Braunschweig, Techn. University, Diss., 1998.

Marburg, Univ., Diss., 2003. / Computerdatei im Fernzugriff.

Marburg, Universiẗat, Diss., 2003.

Universiẗat, Diss., 2003--Marburg.

Alginate is a well-known naturally-derived biomaterial that has been widely used in preparing microparticles for drug delivery and in preparing scaffolds for tissue engineering. Despite desirable properties, alginate has been shown to activate inflammatory cells in vivo. The mechanisms are still unclear. In this thesis, the mechanism by which alginate caused innate immune responses was investigated in vitro by using RAW264.7 cells, a macrophage-like cell line. The NF-(kappa)B pathway, an important signaling pathway in macrophages, has been tracked to identify cellular responses. The secretion of cytokines IL-1(beta), IL-6, IL-12(p40) and TNF-(alpha) was quantified to determine the activation outcomes. Also the interaction between alginate and serum was studied. Experimental results indicated that alginate induced the activation of RAW264.7 cells with a time and dose dependent behavior. Like lipopolysaccharide, a bacterial product and known activator of innate immunity, alginate induced macrophage activation through the NF-(kappa)B pathway and eventually led to detectable IL-1(beta), IL-6 and TNF-(alpha) cytokine secretion. Serum influenced alginate recognition by macrophages in an unknown mechanism. Also, alginate promoted cell survival in a nutrition starvation condition. These results revealed in vitro alginate stimulation, and provided much information for further research. / Thesis / Master of Applied Science (MASc)

No description available.

No description available.

A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the Degree of Master of Science in Medicine (Pharmacy), Johannesburg / This thesis presents a multifaceted approach which comprehensively describes the design of novel drug delivery polymeric complexes through the application of innovative crosslinking reactions. These reactions have been built on the statistical and mathematical principles governing the technique of Design of Experiments. At the outset, pertinent aspects covering the importance of rate-controlled drug delivery in achieving superior therapeutics is presented. In addition, the fundamental mechanisms which regulate the complex behaviour of polymeric materials are outlined, placing emphasis on the mathematical models which demonstrate the critical need to be able to synchronize the processes of matrix hydration, relaxation, disentanglement, erosion and dissolution. Initially, the Plackett-Burman Design was evaluated to develop a crosslinked polymeric oilisphere device for the in vitro site-specific delivery of Mentha piperita oil. This design proved to be highly successful in rapidly identifying the appropriate release rate-modifying variables through the application of stepwise regression optimization and Artificial Neural Networks. / IT2018

Duisburg, Essen, Universiẗat, Diss., 2004.

A cost effective approach to the delivery of therapeutic gene products in vivo is to immunoprotect genetically-engineered, universal, non-autologous cells in biocompatible microcapsules before implantation. Myoblasts may be an ideal cell type for encapsulation due to their inherent ability to differentiate into myotubes, thereby eliminating the problem of cell overgrowth within the capsular space. To evaluate the interaction between the differentiation program and the secretory activity of the myoblasts within the microcapsule environment, we transfected C2C12 myoblasts to express human growth hormone and followed their expression of muscle differentiation markers, such as creatine phosphate kinase (CPK) protein and up-regulation of muscle-specific genes (ie. myosin light chains 2 & 1/3, Troponin I slow, Troponin T, myogenin and MyoD1). As the transfected myoblasts were induced to differentiate for up to two weeks, their myogenic index (i.e. the percentage of multinucleate myoblasts) increased from 0 to ~50%. Concomitantly, up-regulation of differentiation marker RNA levels, and as much as a 23-fold increase in CPK activity, were observed. After encapsulation and the induction of differentiation, the myoblasts showed a lag phase of ~3 days before an increase in CPK was observed, although the level of CPK activity increased by as much as 63-fold. The myogenic index of the encapsulated cells remained at zero. The rate of human growth hormone secretion was relatively constant throughout the two-week differentiation period, at an average of 7.78 x 10^-2 ng hGH per hour per (mu)g protein, however, human growth hormone secretion was slightly decreased by about twofold during the differentiation of encapsulated myoblasts. In conclusion, the differentiation of myoblasts into myotubes is retarded after encapsulation while the secretion of a recombinant product is slightly reduced. Further studies are necessary to elucidate the cause of this atypical differentiation pattern such that the proliferation and differentiation of the encapsulated myoblasts may be optimized to provide a stable vehicle for gene delivery. / Thesis / Master of Science (MS)