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Title: Investigation into deformable vesicles for topical drug delivery
Author: Lanzilotti, Pierfrancesco
ISNI:       0000 0004 7231 3911
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2018
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The applicability of deformable vesicles for topical drug delivery to skin and nails is an area of great interest. The aim of this project was to develop lipidic and polymeric vesicles as drug carriers for the topical treatment of onychomycosis and cutaneous leishmaniasis. Drug-free and drug-loaded vesicles (transfersomes and polymersomes) were prepared and characterised for size, deformability, encapsulation efficiency, drug release, permeation into and through nail and skin and antifungal and anti-leishmanial activities. Relationship between vesicle deformability and their ability to deliver drugs to nails and skin was explored. Transfersomes and PMPC-PDPA polymersomes showed higher deformability compared to liposomes and PEGMA-MCH polymersomes, and were further tested. Terbinafineloaded transfersomes and polymersomes showed drug encapsulation efficiencies of 100% and 65% respectively, and very different drug release profiles, with transfersomes showing slow and incomplete release, while the pH-responsive polymersomes showed fast drug release at the appropriate pH. Fluorescent vesicles were found to be able to partially penetrate the nail plate, with transfersomes permeating to a deeper extent than polymersomes. Drug encapsulation in the vesicles increased its anti fungal potency against C. albicans and T. rubrum. Interestingly, drug-free polymersomes showed intrinsic antifungal activity against dermatophytes. Polymersomes were also investigated for their potential in the topical treatment of cutaneous leishmaniasis. Topically-applied polymersomes permeated into both healthy and infected mouse skin, with greater permeation through the infected skin. Amphotericin B-loaded polymersomes had encapsulation efficiencies of 20% and were significantly more active against Leishmania major and Leishmania mexicana in in vitro experiments compared to miltefosine, the only oral treatment for cutaneous leishmaniasis. It was shown that the deformable transfersomes and polymersomes can be used to encapsulate antifungal and anti-leishmanial drugs, can permeate into the skin and the nailplate, and have anti-fungal and anti leishmanial activities. Thus, their application in the topical treatment of skin and nail infections is promising.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available