It has been widely reported that cell culture dimension and microenvironment influence cell proliferation, differentiation, and gene expression, which lead to different interactions between drug delivery systems and cells. The development in evaluation of drug delivery systems has reached the stage where investigations are now concentrating on intracellular uptake and subcellular localization of drug delivery systems.This thesis investigates the use of three-dimensional (3-D) tissue culture models to study how nanoparticles (NPs) may behave in vivo. Poly (glycerol-adipate) (PGA) NPs can degrade into glycerol and adipate, which are not having toxic and anyundesirable local or systemic effects in the host. Following on the initial physicochemical characterization of PGA NPs loaded with drug and fluorescent dyes, investigations moved on to the biological studies of NPs in various cell culture model, e.g. monolayer culture, 3-D culture models, and brain tumour invasion model. Particle size, surface charge, and hydrophobicity are important features affecting the amount of particles taken up by cells and intracellular localisation of particles. Thus, the physicochemical properties of drug and fluorescent dye loaded PGA NPs were assessed by Photon Correlation Spectroscopy, Laser Doppler Anemometry, and drug/fluorescent dye loading studies. These studies indicated that physicochemical properties of drug, fluorescent dyes and PGA polymer could influence drug /fluorescent dye loading, which results in different particle size and surface charge of PGA NPs. Quantitative and qualitative investigations into the influence of cell culture dimension on uptake of NPs by cells, both by confocal fluorescence microscopy and flow cytometry, revealed that DAOY cells took up NPs more effectively when in 3-D spherical aggregate culture than in 2-D monolayer culture while uptake of NPs by normal brain cells was lower in 3-D cell culture than that seen in 2-D monolayer culture. This resulted in intracellular fluorescence intensity about 6 times higher in DAOY aggregates than normal brain cell aggregates while in monolayer culture mixed brain cells took up 2 times as many NP as the DAOY cells. The results from studies of NPs migrating through aggregates and tissue slices also indicated that penetration ofNPs in 3-D culture models was affected by the structure of the interstitial compartment and composition of extracellular matrix. Microscopic investigation of the histology of a co-culture invasion model of DAOY aggregates and a organotypic brain slice confirmed that DAOY cells massively invaded into cerebellum slices after a 4-day co-culture while the invasion of DAOY cells were limited within cerebral cortex slices even after a 6-day co-culture. Selective uptake of NPs by host cells and brain tumour cells were also assessed in this 3-D brain tumour invasion model. It showed that most NPs were taken up by DAOY cells instead of brain cells.

Aims of study The overall aim of this study was to investigate factors affecting service delivery within a national pharmacy chain, from the perspective of pharmacists and consumers, using asthma services as an example. Data were collected to explore the current environment and opportunities available to pharmacy, the factors affecting service delivery, and to identify recommendations for future service models. The impact of the design and route of service implementation were studied through two different types of asthma services. Methods The brief intervention in asthma was designed centrally and implemented nationally, whilst the asthma service was designed and implemented locally by a group of pharmacists. A triangulation of qualitative and quantitative methods were used throughout this study, including an omnibus survey, audits, mystery customer research, customer and pharmacist interviews, and a review of the dispensing data. Results A total of 81 facilitators, 45 barriers and 23 motivators were identified. In addition to extending those factors that had been previously recognised within the literature, new factors were also identified. Firstly, the route and design of service implementation to promote local ownership and responsibility for delivery of services was found to be a key factor, as was having flexibility in the length and content of service delivery. Clear and visible benefits to the pharmacists delivering the service, the customers accessing the service, and the pharmacy organisation were also found to play an important role in the delivery of services. Conclusions This is the first large scale study of its kind to look at all the factors involved from the perspective of both customers and pharmacists, and many of the facilitators and barriers identified extend beyond those provided within the current literature. The motivators identified within the previous studies have been from the perspective of pharmacists only. This study has looked at the perspective of not only pharmacists, but also the motivators to customers and the service provider. Based on all the factors identified throughout this study, a number of recommendations have been made for future service delivery.

Pullulan has been chemically modified by the incorporation of various hydrophobic molecules, to produce two types of derivatives (hydrophobically modified carboxymethyl pullulans (HMCMPs), and crosslinked carboxymethyl pullulan). The foregoing modifications were performed in two steps from the parent pullulan. The first step involved carboxylation of pullulan with sodium chloroacetate yielding carboxymethyl pullulan (CMP). The second step involved the medication of CMP by coupling different amine functionalized molecules onto the carboxylic groups of CMP, using the coupling agent dicyclohexylcarbodiimide. The amines used in this modification step were: hexadecylamine, decylamine, cadaverine (1-5 diaminopentane), and three jeffamine® (polyoxypropylenediamine) compounds of differing molecular weights (230, 400 and 2000). Results concluded that all six pullulan derivatives show an increase in reduced viscosity to varying degrees, compared to the parent pullulan. Characterization of pullulan and the derivatives concluded that the correct structures have been synthesised. Gel permeation chromatography confirmed that four pullulan derivatives had been crosslinked (due to doubled molecular weight terms), and a further two have increased in molecular weights, with no increase in polydispersity indices. Isothermal titration calorimetry experiments were initially performed on model systems (two different ß-cyclodextrins, and benzoic acid and eletriptan hydrobromide), and then on pullulan and the derivatives with eletriptan hydrobromide. These experiments probed the nature and extent of drug binding interactions. Results concluded that pullulan derivatives showed exothermic drug binding interactions with the named drug, with the exception of jeffamine 2000 crosslinked CMP, which exhibited endothermic interactions with the titrated drug. Pullulans excellent film forming capabilities may lead these polymers to a novel oral dosage form containing active (dissolving films).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1941. / Typescript. Includes abstract and vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Proefschrift--Rijksuniversiteit te Utrecht, 1932. / Includes bibliographical references (p. 74-77).

Doutor -- Escola Nacional de Saude Publica, Rio de Janeiro, 1999.

Doutor -- Escola Nacional de Saude Publica, Rio de Janeiro, 1999.

Doutor -- Escola Nacional de Saude Publica, Rio de Janeiro, 2002. / SAUDE PUBLICA.

Thesis (M. CM)--Hong Kong Baptist University, 2006. / Dissertation submitted to the School of Chinese Medicine. Includes bibliographical references (leaves 30-32).

Thesis (Ph.D.)(Botany)--University of Pretoria, 2006. / Includes summary. Includes bibliographical references. Available on the Internet via the World Wide Web.