A guide to oral vaccination: Highlighting electrospraying as a promising manufacturing technique toward a successful oral vaccine development

Most vaccines approved by regulatory bodies are administered via intramuscular or subcutaneous injections and have shortcomings, such as the risk of needle-associated blood infections, pain and swelling at the injection site. Orally administered vaccines are of interest, as they elicit both systemic and mucosal immunities, in which mucosal immunity would neutralize the mucosa invading pathogen before the onset of an infection. Hence, oral vaccination can eliminate the injection associated adverse effects and enhance the person's compliance. Conventional approaches to manufacturing oral vaccines, such as coacervation, spray drying, and membrane emulsification, tend to alter the structural proteins in vaccines that result from high temperature, organic and toxic solvents during production. Electrohydrodynamic processes, specifically electrospraying, could solve these challenges, as it also modulates antigen release and has a high loading efficiency. This review will highlight the mucosal immunity and biological basis of the gastrointestinal immune system, different oral vaccine delivery approaches, and the application of electrospraying in vaccines development.     

Electrostatic micro- and nanoencapsulation and electroemulsification: A brief review

Electrospraying is a method of liquid atomization that utilizes electrical forces to overcome the surface tension force. The droplets obtained by electrospraying are charged and for certain modes can be nanometers in size. The charge and size of the droplets can be controlled to some extent by liquid flow rate and the voltage applied to the nozzle. In recent years, electrospraying was tested as a ‘bottom-up’ technology for building nanostructures from elementary components obtained from fine droplets or submicron jets after solvent evaporation, such as thin films, nanoparticles or nanofibres. It was also tested as a tool for the production of micro- and nanoemulsions and micro- and nanocapsules. Research in this field was aimed at developing new drug delivery systems or medicine production and application of this technique in cosmetic and food industries. Electro-encapsulation was also used as a tool for nanocomposite materials fabrication. The paper reviews various methods based on electrospraying used for electro-emulsification and micro- and nanoencapsulation. Numerous scientific and engineering contributions in this field are presented in this paper.     

Controlling the morphology and material characteristics of electrospray generated calcium alginate microhydrogels

Electrospraying nano- and micro-particle fabrication is a one-step, non-invasive process, which has application in encapsulating of thermosensitive functional, bioactive materials and cells and making microhydrogels. This study investigates the effect of various electrospraying process parameters on the characteristics of calcium alginate microhydrogel particles. The alginate solution concentration, CaCl₂ coagulation bath concentration, voltage, nozzle diameter, distance between nozzle and collecting bath (D), alginate delivery pressure (～H) were examined. The best droplet formation rate, in non-disperse dripping mode, was obtained at 8?kV using a 500?μm inner diameter nozzle tip, D?=?8?cm, H?=?20?cm. Morphology, swelling behaviour and texture analysis of the particles which were followed by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) confirmed that 1.5–2% (w/v) CaCl₂ was the desirable concentration for hydrogels formation. Particle size range between 267 and 1500?μm could be obtained by the drip feed mode compared with 2.3–6?μm by the pressure-assisted electrospray through a coaxial head.     

Fabrication of cross-linked alginate beads using electrospraying for adenovirus delivery

Cross-linked alginate beads containing adenovirus (Ad) were successfully fabricated using an electrospraying method to achieve the protection and release of Ad in a controlled manner. An aqueous alginate solution containing Ad was electrosprayed into an aqueous phase containing a cross-linking agent (calcium chloride) at different process variables (voltages, alginate concentrations, and flow rates). Alginate beads containing Ad were used for transduction of U343 glioma cells and the transduction efficiency of the alginate beads was measured by quantification of gene expression using a fluorescence-activated cell sorter at different time points. In vitro results of gene expression revealed that the Ad encapsulated in the alginate beads with 0.5 wt% of alginate concentration exhibited a high activity for a long period (over 7 days) and was released in a sustained manner from the alginate beads. The Ad-encapsulating alginate beads could be promising materials for local delivery of Ad at a high concentration into target sites.     

Electrosprayed Hydroxyapatite on Polymer Nanofibers to Differentiate Mesenchymal Stem Cells to Osteogenesis

Abstract

Electrospraying of hydroxyapatite (HA) nanoparticles onto the surface of polymer nanofibers provides a potentially novel substrate for the adhesion, proliferation and differentiation of mesenchymal stem cells (MSCs) into bone tissue regeneration. HA nanoparticles (4%) were electrosprayed on the surface of electrospun polycaprolactone (PCL) nanofibers (420 ± 15 nm) for bone tissue engineering. PCL/HA nanofibers were comparatively characterized with PCL/Collagen (275 ± 56 nm) nanofibers by FT-IR analysis to confirm the presence of HA. Fabricated PCL/HA and PCL/Collagen nanofibers and TCP (control) were used for the differentiation of equine MSC into osteogenic lineages in the presence of DMEM/F12 medium supplemented with β-glycerophosphate, ascorbic acid and dexamethasone. Cell proliferation and differentiation into an osteogenic lineage was evaluated by MTS assay, SEM observation, ALP activity, ARS staining, quantification of mineral deposition and expression of osteocalcin. Proliferation of MSCs increased significantly (P ? 0.05) up to 12% in PCL/Collagen (day 15) compared to PCL/HA nanofibrous substrate. ALP activity was increased 20% in PCL/HA by day 10 confirming the direction of osteogenic lineage from MSCs differentiation. PCL/HA stimulated an increased mineral secretion up to 26% by day 15 on ARS staining compared to PCL/Collagen nanofibers and showing cuboidal morphology by expressing osteocalcin. These results confirmed that the specifically fabricated PCL/HA composite nanofibrous substrate enhanced the differentiation of MSCs into osteogenesis.     

Influence of solvent mixtures on HPMCAS-celecoxib microparticles prepared by electrospraying

 Hypromellose acetate succinate (HPMCAS) microparticles containing the poorly-water soluble drug celecoxib (CEL) were prepared by electrospraying intended for oral drug delivery. Various solvent mixtures with different solubility for CEL and HPMCAS were used to induce changes in the polymer structural conformation of the microparticles. The performance of the prepared microparticles was evaluated by studying the solid state from, particle size and morphology, radial drug distribution and drug release. CEL was amorphous in all electrosprayed HPMCAS microparticles.The particle size and morphology was dependent on the solubility of HPMCAS in the solvent mixture used with poorer solvents resulting in smaller microparticles with rougher appearance. The CEL distribution on the particles surface was relatively homogeneous and similar for all microparticles. Drug release from the microparticles was observed at a higher rate depending on the solubility of HPMCAS in the solvent used for electrospraying, and in all cases an at least 4-fold higher rate was observed compared with the crystalline drug. Drug precipitation from the supersaturated solution was inhibited by HPMCAS for all microparticles based on its parachute effect while crystalline CEL did not reach supersaturation. This study demonstrated that electrospraying can be used to produce microparticles with tailored properties for pharmaceutical application by adjusting solvent selection.     

Electrohydrodynamics: A facile technique to fabricate drug delivery systems

Electrospinning and electrospraying are facile electrohydrodynamic fabrication methods that can generate drug delivery systems (DDS) through a one-step process. The nanostructured fiber and particle morphologies produced by these techniques offer tunable release kinetics applicable to diverse biomedical applications. Coaxial electrospinning/electrospraying, a relatively new technique of fabricating core-shell fibers/particles have added to the versatility of these DDS by affording a near zero-order drug release kinetics, dampening of burst release, and applicability to a wider range of bioactive agents. Controllable electrospinning/spraying of fibers and particles and subsequent drug release from these chiefly polymeric vehicles depends on well-defined solution and process parameters. The additional drug delivery capability from electrospun fibers can further enhance the material's functionality in tissue engineering applications. This review discusses the state-of-the-art of using electrohydrodynamic technique to generate nanofiber/particles as drug delivery devices.