method to enhance drug activity at the eyes surface which will reduce formulation drainage.