Jing-Song Li

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.

Preparation and characterization of Ganoderma lucidum spores-loaded alginate microspheres by electrospraying.

Ganoderma lucidum spores (GLSs), popular functional food in preventive medicine, are susceptible to oxidative and acidic degradation during processing, storage and oral administration, resulting in the loss of sensory and nutritional qualities. The main objective of the study was to encapsulate the GLS in order to fully preserve the bioactivity of the ingredients as well as providing controlled and targeted delivery. Electrospraying was applied to prepare GLS-Alginate (GLS/A) micro beads in the current study. The size of GLS/A beads can be tailored by varying the applied voltage and drying processes. pH responsive release profiles of GLS/A beads were revealed from in vitro study in a simulated gastrointestinal environment: no release of GLS encapsulated beads in the simulated gastric fluid (pH of 1.8) was observed; while a rapid, size dependent release was found in the simulated intestinal solution (pH of 7.5). The release from smaller beads (e.g. 600 μm) was 1.5 times faster than that of larger beads (e.g. 2000 μm). In addition, the GLS release from freeze dried beads was almost 3 times faster than those of air and vacuum dried beads in the first 90 min. The present results illustrate the potential to protect GLS by encapsulation using electrospraying to achieve the controlled release of GLS ingredients. This will pave the way to develop effective GLS products with desirable bioactive components for healthcare applications.

Continuous micron-scaled rope engineering using a rotating multi-nozzle electrospinning emitter

Electrospinning (ES) enables simple production of fibers for broad applications (e.g., biomedical engineering, energy storage, and electronics). However, resulting structures are predominantly random; displaying significant disordered fiber entanglement, which inevitably gives rise to structural variations and reproducibility on the micron scale. Surface and structural features on this scale are critical for biomaterials, tissue engineering, and pharmaceutical sciences. In this letter, a modified ES technique using a rotating multi-nozzle emitter is developed and utilized to fabricate continuous micron-scaled polycaprolactone (PCL) ropes, providing control on fiber intercalation (twist) and structural order. Micron-scaled ropes comprising 312 twists per millimeter are generated, and rope diameter and pitch length are regulated using polymer concentration and process parameters. Electric field simulations confirm vector and distribution mechanisms, which influence fiber orientation and deposition during the process. The modified fabrication system provides much needed control on reproducibility and fiber entanglement which is crucial for electrospun biomedical materials.

Ganoderma lucidum polysaccharide loaded sodium alginate micro-particles prepared via electrospraying in controlled deposition environments

Ganoderma lucidum polysaccharide (GLP) is a functional food source deployed in preventative medicine. However, applications utilizing GLP are limited due to oxidative and acidic environmental damage. Advances in preserving GLP structure (and therefore function), in situ, will diversify their applications within biomedical fields (drug and antibacterial active delivery via the enteral route). In this study, GLP loaded sodium alginate (NaAlg) micro-particles (size range 225-355μm) were generated using the electrospray (ES) process. The loading capacity and encapsulation efficiency of GLP for composite particles (collected at different temperatures) were ∼23% and 71%, respectively. The collection substrate (CaCl2, 1-20w/v%) concentration was explored and preliminary findings indicated a 10w/v% solution to be optimal. The process was further modified by manipulating the collection environment temperature (∼25 to 50°C). Based on this, NaAlg/GLP micro-particles were engineered with variable surface morphologies (porous and crinkled), without effecting the chemical composition of either material (GLP and NaAlg). In-vitro release studies demonstrated pH responsive release rates. Modest release of GLP from micro-particles in simulated gastric fluid (pH ∼1.7) was observed, while rapid release was exhibited under simulated intestinal conditions (pH ∼7.4). Release of GLP from NaAlg beads was the greatest from samples prepared at elevated environmental temperatures. These findings demonstrate a facile route to fabricate GLP-NaAlg loaded micro-particles with various shapes, surface topographies and release characteristics via a one-step ES process.

Stable single device multi-pore electrospraying of polymeric microparticles via controlled electrostatic interactions

This work demonstrates a facile fabrication method to produce high throughput biodegradable microparticles (MPs) using a flute-like multi-pore emitter device in place of conventional single needle electrospraying capillaries. By manipulating the configuration of the emitter and the processing parameters, uniform microparticles are successfully sprayed in a single step for large-scale production. Furthermore, by manipulating individual spatial pore location various jet-bending interactions, which give rise to particle variations and irregularities, are overcome. Finally, findings correlate well with models reported by Hartman.

Essential Oil Bioactive Fibrous Membranes Prepared via Coaxial Electrospinning

A novel antimicrobial composite material was prepared by encapsulating orange essential oil (OEO) in zein prolamine (ZP) via the coaxial electrospinning (ES) technique. By manipulating process parameters, the morphological features of ZP/OEO fibers were modulated. Fine fibers with diameters ranging from 0.7 to 2.3 μm were obtained by regulating ZP solution concentration and process parameters during the ES process. Optimal loading capacity (LC) and encapsulation efficiency (EE) of OEO in fibrous ZP mats were determined to be 22.28% and 53.68%, respectively, and were achieved using a 35 w/v% ZP ES solution. The encapsulation of OEO was found to be reliant on ZP solution concentration (the enveloping medium). SEM analysis indicates the surface morphology of ZP/OEO electrospun fibers is dependent on ZP solution loading volume, with lower ZP concentrations yielding defective fibrous structures (for example, beaded and spindled-string like morphologies). Furthermore, this loading volume also influences OEO LC, EE, mat water contact angle and oil retention. CCK-8 assay and cell morphology assessment (HEK293T cells) indicate no significant change with electrospun ZP and ZP/OEO fibrous membranes over an 8 h period. Antimicrobial activity assessment using Escherichia coli, suggests composite nonwovens possess sterilization properties; elucidating potential application in active food packaging, food preservation and therefore sustainability.

Janus particle synthesis via aligned non-concentric angular nozzles and electrohydrodynamic co-flow for tunable drug release

A novel non-concentric, symmetrical spinneret possessing aligned nozzles with angular outlets was designed and manufactured. The device was used to synthesize Janus particles by atomizing co-flowing formulations at relatively high electric fields (up to ∼15 kV). By manipulating the nozzle outlet angle (θ), the maximum applied voltage permitting stable co-jetting was enhanced; enabling the production of finer droplets and, thus, microparticles. Furthermore, non-concentric co-flow, process optimization and stable atomization yielded Janus particles with distinct morphological features which were then used to demonstrate tunable drug release.

Investigation of Ice‐Assisted Sonication on the Microstructure and Chemical Quality of Ganoderma lucidum Spores

Ganoderma lucidum spores (GLS) are well known for disease treatment and vitality enhancement, and have been shown to contain a variety of bioactive components, such as polysaccharides and triterpenes. However, the resilient bilayer sporoderm structure of GLS restricts the release of bioactive components and limits its complete pharmacological effects. The current study was aimed to improve the quality of GLS by means of a customized sonication technique, particularly, the effect of sonication processing parameters on GLS-breaking efficiencies was investigated. Significant morphological changes, such as cracked, fractured, and disintegrated GLS were observed using scanning electron microscopy (SEM) after sonication treatment. The performance for breaking GLS sporoderm was obtained at ultrasonic power density of 23.7 W/cm(2) , duty cycle 100%, and 90-min processing time. Through the combination of sonication in an ice bath, sporoderm breaking efficiency can be further increased from 45% to almost 75%. FTIR analysis revealed an increase in bioactive components of polysaccharide, protein, and fatty acid from the sonication processed GLS when compared to ground spores available commercially. The current results indicated that the ice bath combined sonication method is more effective in delivering GLS ingredients and could be an economic technique for the production of high-quality broken sporoderm GLS.

Controlled Morphing of Microbubbles to Beaded Nanofibers via Electrically Forced Thin Film Stretching

Topography and microstructure engineering are rapidly evolving areas of importance for biomedical and pharmaceutical remits. Here, PVA (Polyvinyl alcohol) microbubbles (diameter range ~126 to 414 μm) were used to fabricate beaded (beads-on) nanofibers using an electrohydrodynamic atomization (EHDA) technique. Mean fiber diameter, inter-bead distance, and aspect ratio (AR) were investigated by regulating EHDA process parameters. PVA fibers (diameter range ~233 to 737 nm) were obtained possessing bead ARs in the range of ~10 to 56%. AR was used to modulate hydrophilicity and active release.