Novel chemical and physical approaches for sustainable drug release from biodegradable electrospun nanofibres
Creators: name: Jalvandi, Javid
Publisher: name: RMIT University
Year: 2024
Subjects: classificationCode: 320599
subject: Medical biochemistry and metabolomics not elsewhere classified
classificationCode: 401413
subject: Textile technology
classificationCode: 401805
subject: Nanofabrication, growth and self assembly
classificationCode: 401807
subject: Nanomaterials

description: Drug delivery systems have great importance for medical application. There have been wide ranging studies on drug delivery systems up to date. Among them, the fabrication of nano-size drug delivery systems and utilizing them for the effective and controlled delivery of drugs is an emerging and promising field of research. Various studies on drug nanocarriers have been reported such as electrospun nanofibres and nanoparticles; however the main drawback of nearly all is that they lack the control over the release profile of the drug. The burst release of drug is the main issue reported seen in almost all cases. <br><br>The purpose of this work was to develop composite biodegradable nanofibres fabricated using the electrospinning technique with different chemical and physical approaches to slow down the fast burst release and control the release profile. This thesis exploits electrospun biodegradable nanofibres as the main carrier of drug/nanoparticles complexes and drug-conjugated polymers to obtain sustained release of drug. To achieve this, mesoporous silica nanoparticles (MSN) acting as a nano sized vehicle as a drug delivery system were first investigated. Then, the adsorption of the drug into mesoporous structure was fabricated and characterized. The drug loaded nanoparticles were confined to the core section of core-shell nanofibres by means of co-axial electrospinning. This method provided a reduction in burst release compared to regular drugnanofibres and a sustained release.<br><br> In the next stage, a model drug was covalently bound to the silica nanoparticles via a cleavable bond. In the first two experiments the MSN was used as nanocarrier of levofloxacin (LVF). LVF-MSN complexes were prepared using different approaches. In the first approach, LVF was physically adsorbed into the porous structure of the MSN. The LVF-MSN complex was then confined into the core section of core-shell PCL nanofibres. In the second approach, LVF was covalently bound to MSN via a cleavable bond which can be hydrolysed in release buffered solution. LVF-MSN conjugated complexes were then blended with PCL and composite nanofibres fabricated by electrospinning techniques.<br><br> In the final experiment, polyvinyl alcohol (PVA) was used as the main polymer matrix. The purpose of this experiment was to achieve sustained release of drug from a fast dissolving polymer. To achieve this goal, chitosan (CS) as a naturally derived polymer, was used as main carrier of LVF. LVF was covalently bound to the chitosan via a cleavable bond. The conjugated LVF-CS was blended into a PVA solution and electrospun. In vitro drug release profiles were measured in all cases. The research confirmed that release profiles can be affected by chemical and physical factors. First, the core-shell structure of nanofibres can reduce burst release behaviour. This can be further reduced by employing LVF encapsulated MSN. Second, cleavable bonds between LVF and carriers played a significant role in reducing the burst release behaviour; where LVF was released first by hydrolysis of the cleavable bonds between LVF and carriers, and then from the polymer matrix.<br><br> The results indicated that burst release of the drug significantly reduced in all studies and the release profiles of drug were all slowed. The physical and chemical approaches used in the thesis to fabricate drug loaded composite nanofibres showed slow release of LVF with sustained release over a sustained period of time.<br>