Supplying safe, appropriate and effective non-prescription medicines for customers in community pharmacies is a key role of pharmacists and pharmacy assistants in every country. However, in low and middle-income countries, including Vietnam, the quality of professional services from pharmacies is limited, unclear and has often been questioned. There is limited research about the real situation surrounding non-prescription medicine supply in community pharmacies in Vietnam. The factors that influence the supply of non-prescription medicines to customers and to what extent the service provision could be improved for the benefit of pharmacy customers needs to be explored. This study aimed to investigate non-prescription medicines supply in community pharmacies in Hanoi, Vietnam in order to provide scientific evidence about the situation. A mixed method approach was used in this study to provide valuable insights into what occurs during pharmacy staff-customer transactions. Following ethical approval, fieldwork observations were undertaken in five community pharmacies over a five week period from March to May 2011, this was followed by 22 semi-structured interviews with eight pharmacists and 14 pharmacy assistants who had been observed. The interviews enabled participants to express their perceptions and experiences regarding the supply of non-prescription medicines to customers in community pharmacies. Survey research, using a structured questionnaire, was conducted with 505 pharmacy customers who were asked to evaluate the pharmacy service that they had just received. Results from the three sources were triangulated and validated by comparing, contrasting, complementing and confirming in order to provide a better understanding of non-prescription medicines supply and make recommendations for improving the service provision in community pharmacies in Vietnam. The findings from this study indicate that factors influencing the supply of non-prescription medicines in community pharmacies include attitudes of pharmacy staff, their medical and pharmaceutical knowledge and their communication skills. The influence of the pharmacy settings, customer factors such as customers’ complex and diverse demands, the irrational use of medicines, using medicines following the suggestions of others, and tough customers were all factors that impacted on staff-customer transactions. Being conveniently located, the pharmacy offering reasonably priced medicines and being a large pharmacy with a good reputation were also considered important impacting on customer selection of community pharmacy. The results of this research show that there are limitations in pharmacy service provision and there is a discrepancy between pharmacy staff perceptions and actual practice in terms of attitudes. Poor performance, in many situations, did not come from a lack of knowledge; rather it appeared to result from the negative attitudes of pharmacy staff. Such negative attitudes of pharmacy staff are likely to be related to their focus on just short-term profit rather than focusing on a balance between short-term and long-term benefits for both customers and pharmacies. Positive attitudes, taking greater responsibility, customer loyalty and long-term benefits were ignored. Poor performance of pharmacy staff, to some extent, was also affected by their education and training. Some educational organisations have commercialised their training activities and paid too much attention to the quantity of graduated students rather than the quality of their education and training. This study has important implications for the improvement of the responsible supply of non-prescription medicines in community pharmacies in Vietnam including the identified needs for attitude interventions and training. New subjects should be added to the pharmacy students’ curricula and training should be developed for pharmacy assistants in areas such as communication skills, customer psychology, selling skills and patient safety. For pharmacists and pharmacy assistants, gaining treatment experience from customers’ feedback and keeping up to date with new information should be a continuous activity. Close co-operation between health authorities, policy makers and researchers needs to be developed in conducting further research and implementing appropriate policies, in order to improve the service provision in community pharmacies in Vietnam.

The formation of three-dimensional (3D) models for tissue engineering purpose provides a more conducive environment to enable complex biological interactions and processes between cells, biomaterials and bioactive molecules. Microparticles (MP) can be used as supporting matrix for 3D construct in cells and a carrier to deliver bioactive agents for cell development and differentiation, particularly for bone tissue engineering. Poly(glycerol adipate) (PGA) is a potential polymer for tissue engineering purposes as it is biodegradable and has biocompatibility with several cells. The aim of this study is to modify PGA polymer for MP with well-defined properties for drug encapsulation and release, promote cell-MP interaction and evaluate the osteogenic differentiation with MP incorporation in mouse embryonic stem (mES) and osteoblast cells. The PGA polymer has been modified by substituting 40% pendant hydroxyl groups onto the polymer backbone with stearoyl (C18) groups to increase encapsulation efficiency of drug within MP. Further modification was tethering one carboxyl terminus in PGA polymer with maleimide-poly(ethylene glycol) (MIHA-PEG-NH2) linker for ligand attachment on the surface of MP. Collagen, as a ligand, was modified by attaching iminothiolane to give a functional thiol group for interaction with maleimide group on the surface of 40%C18-PGA-PEG-MIHA MP. The microparticles were prepared using an emulsification method. Dexamethasone phosphate (DXMP) and simvastatin (SIM) were encapsulated within the MP. The MP-cell aggregate formation was evaluated as well as cell metabolism activity. The effect of polymer modification on drug release from MP was evaluated in the cells by analyzing osteogenic differentiation in cells. The MP prepared from modified PGA polymer exhibited high encapsulation efficiency of SIM in MP. By adjusting the formulation parameters, the release of SIM from MP could be extended to 21 days. The collagen attachment on the surface of 40%C18-PGA-PEG-MIHA MP promoted cell metabolic activity and produced more extensive markers related to osteogenic differentiation.

Following the stability analysis, a testing protocol was devised and the legal and ethical obligations of the pharmacist in the addition of drugs to PN considered

In order to investigate further the mode of action of these compounds, synthesis of proteomic probes was attempted. Synthetic design and attempts are presented chapter VII. To establish whether there was 24-SMT present in the blood stream form of T. b. brucei, a Northern blot was carried out. This confirmed transcription of the enzyme which was then cloned, over expressed and purified (Chapter VIII). Enzyme assays were carried out against the recombinant enzyme.

Malaria continues to pose a significant global health and socio-economic burden on those regions where it is endemic. Despite substantial investment in the delivery of artemisinin-based combination therapies, causing a fall in malaria mortality, recent data suggest that this parasitic disease still imposes a significant impact. A major problem is the narrow drug discovery pipeline, made worse by reports of artemisinin resistance. In recent years, high-throughput screening of natural products derived from plants and marine organisms has led to the discovery of potent anti-malarial indole alkaloids (such as dihydrousambarensine), many of which contain an indoloisoquinoline core. Building on previously discovered methodology in our group, we have developed a series of novel, enantiomerically pure, synthetic indoloisoquinoline and their potential as anti-malarial leads was assessed. The structure-activity relationship of these compounds was investigated in several areas and a lead compound was generated with an activity close to that of a known anti-malarial natural product dihydrousambarensine.

Folate uses the natural endocytosis pathway via the folate receptor (FR) to enter the cells. Folate conjugation to small or macromolecular therapeutics has hence been exploited for intracellular delivery to, particularly, cancerous cells. This work reports on the expression and functionality of FR in polarised cell monolayer models of respiratory and gastrointestinal mucosa with the view to assess its potential for delivery of folate-modified macromolecular therapeutics either intracellularly or across the epithelium. Four cell lines representing bronchial and intestinal epithelium; cancer-derived intestinal Caco-2 and bronchial cell line Calu-3, and noncancerous intestinal and bronchial cell lines IEC-6 and HBEC were cultured on permeable membranes to produce polarised monolayers. Expression of FR was confirmed by RT-PCR and Western blot analysis for all the tested cell types and shown to be dependent on culturing time. The functionality of the receptor for endocytosis was demonstrated by a model macromolecular folate conjugate (fluorescent ovalbumin-folate (OVA-FA)), whereby significantly higher cellular uptake of the folate-conjugate, relative to non-folate control, was clearly demonstrated. Importantly the data showed that the expressed folate receptor was capable of mediating transport of the macromolecular folate conjugate across (transcytosis) the cells in the polarised monolayers. Preliminary studies led to investigation of the folate mediated uptake and transport of folate modified nanoparticles (NPs). It was shown that folate modified NPs traversed the Calu-3 layers and studies characterizing this transport indicated folate involvement in this process. Adsorption of OVA-FA on the surface of NPs was seen to promote their cellular uptake and transport across the cell layers. To examine the mechanism of cellular uptake and transport of folate modified nanoparticles, various endocytic inhibitors were employed. The study demonstrated an involvement of the caveolar pathway in internalization of folate modified nanoparticles; as judged from a significant reduction of internalization in filipin (inhibitor of caveolar pathway) treated cells. Moreover, the work also showed evidence of transport of folate-modified nanoparticles via the caveolar pathway, since translocation of nanoparticles across the cell monolayer was absent when this path was inhibited. Disruption of actin filament and microtubules caused no difference in cellular uptake of NPs but increased the transcytosis of folate modified NPs. Confocal microscopy, Transmission Electron Microscopy (TEM), Total Internal Reflection Microscopy (TIRM) and Total Internal Reflection Florescence microscopy (TIRFM) were used to confirm and visualize quantitative data. This study also investigated the effects of surface ligand distribution pattern (ligand clustering and density) on the internalization of nanoparticles by Calu-3 cells cultured as polarised layers. The density of the displayed ligand was manipulated by controlling the conjugation level of folate-ovalbumin, while ligand clustering was achieved by co-adsorption of varying mixtures of folate-ovalbumin conjugate (at different ligand density levels) and unconjugated ovalbumin. Increasing ligand density on the nanoparticle surface resulted in increased internalization of modified nanoparticles by the cells, up to a saturation level. Surface ligand density also affected the cellular uptake pathway; from predominantly clathrin to predominantly caveolae-mediated as the ligand density was increased. It was further demonstrated that surface clustering of the folate ligand enhanced cellular internalization of nanoparticles, relative to its dispersed surface distribution.

The tropical rainforest of Malaysia is considered as one of the most evolved and complex ecosystems in the world that serves a vast untapped biodiversity of natural resources. Exploitation of medicinal plants for bioactive compounds is of great potential and could be an imperative source of providing new vistas for novel drug discovery and development. The study was undertaken to evaluate the in vitro pharmacological properties of Artabotrys crassifolius including antibacterial, antifungal, anticancer and antioxidant activities of the plant. The leaves and bark of Artabotrys crassifolius were extracted sequentially using hexane, chloroform and ethanol. The prepared crude extracts were subjected to phytochemical screenings for the presence of alkaloids, cardiac glycosides, flavonoids, phenolic compounds, saponins, tannins and terpenoids. Kirby-Bauer disc diffusion assay was conducted to examine the antibacterial and antifungal activities of crude extracts against ATCC and clinical strains. The anticancer effect of crude extracts was investigated against human breast and colorectal carcinoma cell lines using MTT assay whereas the antioxidant potential of crude extracts was assessed using TPC, TFC, ABTS, DPPH and FRAP assays. Among the crude extracts studied, hexane and chloroform extracts of bark exhibited pronounced antibacterial activities against ATCC and clinical strains with zones of inhibition ranging from 8.23±0.25 mm to 13.70±0.26 mm and 7.75±0.25 mm to 13.68±0.28 mm respectively. However, all the crude extracts were found to be devoid of antifungal activity except for hexane extract of bark which was able to inhibit the growth of the tested Candida species with zones of inhibition ranging from 7.81±0.27 mm to 9.77±0.25 mm. In addition, chloroform extract of bark was highly active against all of the tested carcinoma cell lines with GI50 values ranging from 4.23 µg/mL to 9.45 µg/mL, while hexane extract of bark potently inhibited the growth of MDA-468 breast and HCT-116 colorectal carcinoma cell lines with respective GI50 values of 6.10 µg/mL and 16.45 µg/mL. Furthermore, ethanol extract of bark that possessed the highest total phenolic and flavonoid contents (268.29±12.36 mg GAE/g and 179.54±4.98 mg CE/g) was shown to demonstrate prominent scavenging activities against ABTS cation and DPPH radicals with IC50 values of 16.50 µg/mL and 16.54 µg/mL respectively, as well as exceptionally high antioxidant power with FRAP value of 1884.35±83.78 µmol Fe(II)/g. The chromatographic separation of chloroform extract of bark led to the isolation of four alkaloids, namely artabotrine, liridine, atherospermidine and lysicamine. Among the compounds isolated, artabotrine displayed high antibacterial properties with respective MIC and MBC values ranging from 1.25 µg/mL to 5 µg/mL and 1.25 µg/mL to 20 µg/mL against all of the tested ATCC and clinical bacterial strains, with the exception of Actinobacillus sp. and Klebsiella sp. Moreover, artabotrine was highly active in HCT-116 colorectal and MCF-7 breast carcinoma cell lines with GI50 values of 3.34 μM and 3.49 μM respectively. In conclusion, exploration of the in vitro pharmacological properties of Artabotrys crassifolius revealed that artabotrine with dual antibacterial and anticancer activities may represent a new generation of potential drug candidates for the treatment of bacterial infections and cancer. Hence, further in vivo studies and clinical trials are required to ascertain the efficacy, safety and mechanisms of action of artabotrine prior to application in the pharmaceutical industry as natural therapeutic agents.

Pharmacy as a profession is changing rapidly in the UK. Over recent years, the increased utilization of ready-prepared drugs has led to a decline in the need for the traditional skills of formulation, while computerization has resulted in a situation where much of the routine dispensing work can be undertaken by less qualified personnel. The decline in the traditional aspects of pharmacy has been matched by the emergence of a much greater advisory role. Pharmacy practice researchers have been drawn to support these developments by investigating related areas, but the common factor linking this research is its focus on clinical as opposed to communication issues. Rather than investigating the nature of face-to-face interaction between pharmacists and clients as a topic in itself, researchers instead have been largely concerned with patient/health care system mteractions as a function of drug therapy. Those few studies that have focused exclusively on communication have done so from a quantitative, social psychology framework, thus ignoring the two way, reactive nature of the interaction process. This study, using data collected from patients' and carers' consultations with pharmacists in a hospital paediatric oncology outpatient clinic, uses the sociological methodology of Conversation Analysis (CA) in order to analyze the encounters which take place. In so doing, it aims to shed some light upon what is actually involved in the process of "patient counselling" in this setting. The body of CA literature which considers advice-giving in health care settings provides the starting point for a consideration of the ways in which pharmacists give advice in this setting, and how this is responded to. The aims are thus twofold: to enlarge the methodological resources of PPR, and also to begin an examination of the communicative competencies required of pharmacists in this setting. NB. This ethesis has been created by scanning the typescript original and may contain inaccuracies. In case of difficulty, please refer to the original text.

The cannabinoid receptors CB1 and CB2, which belong to the rhodopsin family of GPCRs, are implicated in the pathology of various disease states. As drugs targeting these receptors remain limited, novel cannabinoid receptor ligands represent an unmet need with substantial therapeutic potential. We present here the construction and application of homology models of the human CB1 and CB2 cannabinoid receptors based on the crystal structure of the human adenosine A2A receptor for the structure-based design of novel ligands based on the fenofibrate scaffold. Models were refined through molecular dynamic simulations in a lipid bilayer, and were validated via the prediction of known ligand binding affinities, enrichment studies and assessment of predicted ligand binding modes. These validated models were subsequently used in predicting the binding mode of fenofibrate derivatives to the cannabinoid receptors. The predicted binding mode of these fenofibrate derivatives to the CB2 receptor showed good agreement with known mutagenesis data, indicating the binding of these compounds to be stabilized primarily by hydrogen bonds with W5.43 and C7.42, aromatic stacking with F2.57, F3.36 and W6.48, and hydrophobic contact with F2.64, V3.32 and I5.47. A series of novel ligands was derived based on these findings, docked into our model, synthesized and pharmacologically evaluated at the CB2 receptor. The pharmacology of these ligands validated our modelling predictions and binding mode hypothesis, with several of these ligands showing unique pharmacology by binding in an allosteric manner. These findings may be used to guide the design of further derivatives and highlight the promise of the fenofibrate scaffold in the development of novel CB2 receptor ligands.

Media promotion of the ideal body as slimness for women and muscularity for men, has led to increasing numbers of both genders reporting dissatisfaction with their bodies and trying to change using weight control products. It has been suggested that pharmacists can play a key role in promoting healthy lifestyles and weight management. The main aim of the research study was to examine the impact of media on body image perception and to investigate the role of pharmacists in weight management. This thesis consists of three studies: an evaluation of weight control websites, a body image survey of young adults and interviews with pharmacists. The results from the evaluation study showed that the quality of most weight loss (64%) and weight gain product advertisements (80%) was generally poor, principally due to the use of misleading claims and a lack of useful information. These data complement the survey that university students reported rarely being influenced by weight control product adverts and hardly considered using these products as a method for changing weight. The survey also showed that most participants of both genders (71%) felt satisfied with their body image. However, the findings in this study indicated that there was a relationship between a high level of body image concern and self-perception of being overweight and the attempt to lose weight. Interviews with pharmacists showed that they were unlikely to be actively involved in reducing obesity problems and promoting healthy lifestyles in the community. Although the prevalence of body dissatisfaction and the use of weight control products among these young adults may not be as high as has been reported elsewhere, healthcare professionals, including pharmacists, need to be aware of this problem when providing advice or consultations for young adults. Healthcare professionals should promote the benefits of healthy lifestyles as well as providing information about potential problems of harmful weight control strategies. The effect of ethnicity and culture on body image concern warrants further. The availability of weight control products and quality of information provided should also be further examined.