Against a backdrop of global antibiotic resistance and increasing awareness of the importance of the human microbiota, there has been resurgent interest in the potential use of bacteriophages for therapeutic purposes, known as phage therapy. A number of phage therapy phase I and II clinical trials have concluded, and shown phages don't present significant adverse safety concerns. These clinical trials used simple phage suspensions without any formulation and phage stability was of secondary concern. Phages have a limited stability in solution, and undergo a significant drop in phage titre during processing and storage which is unacceptable if phages are to become regulated pharmaceuticals, where stable dosage and well defined pharmacokinetics and pharmacodynamics are de rigueur. Animal studies have shown that the efficacy of phage therapy outcomes depend on the phage concentration (i.e. the dose) delivered at the site of infection, and their ability to target and kill bacteria, arresting bacterial growth and clearing the infection. In addition, in vitro and animal studies have shown the importance of using phage cocktails rather than single phage preparations to achieve better therapy outcomes. The in vivo reduction of phage concentration due to interactions with host antibodies or other clearance mechanisms may necessitate repeated dosing of phages, or sustained release approaches. Modelling of phage-bacterium population dynamics reinforces these points. Surprisingly little attention has been devoted to the effect of formulation on phage therapy outcomes, given the need for phage cocktails, where each phage within a cocktail may require significantly different formulation to retain a high enough infective dose. This review firstly looks at the clinical needs and challenges (informed through a review of key animal studies evaluating phage therapy) associated with treatment of acute and chronic infections and the drivers for phage encapsulation. An important driver for formulation and encapsulation is shelf life and storage of phage to ensure reproducible dosages. Other drivers include formulation of phage for encapsulation in micro- and nanoparticles for effective delivery, encapsulation in stimuli responsive systems for triggered controlled or sustained release at the targeted site of infection. Encapsulation of phage (e.g. in liposomes) may also be used to increase the circulation time of phage for treating systemic infections, for prophylactic treatment or to treat intracellular infections. We then proceed to document approaches used in the published literature on the formulation and stabilisation of phage for storage and encapsulation of bacteriophage in micro- and nanostructured materials using freeze drying (lyophilization), spray drying, in emulsions e.g. ointments, polymeric microparticles, nanoparticles and liposomes. As phage therapy moves forward towards Phase III clinical trials, the review concludes by looking at promising new approaches for micro- and nanoencapsulation of phages and how these may address gaps in the field.

This review provides an overview of major microengineering emulsification techniques for production of monodispersed droplets. The main emphasis has been put on membrane emulsification using Shirasu Porous Glass and microsieve membrane, microchannel emulsification using grooved-type and straight-through microchannel plates, microfluidic junctions and flow focusing microfluidic devices. Microfabrication methods for production of planar and 3D poly(dimethylsiloxane) devices, glass capillary microfluidic devices and single-crystal silicon microchannel array devices have been described including soft lithography, glass capillary pulling and microforging, hot embossing, anisotropic wet etching and deep reactive ion etching. In addition, fabrication methods for SPG and microseive membranes have been outlined, such as spinodal decomposition, reactive ion etching and ultraviolet LIGA (Lithography, Electroplating, and Moulding) process. The most widespread application of micromachined emulsification devices is in the synthesis of monodispersed particles and vesicles, such as polymeric particles, microgels, solid lipid particles, Janus particles, and functional vesicles (liposomes, polymersomes and colloidosomes). Glass capillary microfluidic devices are very suitable for production of core/shell drops of controllable shell thickness and multiple emulsions containing a controlled number of inner droplets and/or inner droplets of two or more distinct phases. Microchannel emulsification is a very promising technique for production of monodispersed droplets with droplet throughputs of up to 100 l h⁻¹.

Membrane emulsification (ME) is a relatively new technique for the highly controlled production of particulates. This review focuses on the recent developments in this area, ranging from the production of simple oil-in-water (O/W) or water-in-oil (W/O) emulsions to multiple emulsions of different types, solid-in-oil-in-water (S/O/W) dispersions, coherent solids (silica particles, solid lipid microspheres, solder metal powder) and structured solids (solid lipid microcarriers, gel microbeads, polymeric microspheres, core-shell microcapsules and hollow polymeric microparticles). Other emerging technologies that extend the capabilities into different membrane materials and operation methods (such as rotating membranes, repeated membrane extrusion of coarsely pre-emulsified feeds) are introduced. The results of experimental work carried out by cited researchers in the field together with those of the current authors are presented in a tabular form in a rigorous and systematic manner. These demonstrate a wide range of products that can be manufactured using different membrane approaches. Opportunities for creation of new and novel entities are highlighted for low throughput applications (medical diagnostics, healthcare) and for large-scale productions (consumer and personal products).

Microfluidics is an emerging and promising interdisciplinary technology which offers powerful platforms for precise production of novel functional materials (e.g., emulsion droplets, microcapsules, and nanoparticles as drug delivery vehicles- and drug molecules) as well as high-throughput analyses (e.g., bioassays, detection, and diagnostics). In particular, multiphase microfluidics is a rapidly growing technology and has beneficial applications in various fields including biomedicals, chemicals, and foods. In this review, we first describe the fundamentals and latest developments in multiphase microfluidics for producing biocompatible materials that are precisely controlled in size, shape, internal morphology and composition. We next describe some microfluidic applications that synthesize drug molecules, handle biological substances and biological units, and imitate biological organs. We also highlight and discuss design, applications and scale up of droplet- and flow-based microfluidic devices used for drug discovery and delivery.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).The effect of different binary solvent systems on the size and surface morphology of electrospun poly(ε-caprolactone) (PCL) fibres was investigated in this study. Chloroform (CF), dichloromethane (DCM), tetrahydrofuran (THF) and formic acid (FA) were used in mixtures with dimethyl sulfoxide (DMSO) in order to generate pores on the fibre surface, through a non-solvent induced phase separation mechanism. The production of porous, bead free fibres with an average diameter ranging from 1470 to 2270 nm was achieved using 12.5% w/v PCL in CF/DMSO solution with good/poor solvent ratios varying from 75-90% v/v at the applied voltage of 15 kV, a spinning distance of 20 cm, and the feed flow rate of 1 ml/h. DCM and THF were proven to be less suitable good solvents for the process due to the formation of a solid skin on the jet surface, caused by the limited diffusivity of the polymer molecules from the jet surface to the liquid core and its subsequent collapse. FA was found to be unsuitable due to its similar evaporation rate to DMSO. The pore formation was favoured at high good/poor solvent ratios, whereas, the production of fibres with ribbon cross sections or fibres with beads was more pronounced at low good/poor solvent ratios. Data fitting was used for the development of a second order polynomial equation, correlating the produced fibre average diameter to the solution parameters (conductivity, surface tension, and viscosity), for the given polymer and solvent systems, under the specific experimental conditions used in this study. The ternary mixture compositions that lead to the formation of porous fibres were mapped on a ternary graph

Microfluidic devices are promising tools for the production of monodispersed tuneable complex emulsions. This review highlights the advantages of microfluidics for the fabrication of emulsions and presents an overview of the microfluidic emulsification methods including two-step and single-step methods for the fabrication of high-order multiple emulsions (double, triple, quadruple and quintuple) and emulsions with multiple and/or multi-distinct inner cores. The microfluidic methods for the formation of multiple emulsion drops with ultra-thin middle phase, multi-compartment jets, and Janus and ternary drops composed of two or three distinct surface regions are also presented. Different configurations of microfluidic drop makers are covered, such as co-flow, T-junctions and flow focusing (both planar and three-dimensional (3D)). Furthermore, surface modifications of microfluidic channels and different modes of droplet generation are summarized. Non-confined microfluidic geometries used for buoyancy-driven drop generation and membrane integrated microfluidics are also discussed. The review includes parallelization and drop splitting strategies for scaling up microfluidic emulsification. The productivity of a single drop maker is typically 1 L/h, which requires combining drop makers into twodimensional (2D) and 3D assemblies fed from a single set of inlet ports through a network of distribution and collection channels.