Sirolimus liposomal formulations : effects of Lipid Saturation/Surface charge on formulation stability and kinetics

• Main Author: Ong, Kelly Shi Hui
• Other Authors: Subbu S. Venkatraman
• Format: Final Year Project
• Language: English
• Published: 2018
• Subjects: DRNTU::Engineering::Materials
• Online Access: http://hdl.handle.net/10356/73739
• Institution: Nanyang Technological University

Sirolimus is a macrolide compound commonly used as an anti-proliferant, as a result of its inhibitory effect on the mTOR pathway. Despite its therapeutic potential, its application remains limited due to its low water solubility, low stability and reduced bioavailability within the body. Since the discovery of liposomes in the 1960s, drug delivery using these carriers have been actively studied, and widely used for the development of formulations to combat physiological pathologies. This project aims to develop 6 different types of sirolimus encapsulated liposomes, with variations in charges and lipid saturations. Formulations were extruded to produce small uni-lamillar vesicles (SUV) with high degree of mono-dispersity, and subsequently characterised based on their particle size, zeta potential, encapsulation efficiency (EE), drug loading (DL), storage stability as well as drug release kinetics over a period of 7 days. Except for the increase in hydrodynamic size, surface charges did not show significant effect on stability and release kinetics, while degree of saturation was highlighted to be the predominant factor, in affecting DL, stability and release kinetics of this study. DPPC, POPC, EPC, EPC-DOTAP and EPC-EPG all retained residual drug values of 88.4%±4.4%, 87.7%, 91%±1.4%, 85.6%±2.4%, 86.4%±7.6% respectively, while no residual drug was detected for SPC after 7 days. This results was attributed to the relatively high degree of unsaturation of 80.1%, as compared to the other formulations, causing a highly deformed bilayer, hence reducing the affinity of sirolimus to the lipid tails, enhancing release. Similarly, the trend of the release kinetics of sirolimus from the liposomes were also characterized by the gradient of the release curve, and was also found to be fastest in SPC > EPC ≈ EPC-EPG > DPPC ≈ POPC. This trend was similarly attributed to the increasing degree of unsaturation of lipid composition of the respective formulations. The objective of this project has been achieved in identifying the effects different lipids on drug delivery of sirolimus. This study has also value added the potential of using variable lipids composition to meet different requirements for therapeutic treatment.