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Title: Development of thermal sensitive liposomes for targeted delivery and controlled release of drug
Author: Zhang, Xin
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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One of the clinical challenges in the treatment of diseases with a discrete distribution is the local delivery of active drugs without causing systemic side effects. Doxorubicin, an anti-cancer drug, is an example that may cause damage to patients due to its interaction with normal cells. Tissue plasminogen activator (tPA) is another active agent whose effectiveness is compromised due to its unselective effect on both healthy and pathological blood clots. Thermal sensitive liposome is a drug carrier that is not only able to entrap drug into it hydrophilic interior but can also release encapsulated agents upon mild hyperthermia. Currently, lysolipid-containing thermal sensitive liposome (LTSL) is a standard formulation due to its rapid release behaviour. However, concerns have been raised regarding the negative effect of lysolipid on LTSL stability that results in undesirable leakage of encapsulated drug in vivo at physiological temperature. Therefore, the first aim of the project was to develop a lysolipid-free thermal sensitive liposome (TSL) formulation. For this purpose, doxorubicin was adopted as a model drug. The amount of doxorubicin molecules encapsulated in TSL (0.0123 mg of doxorubicin per 1 mg of lipid) was 2 times the amount in the existing publications (0.05 mg of doxorubicin per 1 mg of lipid ). This was done by optimizing the incubation temperature (36oC for 1 hour) during preparation of TSL. When heated from room temperature to 42 oC, doxorubicin-encapsulated-TSLs release encapsulated doxorubicin molecules faster than their LTSL counterpart. This may result from a higher membrane-bound doxorubicin concentration in dox-TSLs. The second objective of the project was to develop a tPA-encapsulated TSL (tPA-TSL) formulation that can release encapsulated tPA molecules under hyperthermia condition. It has been demonstrated that the developed tPA-TSL was able to release encapsulated tPA upon 7 minute heating at 45oC. The release of tPA molecules was expected to result from irreversible destruction of liposome upon heating, as was demonstrated by reduction of particle size.
Supervisor: Xu, Xiao Yun; Luckham, Paul Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral