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HIV continues to be a global healthcare challenge, with estimates suggesting there are currently 35.5 million infected people globally. To date, there have been an estimated 36 million HIV/AIDS related deaths worldwide. The story is changing however, with the advent of Highly Active Antiretroviral Therapies (HAART), allowing patients to live to normal life expectancies and with increasingly better quality of life. This, coupled with the fact that there has been a 40-fold increase in the number of people with access to antiretroviral therapy, has led to a 29% reduction in AIDS related deaths since 2005. Despite this encouraging data, there are still numerous limitations of antiviral therapy, including poor bioavailability, poor patient adherence, and emerging resistance. It is hoped that nanomedicine may offer a route to alleviating some of these issues by achieving an equal therapeutic concentration of drug but with a lower dose. The aims of this thesis were to develop a novel nanoemulsion based formulation of EFV and LPV and to assess the suitability of this formulation as dosage form. Nanoemulsions can be stabilised by surfactants, but often this can have unwanted safety profiles. Stabilisation can also be achieved using amphiphillic polymers that can be synthesised using biocompatible monomers like ethylene glycol. Chapter 2 demonstrates the synthesis of Ethylene Glycol based polymers using both conventional free radical and Atom Transfer Radical Polymerisation techniques. Nanoemulsions have previously been shown in the literature to increase the bioavailability of poorly water-soluble drugs, Chapter 3 shows the development and optimisation of an Oil-in-Water nanoemulsions. The data showed that nanoemulsions synthesised with volatile cosolvents were able to achieve sub 300 nm diameters and have good long-term stability. Increasing the accumulation and permeation of a poorly water-soluble compound should lead to improvements in bioavailability. Chapter 4 shows that the optimal nanoemulsion had comparable accumulation to aqueous solutions and superior apparent permeability cross Caco-2 cell monolayers. The antiviral activity was equipotent to the aqueous solution, as shown in Chapter 5. This confirms that nanoemulsion did not prevent the API from reaching its sight of action. Finally, all new formulations have the potential for detrimental side effects and immunological responses. It is therefore necessary to conduct pre clinical studies to predict such occurrences. Chapter 6 details the lack of immunological response seen in nanoemulsions, but highlights potential interactions with coagulation. In conclusion, this study has found that polymer stabilised oil-in-water nanoemulsions based on Castor oil have promising safety and pharmacological profiles. Further in vivo and studies are now warranted in order to further predict the suitability of nanoemulsions in man.

The history of the madrigal in England is a significant one, traversing the final decades of the 16th century to the present day; as a vehicle for music, the madrigal has been an inspiration to composers and singers alike. This thesis surveys the revival of interest in the madrigal from the early 18th century to the mid-19th century; it investigates the madrigal's resurrection through a seminal period of English musical history, and examines its rise in artistic and social contexts where nexuses are established with the Gothic Revival and the re-accommodation, from the late-18th century onwards, of Roman Catholicism in England. The examination of contemporaneous newspapers, musical journals, minute books and other operational apparatus that relate to both metropolitan and provincial madrigal societies has not only revealed how extensive are the existing archives, but has also allowed in-depth investigation and discussion of their meaning and impact. A core group of five antiquarians is also examined: Sir John Leman Rogers (1780-1847), William Hawes (1785-1846), Edward Taylor (1784-1863), Thomas Oliphant (1799-1873), and James Turle(1802-1882). These men were brought together by their fascination for old music under the aegis of the Madrigal Society (whose continuous existence of over 270 years makes it the oldest music-performing society today); they saw themselves as restorers of a long-lost national heritage, and as advocates of a return to excellence in musical composition. The composer Robert Lucas Pearsall (1795-1856), the most prolific of madrigal writers in the 19th-century, was caught up in the tide of the five men's work; the outcome was his production of some of the most exquisite vocal writing of his century. All six of these men are discussed in detail within the thesis. The end of this thesis gathers together the evidence examined, and arrives at the conclusion that despite the consistently small circle of amateurs and connoisseurs for whom madrigal singing was an interest and pastime in the 18th and early 19th centuries, their efforts nurtured and sustained the madrigal, and promoted it as a patriotic emblem of musical achievement. In so doing, they laid the foundation for a second wave of interest that rose again in the early 20th century, and established firmly the madrigal as a constituent part of English musical ipseity.