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

摘要

In this thesis, the capability of the electrohydrodynamic atomization (EHDA)udprocess for preparing drug delivery carriers consisting of biodegradable polymericudparticles with different sizes and shapes was explored. The first part of the thesisuddescribes a detailed investigation of how the size, morphology and shape of theudparticles generated can be controlled through the operating parameters; specificallyudthe flow rate, applied voltage and the properties of the solutions. Diameter and shapeudof the particles were greatly influenced by viscosity and applied voltage. The meanudsize of the particles changed from 340 nm to 4.4 μm as the viscosity increased fromud2.5 mPa s to 11 mPa s. Also, using more concentrated polymer solution (30 wt%)udand higher applied voltage (above 14 kV) were found to be ideal for promoting chainudentanglement and shape transition from spherical to oblong to a more needle-likeudshape. Estradiol-loaded micro and nanoparticles were produced with mean sizesudranging from 100 nm to 4.5 μm with an encapsulation efficiency ranging betweenud65% to 75%. The in vitro drug release profiles of the particles started with an initialudshort burst phase and followed by a longer period characterised by a lower releaseudrate. Two strategies were developed to tailor these profiles. First, ultrasound wasudexplored as a non-invasive method to stimulate “on demand” drug release fromudcarrier particles. Systematic investigations were carried out to determine the effect ofudvarious ultrasound exposure parameters on the release rate in particular outputudpower, duty cycle and exposure time. These three exposure parameters were seen toudhave a significant enhancing effect upon the drug release rate (up to 14%). Theudsecond strategy explored was coating the surface of the particles with chitosan andudgelatin. This enabled control and reduction of the prominence ‘burst release’ phaseudwithout affecting other parts of the release profile. Coating the particle surface withud1 wt% chitosan solution considerably reduces the initial release by 62%, 60% andud42% for PLGA 2 wt%, 5 wt% and 10 wt%, respectivly in the first 72 hours Thisudwork demonstrates a powerful method of generating micro and nano drug-loadedudpolymeric particles, with modified release behaviour and with control over the initialudrelease.