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Ultrasound-responsive drug delivery systems have great potential for applications requiring stimulated release in vivo with a high degree of control over spatial and temporal location. In this study, systematic investigations were carried out to determine the effect of various ultrasound exposure parameters, in particular, output power, duty cycle and exposure time, on the release rate of a model drug (estradiol), encapsulated in poly DL-lactide-co-glycolide particles of different sizes prepared using electrohydrodynamic processing. The effect of ultrasound exposure on the degradation and surface morphology of the particles was also studied through optical and electron microscopy. There was found to be a positive correlation between drug release and each of the ultrasound parameters investigated, with output power having the most significant effect on both release rate and the morphology of the particles. The increase in surface porosity observed indicates that degradation may be attributed to cavitation phenomena.

A method for generating poly(lactic-co-glycolic acid) and polycaprolactone biodegradable particles of different size and shape using a jet generated in an electric field is elucidated. These particles are suitable for use as drug carriers and the method can be developed into a mass production route. The effect of different parameters such as applied voltage, collecting distance, flow rate and polymer concentration on inducing size and shape differences in these particles was studied. It was found that the flow rate, polymer concentration and collecting distance have a significant impact on the size of the generated particles and by changing the collecting distance a systematic reduction in the particle size by at least an order of magnitude (10microm-100nm) can be achieved. By using a high polymer concentration (30 wt. %) the shape and surface morphology of these particles can also be controlled from spherical to fibrous, and smooth to irregular, respectively, which presently is an interesting strategy and concept in drug delivery. This method is very useful as a one-step generator of different sizes of drug carriers with morphological variations.

Submicrometre size spheres prepared from biocompatible polymers are becoming increasingly popular in drug and gene delivery. This paper describes the preparation of polymeric spheres with a mean diameter of 0.4 μm with a polydispersivity index of 8%, using coaxial electrohydrodynamic atomization (CEHDA) microbubbling. An 18 wt.% solution of polymethylsilsesquioxane, a hydrophobic biocompatible polymer, was subjected to CEHDA microbubbling by passing air through the inner needle and polymer solution through the outer needle of a twin needle co-axial device, under the influence of an electric field. A parametric plot of the flow rate of air and the flow rate of polymer solution was constructed and used for systematic process control to reduce the diameter of the microspheres from micrometre size to submicrometre size. CEHDA is an excellent method for obtaining polymer microspheres. By studying the process in detail and mapping it, we can now demonstrate it can also be used to prepare submicrometre sized particles with the ability to control size and polydispersivity.

In this investigation, biodegradable polycaprolactone polymeric particles (300–4500 nm in diameter) were prepared by jetting a solution in an electric field. An extensive study has been carried out to determine how the size and size distribution of the particles generated can be controlled by systematically varying the polymer concentration in solution (and thereby its viscosity and electrical conductivity), and also the selected flow rate (2–50 µl min −1 ) and applied voltage (0–15 kV) during particle generation. Change in these parameters affects the mode of jetting, and within the stable cone-jet mode window, an increase in the applied voltage (approx. 15 kV) resulted in a reduction in particle size and this was more pronounced at high flow rates (such as; 30, 40 and 50 µl min −1 ) in the same region. The carrier particles were more polydisperse at the peripheral regions of the stable cone-jet mode, as defined in the applied voltage-flow rate parametric map. The effect of loading a drug on the particle size, size distribution and encapsulation efficiency was also studied. Release from drug-loaded particles was investigated using UV spectrophotometry over 45 days. This work demonstrates a powerful method of generating drug-loaded polymeric particles, with the ability to control size and polydispersivity, which has great potential in several categories of biotechnology requiring carrier particles, such as drug delivery and gene therapy.

The objective of this work was to produce drug-loaded nanometre- and micrometre-scale particles using a single-step process that provides control over particle size and size distribution. Co-axial electrohydrodynamic processing was used, at ambient temperature and pressure, with poly(lactic-co-glycolic acid) as the polymeric coating material and oestradiol as the encapsulated drug. The particle diameter was varied from less than 120 nm to a few micrometres, by simple methodical adjustments in the processing parameters (polymer concentration and applied voltage). In vitro studies were performed to determine the drug release profile from the particles during unassisted and ultrasound-stimulated degradation in simulated body fluid. An encapsulation efficiency of approximately 70% was achieved and release of the drug was sustained for a period of over 20 days. Exposing the particles to ultrasound (22.5 kHz) increased the rate of release by approximately 8 per cent. This processing method offers several advantages over conventional emulsification techniques for the preparation of drug-loaded particles. Most significantly, process efficiency and the drug's functionality are preserved, as complex multistep processing involving harsh solvents, other additives and elevated temperatures or pressures are avoided. Production rates of 10 12 particles min −1 can be achieved with a single pair of co-axial needles and the process is amenable to being scaled up by using multiple sets.

A poly (lactide-co-glycolide) (PLGA) implant was used to control the release profile of leuprolide acetate (LA) drug. The system is an in-situ polymeric precipitation system. And the formulation consisted of PLGA polymer, LA drug and N-methyl-2-pyrrolidon solvent with no additives. First, the formulation was injected into PBS solution for in-vitro studies and then it was administered to the animal models (female rats) for in-vivo release studies. The release profiles of leuprolide acetate were measured by UV spectrophotometry for a period of 28 days. The initial burst release of LA was 14% in in-vitro whereas it was 7% in in-vivo. In-vitro and in-vivo release profiles of LA had similar trends after 72 hours. However, the rate of LA release was slower in-vivo. This might be attributed to the limited diffusion process of solvent and the drug molecules. This could be due to presence of an additional pressure caused by the surrounding tissue and also the presence of small amount of water between cells in the subcutaneous site. Cross-section and surface of the implants were studied via scanning electron microscopy. Morphology of both in-vitro and in-vivo implants confirmed the release behaviours. No toxicity effects were reported in the histopathological assay. Furthermore, the pharmacological analysis showed more inactive ovaries due to release of LA.