Synthesis and characterisation of chitosan-coated thermosensitive liposomes for triggered release
File(s)
Author(s)
Wang, Wenxin
Type
Thesis
Abstract
Chitosan has been frequently utilized in many areas including drug delivery system, microcapsules, antibacterial agents, blood anti-coagulants and ophthalmology. Most of the liposomes modified by chitosan were used for oral, ocular and pulmonary delivery. Very little research has been undertaken to investigate the effect of chitosan coating on the characterization of liposomes for intravenous injection. HaT (Hyperthermia-Activated Cytotoxic) liposome was selected as the plain liposome formulation in this thesis, which has demonstrated faster release both in vitro and in vivo and superior ability to inhibit tumour growth and lower toxicity to healthy tissues than LTSL (Lysolipid-Containing Thermosensitive Liposome) after intravenous injection followed by hyperthermia. The aim of this thesis is to develop chitosan coated HaT liposomes encapsulated with calcein disodium salt and doxorubicin, respectively and compare their release characteristics with those of plain HaT liposomes. TEM images of plain liposomes and low, medium, and high MW chitaosan coated liposomes (freshly made and stored ones) were compared. Among all three concentrations (0.1%, 0.2% and 0.3% (w/w)), 0.1% (w/w) medium molecular weight chitosan coated HaT liposomes displayed the best overall performance with the lowest increase on both zeta potential and particle size after storage. Therefore, it was selected for the investigations of release property and shelf life of chitosan coated HaT liposomes. The coating of 0.1% (w/w) medium molecular weight chitosan can increase the stability of HaT liposomes encapsulated with calcein disodium salt or doxorubicin at 37 °C and enhance the shelf life of HaT liposomes both at room temperature and at 4 °C after storage. At 40 and 42 °C, the release percentages of chitosan coated liposomes were still substantial with a slight decrease compared to plain HaT liposomes. Finally, several commonly-used pharmaceutical kinetic models were selected to model the release curves of both calcein and doxorubicin encapsulated liposomes.
Version
Open Access
Date Issued
2023-05
Date Awarded
2023-12
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Luckham, Paul
Publisher Department
Chemical Engineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)