O-5: Preparation of Multi-Component Drug Delivery Systems

Background: Despite global interest, the development of single step processes for the preparation of effective drug delivery systems still faces numerous challenges. There is great demand for processing methods that are efficient, flexible, scalable and economical for the generation of wide range of encapsulated structures. Over the past few decades, electrohydrodynamic (EHD) processing has received significant attention as a new method for the preparation of structures for therapeutic applications. The technique enables the production of nano or micro scale particles with a controlled size distribution. Encapsulation studies using coaxial EHD, whereby two or more concentric liquid jets are formed simultaneously, presentgreat potential for delivery systems i.e. carrier vehicles and multilayered capsules1. Often biodegradable and biocompatible polymers are used in delivery vehicles to encapsulate or entrap therapeutic agents. These materials are widely used as they allow sustained and controlled release of the encapsulated drug1. The current study utilises the EHD method combined with a novel tri-needle device for the preparation of multi-layered structures using different polymeric materials. The ability to fabricate such multilayered particles contributes to great advances in biomedical fields, in particular pharmaceutical applications. In the current study the utilization of this technology for the preparation of encapsulated drug delivery systems for the treatment of urinary tract infections will be presented. Recent cell studies will also be presented to validate this method as suitable for further loading of bioactive components. Materials and Methods: In the EHD technique, a liquid droplet is subjected to an electric field and the body of the liquid becomes charged. The electrostatic repulsion offsets the surface tension and a droplet forms at the end of the needle from which a fine jet emerges and breaks up to form smaller droplets1. During the process, solvent evaporates from the highly charged droplets leading to particle formation. The resulting particles’ morphology, size and dispersity are very much dependent on the processing conditions such as the applied voltage, liquid flow rate and also the distance between droplet formation and collection2. All these factors have been thoroughly investigated in this study. The liquid suspensions were prepared using three different biocompatible polymers of PLGA, PCL and PMSQ dissolved in Dimethyl carbonate, Dichloromethane and Ethanol, respectively, at various concentrations. A new device consisting of three separate needle, coaxially arranged, was used. The outer needle, central needle and inner needle were perfused simultaneously with PLGA, PCL and PMSQ solutions, respectively, at fixed flow rates. A high power voltage supply was connected between the needles and a grounded electrode. The jet and droplet formation processes were monitored using a high-speed camera. Stable nanoparticles, were collected in a petri dish filled with ethanol. A range of techniques were applied to characterize the nanostructures including transmission electron microscopy (TEM), scanning electron miscroscopy (SEM) with focused ion beam (FIB) milling, fourier transform infra-red (FTIR), nuclear magnetic resonance (NMR), dynamic light scattering (DLS) and UV-Vis spectroscopy. Results: The morphology, size and structure of the prepared nanoparticles that were studied using SEM and TEM are presented in 1. The figure, together with other results (not presented here), show that the processing route was successful as it resulted in the production of multi-layered nanoparticles with an average size of 350 nm (± 50 nm). The difference in density between the polymers used in this study allowed good visualization of the three distinct layers via TEM. All the results combined demonstrated the successful synthesis of mono-dispersed, spherical, multilayered particles using a single step process. Cell data showed the non-cytotoxic nature of the particles, making them further suitable for medical applications. Recent drug encapsulation studies will also be presented. In the current study the utilization of this technology for the preparation of encapsulated drug delivery systems for the treatment of urinary tract infections combined with a using gentamicine will be presented3. The capsules showed to kill the Entercoccus faecalis in a dose responsive manner. Conclusion: The capability of the electro-hydrodynamic process, in combination with a novel tri-needle device, for the preparation of drug delivery carriers was shown to be successful.