AbstractIn the past two decades, liposomes have been employed extensively as vehicles to modify and enhance the delivery of drugs, vaccines, and biomolecules. This highly versatile drug delivery system lends itself to a plethora of applications, providing both safety and efficacy. Within this thesis, the potential of liposomes to deliver challenging drugs has been explored, including the co-delivery of drugs of divergent solubility and an anti-respiratory syncytial virus (RSV) peptide.
Prior to the formulation development, the HPLC based method for simultaneous analysis of the drugs metformin HCl and glipizide was developed and validated. The formulation development initially considered the production of multi-lamellar vesicles using the conventional thin film hydration method, where the effect of lipid chain length and cholesterol content on liposome attributes was considered. After optimising the concentration of cholesterol, the capacity of
liposomes to load drugs was determined by a pilot escalation study for both the drugs. The synergistic effect of drugs on in-vitro drug release was studied using USP-IV dissolution apparatus. Furthermore, the similar composition of lipids was used to prepare liposomes with the emerging technique, microfluidics. Here, for the first time, simultaneous co-encapsulation of hydrophilic and lipophilic drug was demonstrated. Following the optimisation of microfluidics process parameters necessary for the production of small unilamellar liposomes with narrow polydispersity index (PDI), the effect of single or co-drug encapsulation on particle characteristics and drug encapsulation was investigated, with a subsequent pilot drug escalation study to determine the drug loading capacity of liposomes produced by microfluidics. Finally, in-vitro studies were performed to study the synergistic effect of simultaneously co-encapsulated drugs. Also, the potential of the 1,2-disteroyl-sn-glycerophosphocholine (DSPC): cholesterol formulation as a carrier of anti-RSV protein and the empty formulation itself as anti-RSV agent were investigated using bio-analytical techniques.
The co-encapsulation of drugs of divergent solubility was achieved by both the conventional thin film hydration and the emerging microfluidics technology. However, microfluidics proved advantageous with regards to time required for liposome production, one-step production of small unilamellar vesicles (SUV), narrow PDI and effective drug encapsulation with lower amounts of lipids. The liposomes of DSPC: cholesterol were also discovered to be a potential
carrier of anti-RSV peptide, as well as potential anti-RSV agent itself, compared with the reported gold nanoparticles (GNPs).
|Date of Award||23 Jun 2017|
|Supervisor||Daniel Kirby (Supervisor)|
- thin-film hydration