Fatimah; (2023) Electrospinning of Stimuli-Responsive Nanofibers for Advanced Drug Delivery. Doctoral thesis (Ph.D), UCL (University College London).

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Text Fatimah 14098094 - Dept. Pharmaceutics - PhD thesis report.pdf - Accepted Version Download (32MB) | Preview

Abstract

The research in this thesis aims to develop novel cancer treatments via smart polymeric drug delivery systems. This was achieved by developing advanced polymeric fibres which are responsive to pH- and/or temperature stimuli. The fibres were produced utilising various electrospinning techniques including single-needle electrospinning (to produce monolithic fibres) and coaxial electrospinning (to produce core-shell fibres). Chapter 1 provides a brief introduction of cancer, its pathology and current treatments, and challenges in its therapy. Next, a brief discussion on the drug delivery systems available on the market and being researched is presented, including the development of polymeric smart materials for controlled drug delivery and the use of the electrospinning technique in fibre fabrication. Current scientific gaps are indicated and the overall rationale and aims of this thesis are outlined. Chapter 2 describes the materials and general methods used in experimental work. Chapter 3 describes the fabrication of core-shell nanofibres for controlled delivery of the anticancer 5-fluorouracil or ferulic acid. These were encapsulated in cyclodextrins and combined with the diagnostic agent diethylenetriaminepentaacetic acid gadolinium (III) hydrate (GdDTPA) to prepare theranostic formulations. This was achieved using the coaxial electrospinning method, with poly(ethylene oxide used to construct the core and Eudragit S100 as the shell. The aim of this formulation was to provide targeted delivery of the drug and diagnostic agent to the colon, but in vitro experiments indicated that this approach was not viable as there was significant release in low-pH conditions representative of the stomach. 5 Chapter 4 focuses on the synthesis of a smart polymer utilising OEGMA300 (Oligo(ethylene glycol) methyl ether methacrylate, Mw 300 g/mol) and DiEGMA (Di(ethylene glycol) methyl ether methacrylate) monomers. These were used to construct a lower critical solution temperature (LCST) polymer, and the process was optimised to obtain a system with an LCST of 40 ºC, slightly above the physiological temperature and within hyperthermia range. This polymer was then electrospun with polycaprolactone (PCL) to fabricate fibre mesh. A faster drug release occurred when the temperature was set below the LCST due to the hydrophilicity of P(OEGMA300 -co-DiEGMA) polymer hence increasing solubility. Upon increasing the temperature above LCST, the drug release was slower, however a higher cytotoxicity effect on Caco2 cell lines was observed due to synergic effect between the released drug and induced hyperthermia. Chapter 5 presents a further advanced drug delivery system comprising the optimum thermoresponsive polymer from Chapter 4 and Eudragit S100. These were blended and electrospun to fabricate a dual pH- and thermoresponsive fibres mesh. This dual pH-thermoresponsive nanofibres had slow release characteristics below the critical pH and above LCST, and gradually increase upon a rise in pH and lower temperature. Cytotoxic study showed that induced hyperthermia resulted in higher toxicity against Caco2 cell lines. Chapter 6 summarises the results from all experimental work performed in this thesis and makes suggestions for possible future work.

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