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Chitosan has proven through the years as a versatile biomaterial to be used in pharmaceutical applications. Its mucoadhesive properties as well as its ability to manipulate the tight junctions in epithelium membranes have qualified it as an effective drug carrier in controlled drug delivery systems. Microparticles or beads as they are forward called in this study have advantages over conventional drug dosage forms because of a large surface to volume ratio and have the ability to target a specific site for drug release. Indomethacin is an anti-inflammatory drug that causes gastrointestinal side effects in conventional immediate-release dosage forms. The goal is to manipulate the drug delivery vehicle to target the intestines/colon as the site for drug delivery and to minimize this side effect. Thus chitosan beads have been chosen as a drug delivery system for indomethacin in this study. Chitosan beads have been prepared through the ionotropic gelation method using tripolyphophate (TPP) as a cross-linking agent. To prepare the most effective bead to encapsulate indomethacin different formulation and system variables (pH of the TPP solution, the concentration of the TPP solution as well as the indomethacin concentration) have been evaluated according to the following parameters: morphology, drug loading capacity and swelling capability. The ideal pH of the TPP solution was determined at 8.7 and the most effective TPP and indomethacin concentration were 5% w/v and 4% w/v respectively. The chitosan concentration was kept at 3% w/v throughout the study. These concentrations were used to examine the effect of pharmaceutical excipients on the indomethacin release from chitosan beads. The effect of the different excipients namely, ExplotabⒽ(0.25% w/v), Ac-Di-SolⓀ (0.5% w/v) and Vitamin C (0.25% w/v), on the morphology, drug loading capacity, swelling capability as well as the drug release of indomethacin chitosan beads (ICB's) were also studied. The excipients were used in the individually above mentioned concentrations and in combination with each other in the same concentrations. These formulations were used in dissolution studies over a period of 6 hours in PBS pH 7.4 solutions. The indomethacin release rate increased when an excipient was added to the formulation and it dramatically increased when the excipients were added in their various combinations, compared to the formulation that did not contain excipients. / Contents: Chitosan -- Controlled drug delivery -- Indomethacin -- Inotropic gelation -- Tripolyphosphate (TPP) -- Explotab® -- Ac-Di-Sol® -- Vitamin C / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Controlled release systems aim at achieving a predictable and reproducible drug release over a desired time period. These systems allow reduced dosing frequency, constant drug levels in the blood, increased patient compliance and decreased adverse effects. In a recent study, Chitosan beads, containing N-trimethyl Chitosan chloride, have shown a potential in the delivery of rifampicin. However, because of inadequate amounts of rifampicin released over 24 hours, incorporation of other pharmaceutical excipients to increase the swelling behaviour of the beads to improve drug release, was considered in this study. Chitosan beads were prepared through ionotropic gelation with tripolyphosphate (TPP) as a crosslinking agent. To increase the porosity if the Chitosan beads Explotab®, Ac-Di-Sol® and vitamin C were added individually to Chitosan solutions at concentrations of 0.1, 0.25 and 0.5 % w/v before adding the mixture to the TPP solution. Swelling and morphology studies were used in the evaluation of the different formulations. The swelling and morphology results were then used to select a set of combination and concentrations of two excipients sand then prepare and characterise beads containing two combinations. The combination formulations and formulations containing single excipients were then loaded with rifampicin. Pure chitosan beads exhibited a higher drug loading capacity (67.49 %) compared to the lowest loading capacity of 41.61 % exhibited by chitosan beads containing a combination of Explotab®, Ac-Di-Sol®.For all the other formulations the drug loading capacity ranged within 48 and 63 %. These formulations were used for dissolution studies over a period of 6 hours at pH 5.60 and 7.40. The dissolution results showed that no chitosan has dissolved at both pH values. A significant amount of rifampicin was, however, released from the beads, especially at pH 7.40. chitosan beads containing vitamin C also exhibited high rifampicin release (48.34 ± 1.00) %) at pH 5.60 compared to the other formulations and this makes vitamin C a potential excipient for enhanced drug release over a wide pH range (both acidic and alkalinic). However, further studies are necessary to optimise the preparation method to minimise drug loss during loading and to improve the drug loading capacity of the beads. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.

In controlled release applications a drug is molecularly dispersed in a polymer phase. In the presence of a thermodynamically compatible solvent, swelling occurs and the polymer releases its content to the surrounding medium. The rate of the drug release can be controlled by interfering with the swelling rate of the beads or by influencing diffusion through the viscosity of the polymer. Beads that contain chitosan were prepared through the ionotropic gelation method where tripolyphosphate (TPP) was used as the crosslinking agent. Beads that consisted of 3% w/v isoniazid (lNH) and 5% w/v chitosan were prepared in a 5% w/v TPP solution (pH 8.7) as the primary beads. To improve the drug loading of chitosan isoniazid beads (ClB) the TPP concentration, pH of the TPP solution and the INH concentrations were altered for maximum drug loading. To increase the porosity of the beads of chitosan beads Explotab® (EXPL), Ac-Di-Sol® (ADS) and Vitamin C (VC) were added individually to chitosan solutions at concentrations of 0.1, 0.25 and 0.5% w/v before adding the mixture to the TPP solution. Morphology, swelling and drug loading studies were used to evaluate the different formulations. After these excipients were added individually they were also added in combinations of two excipients respectively and characterised. From the results of the drug loading studies the beads that contained only chitosan and isoniazid showed a percentage drug loading of (43.92%) which is the best of all the beads that were analyzed. The multi excipient combination of Ac-Di-Sol® and Explotab® showed the best swelling capability at both pH levels. Dissolution studies were conducted on all the formu lations over a period of 6 hours (360 minutes) at pH 5.6 and pH 7.4. From the dissolution results it were clear that no chitosan dissolved at both pH values. The dissolution of single pharmaceutical excipient (SPE) and multi pharmaceutical excipient (MPE) formulations can be arranged in the following order: VC/ADS < VC < ADS/EXPL < ADS < VC/EXPL < CIB < EXPL. Explotab® is a potential excipient for enhanced drug release over a wide pH range. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Controlled release systems aim at achieving a predictable and reproducible drug release profile over a desired time period. These controlled release formulations offer many advantages over conventional dosage forms. These advantages include: reduced dosing intervals, constant drug levels in the blood, increased patient compliance and decreased adverse effects. Complex controlled release formulations such as those with sustained release properties, often require additional steps during the production phase. The cost and economic impact associated with these complex controlled release dosage formulations often outweigh the short term benefits. Thus the development of an economic method to produce controlled release particles is of great importance especially in third world countries. In controlled release formulations the drug is often equally dispersed throughout a polymer matrix. In the presence of a thermodynamically compatible solvent, swelling occurs and the polymer releases its content to the surrounding medium. The rate of drug release can be controlled by interfering with the amount of swelling and rate of diffusion by manipulating the viscosity of the polymer matrix. Chitosan is an ideal candidate for controlled drug delivery through matrix release systems. It is a biodegradable polymer with absorption-enhancing properties. Cross-linking chitosan with different cross-linking agents allow the preparation of beads. Beads are frequently used in controlled release dosage forms as they are very flexible in dosage form development and show various advantages over single unit dosage forms. Because beads disperse freely in the gastrointestinal tract they maximize drug absorption, reduce fluctuation in peak plasma, and minimize potential side effects without lowering drug bio-availability. Chitosan beads and excipient containing chitosan beads were prepared and investigated as possible controlled release formulations. Pyrazinamide was chosen as the model drug. Chitosan beads and excipient containing chitosan beads were prepared by ionotropic gelation in tripolyphosphate. In this study chitosan/pyrazinamide beads containing pharmaceutical excipients (Ascorbic acid, Explotab and Ac-Di-Sol) were produced. The excipients were added individually and in combinations to the chitosadpyrazinamide dispersion and the beads were characterized on the basis of their morphology, solubility, fiability, drug loading capacity and swelling behaviour, as well as drug release (dissolution properties). The drug loading of the pyrazinarnide loaded chitosan beads, was 52.26 % 0.57%. It was noted that the inclusion of excipients in the beads resulted in an increase in drug loading with the combination of Ascorbic acid and Ac-Di-Sol giving the highest drug loading of 67.09 ± 0.22%. It was expected that the addition of the pharmaceutical excipients would lead to a sustained release of pyrazinamide. Dissolutions studies, however, revealed a burst release in both phosphate buffer solution (PBS) pH 5.60 and 7.40 over the first 15 minutes and the curve reached a plateau after 30 minutes. Thus, apparently the inclusion of the pharmaceutical excipients did not contribute to a sustained release of pyrazinamide over the tested period of six hours. In future studies the dissolution time can possibly be extended to a period of 24 hours. It might be possible for the remaining drug (approximately 40%) in the beads to be released over the extended period. Other polymers can also be investigated to control the release of pyrazinamide. Further studies are, however, necessary to investigate this possibility in the future. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Il lavoro affronta il tema dell’oggetto e dell’ambito di tutela del brevetto biotecnologico, con particolare riferimento al brevetto di sequenze di DNA. L’importanza crescente delle biotecnologie, in settori come quello agroalimentare, e il peso notevole degli investimenti che la ricerca in questo ambito richiede, impongono il ricorso ad un efficace modello di tutela che incentivi il progresso tecnologico, senza, tuttavia, ostacolare la ricerca derivata. A partire da questa premessa, il lavoro mette in luce, in primo luogo, le problematiche fondamentali poste dalla disciplina del brevetto per invenzione industriale. Successivamente, in una prospettiva comparata, lo studio si occupa dell’oggetto del brevetto biotecnologico e dei requisiti di brevettabilità, attraverso un esame della disciplina, della dottrina e della più recente giurisprudenza europea e statunitense. Con riferimento all’Europa, in particolare, l’analisi si concentra attorno alla disciplina posta dalla direttiva 98/44/CE sulla tutela delle invenzioni biotecnologiche. Il lavoro si articola, quindi, attorno al tema dell’estensione del brevetto biotecnologico, attraverso l’esame dei diversi paradigmi di tutela possibili e ponendo l’accento sulle strategie per un efficace contemperamento dei diversi interessi coinvolti. / This work relates to biotechnological inventions, specifically concerning patentability and scope of protection of DNA sequences. Biotechnology is of utmost importance in many sectors, not least in the agro food one. Moreover, this is a high capital intensive field of study, where downstream research is mainly based on upstream results. Consequently, it is extremely important to provide a system of protection aimed at spurring innovation without preventing subsequent research. This considered, the work highlights the general legal framework on patents. It then focuses on the object of biotech patents and patentability requirements, through a comparative study of the US and the European legal system and on the most recent case law. Specifically concerning Europe, an in depth analysis of the 98/44/CE directive is carried out. The research work then focuses on the main models of patent protection, with the aim of emphasizing strategies to collect the different and diverging interests arising over the issue. ​

The English-language translations of Jorge Luis Borges’s Spanish-language works undertaken by the author and Norman Di Giovanni went above and beyond what is generally perceived as acceptable in traditional Western practices. Their work, together with Borges’s thoughts on translation itself, garnered criticism from within Western Translation Studies for its rejection of the status of the original text and the blurring of the distinction between author and translator. Yet the pair’s actions and Borges’s views on translation cease to appear scandalous under the light of Buddhist philosophy, particularly through the use of the Buddhist principles that all phenomena are impermanent and interdependent. This thesis will seek to use these ideas to legitimize the actions of Borges and Di Giovanni. To do so, it will trace the history of opposing and convergent theories from Western philosophy and describe our Buddhist concepts in detail. In order to better understand Borges, it will examine the array of philosophies that influenced the writer and how they both align themselves and differ from Buddhist ideas. This thesis will end by directly applying impermanence and interdependence to the translation practices of Borges and Di Giovanni and considering what potential effect legitimacy for such practices would have on translation overall.

Sebbene la presenza dei figli degli migranti stia assumendo sempre maggior rilievo anche in Italia la ricerca ha posto poca attenzione alle loro scelte di consumo mediale e all’appropriazione dei media come risorse sociali ed ambientali. La tesi si focalizza sul caso delle giovani donne di origine araba per indagare il ruolo giocato dal consumo di notizie nella cornice più complessa dei processi di negoziazione di identità. Un focus è riservato alle tre dimensioni di appartenenze, partecipazione e trasmissione culturale tra generazioni – in relazione alle madri e ai coetanei. Un’indagine, a livello più “macro”, indaga le possibili implicazioni per il dialogo interculturale. Attraverso la raccolta di quarantotto storie di vita un primo livello di analisi diacronico indaga presenza e intensità del consumo di news nelle fasi della vita per comprendere se possa rappresentare un rito di passaggio all’età adulta, mentre una seconda pista cerca di comprendere come esso si leghi alla questione del sentirsi “cittadini”, in termini di riconoscimento, appartenenza e per scoprire se il consumo di news possa diventare una risorsa per essere soggetti attivi nella sfera pubblica. Tutte le giovani donne di origine araba vivono a Milano, hanno tra i diciotto e i trentadue anni e differiscono per le variabili di 1) nascita o arrivo in Italia dopo i 6 anni; 2) attivismo e 3) religiosità (musulmane, copte ortodosse, atee). / Although the presence of migrants’ sons and daughters is gaining more and more importance also in Italy, the research have not given special attention to their choices concerning media consumption and to the appropriation of the media as social and environmental resources. This thesis is focused on the case of young women of Arab origin in order to investigate the intersections between news consumption and the negotiation of the social identity. A first focus is on three dimensions: participation, belonging and cultural transmission – in comparison with mothers and peers. A second “macro” level of the research investigates the implications as regard to intercultural dialogue. Through the collection of forty-eight life histories, a first level of diachronic analysis investigates the presence and the intensity of news consumption in different stages in order to understand if it could be a rite of passage to the adulthood, while a second track tries to understand how this is connected to the feeling of being “citizens”, in terms of identification, belonging and to investigate if news consumption may be a resource to be active citizens in the public sphere. All young women of Arab origin live in Milan, they are between eighteen and thirty-two years old, and differ in variables 1) they were born or arrived in Italy since they were 6 years old, 2) activism and 3) religion (Muslims, Coptic Orthodox or atheists).

La presente ricerca di dottorato si pone tre principali obiettivi: 1) studiare i processi di integrazione dei migranti, intesi nella loro bidirezionalità, multidimensionalità e processualità, con un focus specifico sulle pratiche di cittadinanza; 2) elaborare un set di indicatori al fine di misurare le pratiche di cittadinanza dei migranti nelle società riceventi; 3) identificare, tramite un modello di regressione logistica, la probabilità di essere un cittadino attivo considerando una serie di variabili indipendenti, quali classe di età, genere, background migratorio ecc. La ricerca è stata condotta mediante l’utilizzo combinato di metodi qualitativi e metodi quantitativi. Nello specifico in Svezia, paese scelto come caso studio, sono state realizzate 23 interviste semi-strutturate ad attori chiave della società, tra i quali rappresentanti istituzionali nazionali (Ministero del Lavoro), regionali e locali, sindacati, ONG, equality body, associazioni di migranti e migranti stessi. Successivamente, anche sulla base delle risultanze di questa fase, è stato elaborato un set di indicatori volto a misurare la partecipazione dei cittadini e, utilizzando tali indicatori, si è proceduto all’analisi secondaria dei dati della European Social Survey Round 6. / Citizenship practices are a central issue in migration studies, but not yet adequately reflected in the social sciences. In line with this, the three main objectives of this work may be summarised as follows. The first objective is to offer an analytical definition of citizenship practices capable of encompassing, both analytically and empirically, different forms of participation and at different levels (local, national, international, and transnational). The second is to elaborate a comprehensive set of indicators able to measure the level of migrant participation. Finally, an additional objective is to identify migrant-specific patterns of participation in Europe, with a particular focus on Sweden. The findings of my work are the result of the combined use of both qualitative and quantitative research methods. I conducted 23 semi-structured interviews with key actors of Swedish society (institutional actors, representatives of NGOs and of equality bodies, representatives of migrant associations). In the light of the results of the desk research and interviews, I have constructed a set of 25 indicators aiming at measuring the level of migrant participation, in the political, socio-economic and cultural-religious fields. Thus, using these indicators, I analyse data of the European Social Survey Round 6.

Cystic Fibrosis (CF) is an autosomal recessive disease that arises from mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. The deletion of phenylalanine-508 (ΔF508-CFTR) is the most prevalent CF mutation and results in a misfolded protein that fails to exit the endoplasmic reticulum (ER). Previous studies demonstrated that mutation of a di-arginine based ER retention motif (R553AR555) in the first nucleotide binding domain (NBD1) rescues the trafficking defect of ΔF508-CFTR. We hypothesized that if the R553AR555 motif mediates retention of the ΔF508-CFTR protein, peptides that mimic this motif should antagonize mistrafficking mediated by aberrant exposure of the endogenous R553AR555 motif. We generated a peptide bearing the R553AR555 motif (CF-RXR) and conjugated it to the cell penetrating peptide Tat (CPP-CF-RXR) to facilitate intracellular delivery and investigated its efficacy in rescuing the mistrafficking and function of ΔF508-CFTR. Using a variety of biochemical and functional assays we demonstrate that the CPP-CF-RXR peptide is effective at increasing surface expression of ΔF508-CFTR in baby hamster kidney (BHK) and human embryonic kidney (HEK) cell lines. Furthermore, the increased surface expression is accompanied by an increase in its functional expression as a chloride channel. Using Ussing chamber assays, we demonstrate that the CPP-CF-RXR peptide improved ΔF508-CFTR channel function in respiratory epithelial tissues obtained from CF patients. Additionally, we investigated the effects of small molecules on mediating biosynthetic rescue of a ΔF508-CFTR construct bearing the additional mutations R553K and R555K (ΔFRK-CFTR) to inactivate the R553AR555 motif. Interestingly, mutation of the R553AR555 motif exerts an additive effect with correctors VRT-325 and Corrector 4a. Taken together, our data suggests that abnormal accessibility of the RXR motif present in NBD1 is a key determinant of the mistrafficking of the major CF causing mutant.