Electric jet assisted production of micro and nano-scale particles as drug delivery carriers

In this thesis, the capability of the electrohydrodynamic atomization (EHDA) process for preparing drug delivery carriers consisting of biodegradable polymeric particles with different sizes and shapes was explored. The first part of the thesis describes a detailed investigation of how the size, morphology and shape of the particles generated can be controlled through the operating parameters; specifically the flow rate, applied voltage and the properties of the solutions. Diameter and shape of the particles were greatly influenced by viscosity and applied voltage. The mean size of the particles changed from 340 nm to 4.4 μm as the viscosity increased from 2.5 mPa s to 11 mPa s. Also, using more concentrated polymer solution (30 wt%) and higher applied voltage (above 14 kV) were found to be ideal for promoting chain entanglement and shape transition from spherical to oblong to a more needle-like shape. Estradiol-loaded micro and nanoparticles were produced with mean sizes ranging from 100 nm to 4.5 μm with an encapsulation efficiency ranging between 65% to 75%. The in vitro drug release profiles of the particles started with an initial short burst phase and followed by a longer period characterised by a lower release rate. Two strategies were developed to tailor these profiles. First, ultrasound was explored as a non-invasive method to stimulate “on demand” drug release from carrier particles. Systematic investigations were carried out to determine the effect of various ultrasound exposure parameters on the release rate in particular output power, duty cycle and exposure time. These three exposure parameters were seen to have a significant enhancing effect upon the drug release rate (up to 14%). The second strategy explored was coating the surface of the particles with chitosan and gelatin. This enabled control and reduction of the prominence ‘burst release’ phase without affecting other parts of the release profile. Coating the particle surface with 1 wt% chitosan solution considerably reduces the initial release by 62%, 60% and 42% for PLGA 2 wt%, 5 wt% and 10 wt%, respectivly in the first 72 hours This work demonstrates a powerful method of generating micro and nano drug-loaded polymeric particles, with modified release behaviour and with control over the initial release