Submitted in partial compliance with the requirements of the Master’s Degree in Technology: Homoeopathy, Department of Homepathy, Durban University of Technology, Durban, South Africa, 2015. / Introduction This study was a double-blind, placebo controlled proving of Panthera leo 30CH (claw of a African lioness); the aim being to determine the effect of this substance induces on healthy persons and in doing do explore the homoeopathic therapeutic potential thereof, in addition a subsequent comparison with the provings of Lac leoninum (milk of a lioness) (Sankaran,1998) (Herrick,1998) was performed. Objectives The primary objective of this proving was to determine the effect that Panthera leo 30 CH on healthy provers so that the therapeutic potential of the substance could be determined. The secondary objective was to compare the Materia medica of Panthera leo with that of Lac leoninum (Herrick, 1998) and Sankaran (1998). Lastly, the third objective was to further develop the homoeopathic Materia medica by adding the remedy picture of Panthera leo. Methodology The drug proving of Panthera leo was conducted as a randomized, exploratory, double blind placebo controlled study. Thirty participants (healthy volunteers) who met the inclusion criteria (Appendix B) participated in the proving, twenty – four were given the verum and the remaining six placebo. Upon obtaining written informed consent the researcher performed a full case history and comprehensive physical examination on each prover before commencement of the proving. A subsequent follow up case history and physical examination at the end of the proving was also performed to establish whether provers had returned to their respective healthy states. The provers took their first dose of the proving remedy at a dosage of 1 dose three times daily for 2 days and recorded all symptoms they experienced in their respective journals according to the guidelines in Appendix C. On completion of the proving, all provers handed in their journals which were then transcribed, assessed and analyzed. An extensive comparison between the proving of Panthera leo and the two provings of Lac leoninum (Herrick, 1998) (Sankaran, 1998) followed. The respective remedies were compared and contrasted with respect to Materia medica and repertory and similarities and differences highlighted. Results A total of 1255 rubrics were obtained of which the mind section of the Materia medica weighed heavily comprising 35 % (435 rubrics) of the proving symptoms, the generals section (11% = 135 rubrics) and head section (9% = 109 rubrics) respectively. Therefore it can be suggested that this remedy’s sphere of action is limited largely to the mind (emotional state) however unique physical indications specifically regarding headaches are also within its sphere of action. Of the total, 1255 rubrics that were obtained only 11% (138 rubrics) where shared with the two other provings of the African lion (Herrick 1998 & Sankaran 1998); as suggested by Naude (2011) one can speculate that these shared symptoms may represent the unique mammalian component of the animal the differences however considerably outweigh the similarities between these provings and for this reason one can conclude that factors in addition to the species of animal from which the remedy is sourced further influence the resultant proving symptoms. Conclusion It can be concluded that Panthera leo 30CH produced clearly observable symptoms in healthy provers who participated in this proving, furthermore there was clear congruency between certain aspects of this proving and that of Herrick and Sankaran however such similarities were limited.

Submitted in partial compliance with the requirements of the Master’s Degree in Technology: Homoeopathy, Department of Homeopathy, Durban University of Technology, Durban, South Africa, 2015. / INTRODUCTION A homoeopathic drug proving was conducted by Master’s students at the Durban University of Technology (DUT). The proving substance was nail shavings obtained from an African lioness (Panthera leo). The primary objective of this study was to identify the symptoms produced by healthy individuals in response to Panthera leo 30CH; this was done by administering the proving remedy (Panthera leo 30CH) to healthy individuals, who recorded the symptoms they experienced after taking the remedy. The secondary objective was to compare the symptoms produced to the ethology of the African lion. The final objective was to further develop the materia medica by adding the remedy picture of Panthera leo. METHODOLOGY This study was qualitative and exploratory in nature. The study took the form of a randomised, double-blind and placebo controlled trial. A total of 30 provers, who met the inclusion criteria (Appendix C), participated in this study. The provers were randomly assigned to either a verum or placebo group, such that 24 received verum (Panthera leo) and 6 received placebo. Neither provers nor researchers had knowledge of which provers were in each group until the study was complete, and provers did not have any knowledge regarding the nature of the proving substance. Before commencing the study all provers signed relevant information and consent documents. The researcher then took a full case history and performed a physical examination. Provers recorded their baseline state for 7 days in a journal, prior to taking the verum or placebo, as administered to them. After recording their baseline state for 7 days, they took their remedies and continued to record their symptoms for a minimum of 2 weeks, or until the proving symptoms ceased. Once they had completed recording in their journals, a post-proving case history was taken and a physical examination was performed. All journals were collected and analysed by the researcher. The remedy was manufactured by triturating the crude substance up to the 3rd centesimal potency. This was then converted to a liquid potency and further diluted up to the 30th centesimal potency. Neutral granules were impregnated with Panthera leo 30CH, and dispensed as 10 granules in 500mg of lactose powder. The placebo was dispensed as 10 granules, which were impregnated with 96% ethanol, in 500mg lactose powder. Each prover received 6 lactose powders, containing either verum or placebo. The manufacture of Panthera leo was done according to the methods and guidelines stipulated in the German Homoeopathic Pharmacopoeia (Benyunes, 2005) RESULTS The proving of Panthera leo 30CH produced a total of 1234 rubrics, which represent a wide variety of mental, emotional and physical symptoms. The main themes that emerged from the mental and emotional symptoms included anger, aggression, irritability, poor concentration and fear. Physical symptoms included catarrh, constipation, diarrhoea, diminished appetite, fatigue, insomnia, thirstiness and headaches. A comparison was made between the symptomatology of Panthera leo and the ethology of the lion. Some of the themes of symptoms which corresponded with the ethology of the lion included ‘anger’, ‘audacity’, ‘ennui’, ‘increased appetite and thirst’, ‘responsibilities’ and ‘children’. CONCLUSION The objectives of this study were fulfilled, as the proving of Panthera leo produced a wide variety of clearly identifiable and observable symptoms amongst the healthy individuals recruited. There was a remarkable correlation of a portion of the materia medica with the ethological features of the African lion. As a result of this study, the materia medica of Panthera leo was well outlined and will be added to the existing body of homoeopathic materia medica for application and utilization in clinical practice

Submitted in partial compliance with the requirements of the Master’s Degree in Technology: Homoeopathy, Department of Homeopathy, Durban University of Technology, Durban, South Africa, 2015. / Homoeopathy has advanced as an empirical art and has become a modern age science backed by the kind of massive research data and critical reviews that helps scientific knowledge become acceptable within the global knowledge space. Two centuries ago, the practice of homoeopathy was possible with a few hundred proven remedies of that time but as this science developed through both research and collection of empirical data the number of remedies available increased exponentially. As both the study of remedies and the remedy selection process became more challenging, group analysis by famous homoeopaths such as Farrington (1992), Sankaran (2003), Scholten (1993), Mangliavori (in Vidal 2005) emerged. Currently, with a database of over 3000 remedies available for prescription, group analysis, though a contested approach has proven to be an adequate tool that helps consolidate mass homoeopathic data into meaningful groupings that makes both the study of remedies and their application in practice easier. Classifying homoeopathic remedies into groups by means of group analysis and allowing such methods and results thereof to go through rigorous critiquing refines homoeopathic knowledge and improves its ability to sustain itself as a competent science. Homoeopathy has emerged as a technologically inclined science, utilising various software programs enabling more thorough correlation of symptoms and remedies and so improving the prescription process. Software programs have proven to be very useful tools for the development of group analysis. The aim of this study was to extract the common characteristic symptomatology of five selected homoeopathic remedies belonging to the acidum family as represented in the known materia medica and repertory. The acidum remedies appearing in Radar® 10 repertory (Archibel 2008) were analysed in terms of rubric representation (frequency) and the top five were selected for inclusion in the study. The top five remedies were: Nitricum acidum, Phosphoricum acidum, Muriatic acidum, Sulphuricum acidum and Fluoricum acidum. All rubrics in which the selected remedies appeared were extracted using the homoeopathic software package Radar® 10 (Archibel, 2008) and analysed for sensations and active, passive and compensation reactions of the selected remedies, as per Sankaran (2002). The common primary sensations identified were, burning, sore, swelling, pressing, cramping, dryness, weakness, tearing, and coldness. There were also sensations of anxiety, restlessness, delirium, delusions, dullness, sadness and cheerfulness. Active reactions identified were: hot, heat, inflammation and sensitivity. Passive reactions identified were: coldness, numbness and weakness. Compensation reactions identified were: restlessness, hurriedness, intense reaction and passion. Miasmatic keywords as per Sankaran (2002) were used to determine the miasmatic tendencies of the selected top five acidum remedies. In general all acidum remedies appeared to have a dominant syphilitic miasmatic tendency but acidums were present through all the miasms. Their miasmatic tendencies are easily recognised when viewed in the light of their pathophysiological processes. The pathological tendencies of acidum remedies examined in this study include: haemorrhoids, general haemorrhage, syphilis, warts, neoplastic and non-plastic tumours, irritable bowel syndrome (reflux, colic, constipation), rheumatism, muco-cutaneous ulcerations (STIs, Xerostomia, diabetic ulcers) and bone diseases (osteoporosis, osteitis, and peri-osteitis). The results of this research were compared to the findings of Scholten (1993) and Mangialavori and Marotta (2005). It is the researcher’s view that Sankaran’s methodology of group analysis which he used to explore biological groups of remedies (plants and animals) is adequate for use with non-biological groups of remedies such as mineral acidums. The researcher found group analysis methodology worthy as a tool for classifying the mass data of acidum remedies into orderly sets of meaningful data. Group analysis is consistent with the laws and principles of homoeopathy and encourages the use of materia medica and repertory which are fundamental to the study and application of homoeopathic knowledge. / M

Submitted in partial compliance with the requirements of the Master’s Degree in Technology: Homoeopathy, Durban University of Technology, Durban, South Africa, 2016. / There are now several thousand remedies available to a homoeopath and this number is continually increasing with the increase in homoeopathic research and provings. This growing wealth of data does, however, make choosing a homoeopathic remedy difficult and some homoeopaths argue that the essence of homoeopathic remedies are being lost in this excess of data. In an attempt to more accurately see a remedy’s ‘picture’ and gain deeper insight into remedies, Scholten (1993), Sankaran (2005a) and Mangialavori (2010) developed different methods which can now be collectively referred to as “group analysis”. The aim of group analysis is to find symptoms, sensations and pathological tendencies that are common to all remedies within a group. This study involved applying Sankaran’s group analysis approach to the psychoactive plant drug remedies with the rationale of filtering and organizing the mass of data we now have available on this group. This will enable both students and professionals of homoeopathy to develop a deeper understanding, and hence greater utilization, of the psychoactive plant drug remedies. The following five homoeopathic remedies were chosen for this study on the grounds that they have all been extensively proved through both homoeopathic provings and cured clinical cases and there is a vast amount of literature available on these remedies in materia medica and repertories: • Anhalonium lewinii (Cactaceae family) • Cannabis indica (Hamamalidae family) • Coffea cruda (Rubiaceae family) • Nux moschata (Magnolianae family) • Opium (Papaveraceae family) A computer repertory search was conducted using RadarOpus (Archibel, 2014) to extract all rubrics containing the selected remedies. Parameters were set to retain only rubrics that have less than 50 remedies and at least two of the selected psychoactive plant remedies in them. This was to ensure that only well-defined, characteristic remedies were looked at. The rubrics were visually analyzed, compared and contrasted to determine the common sensations within them and mental, general and particular symptoms were analyzed in terms of Sankaran’s model of Vital Sensation (2005a). The vital sensation of the psychoactive plant drug remedies was found to be that of horror, fear or fright. All the remedies belonging to this group experience the sensation of horror either through their perception of pain or through dreams, visions, hallucinations or anxiety. This sensation pervades all these remedies which are constantly trying to escape this sensation by either increasing or decreasing their activity and sensitivity. The active reaction to the sensation of horror is to increase activity. This is expressed through increased sensitivity; mental clarity; sensations of contraction, fullness, heaviness, heat or moisture; delirium, hallucinations and instability. The passive reaction to the sensation of horror is to decrease activity. This is expressed through insensitivity; lack of mental clarity; sensations of expansion, emptiness, lightness, cold or dryness; sleep, stupor and unconsciousness. The compensation, or coping mechanism that psychoactive plant drug remedies develop, is a transcendence of their condition: they transcend, or escape, their condition by no longer feeling or doing anything, by becoming numb and insensitive. The researcher suggests that although the remedies of the psychoactive plant drug group can be classified according to different miasms, the over-riding miasm of this group is the sycotic miasm with its fundamental sense of having a ‘fixed weakness’ within themselves. The researcher also proposes that the psychoactive plant remedies have an affinity for the central nervous system and for ailments caused by strong emotions such as joy, anger, excitement, fear or fright. These remedies tend to produce pathologies of the central nervous system and sleep including increased reflexes, involuntary motions, trembling, jerking; weakness, atrophy, slowness, paralysis; unconsciousness; catalepsy; Autism Spectrum Disorders; hypersensitivity; insensitivity or absence of sensitivity; pain; formication; mental confusion, poor comprehension, nonsensical speech; memory disorders; delirium, hallucinations, schizophrenia; mood disorders; behavioural disorders; anxiety; insomnia, narcolepsy and nightmares. The researcher found group analysis to be a powerful methodology that, if employed correctly, can aid homoeopaths to learn and understand remedies in their ‘totality’. / M

國際市場對植物藥和中藥的需求不斷增加而且市場潛力巨大，植物藥為主的中藥進入國際市場，必須符合國際植物藥的質量要求及規管。可是一直以來成功在海外註冊的中藥產品寥寥無幾，這都源於海外法規對中藥及植物藥的要求比較嚴謹，尤其重視中草藥安全性、質量性和有效性的標準。本文研究分為兩部分：(一)介紹海內外主要藥典包括中國(CP)、日本(JP)、歐洲(EP)、英國(BP)及美國藥典(USP-NF)，其應用地區廣泛、影響力大，建立的檢測方法水準較高。主要研究各藥典對植物藥及傳統草藥質量標準的概況，及對各國藥典收載的5種基原植物相同生藥與中國藥典的質量檢測標準作比較，為完善中藥質量標準提供借鑒；(二)研究闡述了海外相關政府機構包括歐盟對註冊植物藥或中藥的規管和註冊要點，通過分析歐盟針對草藥藥品的簡化註冊程序 (Simplified registration procedure, SR)，探討其註冊的難度及關鍵問題，以成功註冊之例子，為中藥進入國際市場提供參考，對中藥國際化之路有所啟示。中藥要解決的註冊的限制，需要從提升中藥自身質量標準及國際合作等方面，才能使中藥增強國際競爭力，順利跨越國際技術性註冊的限制。中藥走向國際的過程，是中醫藥與現代西醫藥相互融合的必經階段，最終達到標準統一的過程，二者的不斷融會和貫通，將成為新世紀醫藥產業的一大熱點。 關鍵詞： 中藥規管；植物藥規管；藥典；質量檢測標準；歐盟註冊；簡化註冊程序；中藥國際化 The international market demand for herbal and traditional Chinese medicine is increasing recently. To get marketing authorization from global regulatory bodies, herbal-based Chinese medicine must be complied with international quality and regulatory requirements. However, there are only a few successful cases that Chinese herbal products have been registered overseas due to the high standard of overseas requirements, which emphasis on safety, quality and effectiveness of herbal products. This article is divided into two parts: (a) To introduce the worldwide pharmacopeias including the Chinese Pharmacopeia (CP), Japanese Pharmacopeia (JP), European Pharmacopeia (EP), British Pharmacopeia (BP), the United States Pharmacopeia and the National Formulary (USP-NF). This section aims to collate data from the aforementioned pharmacopoeias and draw comparison on their quality standards and requirements for the five crude drugs / herbal medicine from the same botanical origin for the harmonization of global herbal medicine quality standards, (b) To investigate information of the existing requirements for registration of herbal medicine in the European Union. Through the analysis of a pathway for marketing traditional herbal medicinal products, the “simplified registration” procedure, the key issues and difficulties are discussed and some suggestions with an example are put forward for the registration of Chinese Medicine to enter the international market. To conclude, it is crucial to improve the quality standards of Chinese Medicine to overcome the technical registration problem and facilitate international authorities’ cooperation for enhancing the international competitiveness of Chinese medicine. The internationalization of Chinese medicine will become a hot topic in pharmaceutical industry for the new century. Keywords Regulation of Chinese medicines; Herbal regulation; Pharmacopoeia; Quality testing standards; EU registration; Simplified registration; Internationalization of Chinese medicine

The objective of the following study was threefold: to conduct a homoeopathic drug proving of Acacia xanthophloea 30CH on healthy individuals in order to elucidate the totality of signs and symptoms produced by the drug substance; to analyse the signs and symptoms gathered from the proving, collate the data, and convert the symptoms into materia medica symptoms and rubrics; to compare the symptoms of the proving to the doctrine of signatures. Methodology This proving study was a double-blinded, placebo controlled study. Thirty provers or participants were recruited for the study and the sample size was divided equally between two researchers (A. Gobind and G. Zondi). The sample was randomly divided into two groups, with one group receiving an active substance (verum group) and the other group receiving a placebo (control group). Amongst the 30 provers, 24 participants received verum and six received placebo. Each prover was given a journal to record their symptoms, a pen and nine powders. The duration of this proving study was six weeks including the first week of baseline during which time each prover was required to record their symptoms before taking the proving substance. This procedure was clearly explained to each prover and an information sheet with detail explanation of the proving procedure was provided and informed consent obtained. A thorough case history was taken in the initial consultation and physical examinations to ensure that individuals participating met the inclusion criteria and were healthy. Results Information derived both researchers was combined and the extraction of signs and symptoms then commenced. The symptoms were translated into materia medica and repertory format and graded accordingly. Thereafter the symptoms that emerged from the study were discussed and compared with the doctrine of signatures of Acacia xanthophloea. Provers experienced a wide range of symptoms mentally and emotionally e.g. anger, poor concentration and focus, disconnected feeling, depression, stress, anxiety, antisocial/ aversion to company, tranquillity. A large number of physical symptoms were noted by provers e. g. headaches, ailments of extremities (joint pain, weakness), female related symptoms (irregular menses, decrease/ increase libido etc.), eye symptoms, skin symptoms and general symptoms. The comparison of the symptoms of Acacia xanthophloea 30CH to the doctrine of signatures of the tree Acacia xanthophloea illustrated certain similarities, especially with regard to skin symptoms, eye symptoms, gastrointestinal symptoms and headaches. Conclusion The proving substance Acacia xanthophloea 30CH did produced signs and symptoms when given to healthy individuals as hypothesised. The symptoms when compared to the doctrine of signatures of the acacia xanthophloea tree did show correlation as hypothesised. / M

No description available.

La prima parte del nostro studio riguarda la tecnica LAMP (Loop-mediated isothermal amplification), una tecnica di amplificazione isotermica recentemente inventata (Notomi et al., 2000). Essa presenta notevoli vantaggi rispetto alle tradizionali PCR: non necessita di strumentazioni sofisticate come i termociclatori, può essere eseguita da personale non specializzato, è una tecnica altamente sensibile e specifica ed è molto tollerante agli inibitori. Tutte queste caratteristiche fanno sì che essa possa essere utilizzata al di fuori dei laboratori diagnostici, come POCT (Point of care testing), con il vantaggio di non dover gestire la spedizione del campione e di avere in tempi molto brevi risultati paragonabili a quelli ottenuti con la tradizionale PCR. Sono state prese in considerazione malattie infettive sostenute da batteri che richiedono tempi molto lunghi per la coltivazione o che non sono addirittura coltivabili. Sono stati disegnati dei saggi per la diagnosi di patologie virali che necessitano di diagnosi tempestiva. Altri test messi a punto riguardano malattie genetiche del cane e due batteri d’interesse agro-alimentare. Tutte le prove sono state condotte con tecnica real-time per diminuire il rischio di cross-contaminazione pur riuscendo a comprendere in maniera approfondita l’andamento delle reazioni. Infine è stato messo a punto un metodo di visualizzazione colorimetrico utilizzabile con tutti i saggi messi a punto, che svincola completamente la reazione LAMP dall’esecuzione in un laboratorio specializzato. Il secondo capitolo riguarda lo studio dal punto di vista molecolare di un soggetto che presenza totale assenza di attività mieloperossidasica all’analisi di citochimica automatica (ADVIA® 2120 Hematology System). Lo studio è stato condotto attraverso amplificazione e confronto dei prodotti di PCR ottenuti sul soggetto patologico e su due soggetti con fenotipo wild-type. Si è poi provveduto al sequenziamento dei prodotti di PCR su sequenziatore automatico al fine di ricercare la mutazione responsabile della carenza di MPO nel soggetto indicato. / The first part of the present study concerns the LAMP technique (Loop-Mediated Isothermal Amplification), an isothermal amplification technique recently developed (Notomi et al., 2000). LAMP has many advantages over traditional PCR: it doesn’t require sophisticated instruments like thermal cyclers, it can be performed by unskilled staff, it is a highly sensitive and specific technique and it is very tolerant to inhibitors. All these characteristics make it suitable to be used outside diagnostic laboratories, as POCT (Point-of-care testing), with the advantage of not having to send the sample and obtaining results as accurate as PCR tests and in very short times. We designed and optimized assays to detect bacteria that require a very long time for cultivation or that are not even cultivable. We drew assays for the diagnosis of viral diseases that require to be diagnosed as soon as possible. We developed a test to assess two genetic diseases of the dog and two food contaminating bacteria. All tests were carried out using real-time technique to decrease the risk of cross-contamination. Finally, we developed a colorimetric method for showing results which can be applied to all of the assays we optimized. The second section presents the molecular study of a subject who had myeloperoxidase deficiency at the automated cytochemistry analysis (ADVIA ® 2120 Hematology System). The study was conducted through amplification and comparison of the PCR products obtained from the pathological subject and on two subjects with wild-type phenotype. The products were sequenced using an automated sequencer in order to find the responsible mutation for the MPO deficiency in the indicated subject.

The nasal route is highly promising for the delivery of drugs exerting local effects in the nose or for therapeutic molecules having systemic or CNS effect. This is attributed to the fact that the nasal epithelium is highly vascularized and permeable, which ensures rapid absorption of the drug. The limitation of short residence time of the formulations in the nose and poor bioavailability of hydrophilic drugs could be overcome by the inclusion of bioadhesive agents into formulation. The main objective of this study was to develop novel bioadhesive microspheres and liposomes entrapping the anti-Parkinson drugs ropinirole hydrochloride (RH). The microspheres were prepared via spray drying in combination with chitosan or sodium alginate and the liposomes were prepared using the ethanol-based proliposome method. This study has investigated the potential of powdered mucoadhesive microparticles and liquid liposomes for nasal delivery via Miat® nasal insufflator and nasal spray devices respectively. Optimum mucoadhesive chitosan microparticles were prepared by co-spray drying of chitosan glutamate and ropinirole hydrochloride (90:10 w/w). Characterization studies have revealed that the drug following spray drying was amorphous and the microparticles were spherical and offered drug entrapment efficiency values in the range of 93 - 99%. The optimum formulation provided maximum swelling capacity and slowest drug release. Ex vivo toxicity study using isolated sheep nasal mucosa proved the safety of the optimized formulations for intranasal delivery. Investigation of powder delivery demonstrated that the Miat® nasal insufflator could deliver 90% of the dose with the first puff regardless of the loading weight used to fill the capsule fitted into the nasal device. The spray cloud had elongated shape and was homogenous; this is expected to enhance the impaction of the formulation in the nose following delivery from the nasal device. The properties of sodium alginate microparticles prepared via spray drying were highly dependent on inlet temperature of the spray drier, affecting particle morphology and product yield percent. The best performing particles were obtained when the inlet temperature was 140oC. Alginate to RH ratio had marked effect on particle size (2.60 - 4.37µm), entrapment efficiency (101 – 109%), physical state of the encapsulated RH, and morphology and surface smoothness of the particles as shown by scanning electron microscopy (SEM). In vitro drug release profile showed the amount of sodium alginate in formulations has controlled the rate of drug release. Results revealed that RH-alginate microparticles in 90:10 w/w polymer to drug ratio was the best performing spray dried formulation. Toxicity study proved safety of RH loaded sodium alginate for intranasal delivery. In contrast to RH-chitosan microparticles, particle trajectories was found from the cloud generated from emitted powder and laser diffraction demonstrated that powder was less likely to deposit in the lower respiratory tract owing to particle agglomeration. Ethanol-based proliposome technology produced oligolamellar liposomes from lipid ethanolic solutions as revealed by transmission electron microscopy (TEM). The resultant liposomes entrapped approximately 23.30% of the drug. Using five different bioadhesive agents, inclusion of any of these agents (0.2% w/v) caused a decrease in drug entrapment except for carboxymethyl chitosan which had no effect on the drug entrapment (25.97%). Investigation of aerosolized liposome dispersion using a range of nasal spray devices demonstrated integrity of liposomes were not changed (i.e particle size, Span, and drug entrapment efficiency were unaffected) and RH-loaded liposomes were efficiently delivered from the devices. In conclusion, the finding of this study explored mucoadhesive microspheres entrapped the anti-Parkinson drug, RH, and can potentially be applicable for nasal delivery to enhance nose to brain transport using nasal insufflator for improvement of the symptoms of Parkinson disease and Restless legs syndrome. Similar findings using nasal sprays were found for liposomes. In vivo studies are required in the future to determine the amount of the drug that may reach the blood circulation and brain.

Substituted indoles (2-arylindoles) and related structures are known to exhibit potent anti-cancer activity against human breast cancer cell lines, and a range of other therapeutic targets. This activity, and other factors such as their biological activity, the fact that they are privileged structures, and the presence of the indole nucleus in various commercial anti-cancer drugs led to the choosing of indoles for the current study as a starting point for the development of new treatments against glioma. Investigation began on determining the anti-cancer activity of a variety of indoles against glioma cell lines (1321N1 and U87MG) using a number of different cell-based assays and also to compare them with conventional anti-cancer drugs. The aim was to find potent anti-cancer compound(s), amongst the compounds tested, and by studying its preliminary structure-activity-relationships (SAR), try to determine how the active compound(s) may be exerting their effects. The SAR screening was divided into two main groups: indoles without a 2-aryl group and indoles with a 2-aryl group. The most potent compound identified, and its analogues, were further tested on the non-cancerous SVGp12 cell line to check for specificity of these indoles towards cancer cells, wherein it was found that these compounds were not specific to any particular cell type. Furthermore, activity was also observed for the best lead compound in the glioblastoma short-term culture, IN859, in which it gave a relatively low micromolar IC50 value (400 μM). The results indicated that the anti-cancer activity of these compounds started within 2 h and therefore it was speculated that the mechanism of action of these compounds might work through the generation of reactive oxygen species (ROS). A ROS-detection kit was used to demonstrate this hypothesis, a result which was later corroborated using flow cytometry, and also provided quantitative analysis of the amount of ROS generated. It was further hypothesised that in the cells studied, autophagy was mediated due to excessive ROS generation. This was also confirmed over a similar time course by quantifying the amount of fluorescence generated in the 1321N1 and U87MG cell lines when labelled with acridine orange (a dye used to detect the formation of autophagosomes during autophagy) using flow cytometry. Moreover, the use of an autophagy inhibitor, 3-methyladenine, was shown to inhibit autophagy in these cell lines, again validating this hypothesis. In conclusion, it has been demonstrated that the ability of certain substituted privileged indoles possessing a 2-aryl group and having an attached –OH group to it may have a rapid, deleterious effect on the viability of a primary short term culture (IN859) and glioma cell lines (1321N1 and U87MG). The mechanism of action of these indoles to cause cell death may be via the generation of ROS, leading to cell death initiated by autophagy. Another short separate study was also performed in order to investigate the anti-cancer activity of an anionic host defence peptide, Cn-AMP2, on the above mentioned cell lines. This peptide was found to exhibit a modest cytostatic effect on both the cell lines but at higher concentrations (> 1 mM) and only when the serum concentrations were weaned down from 10 % to 2.5 %.