Controlled drug delivery devices provide numerous advantages such as reduced side effects, higher therapeutic efficiency and improved patient compliance. Biodegradable polymer has become the most important material for controlled drug delivery device because of the excellent biocompatibility and tunable physicochemical properties. Biodegradable polymeric drug delivery devices are usually processed into various types of micro-particles due to the ease of fabrication and administration. However, controlling the drug release kinetics of these microparticles is still a challenge. One important reason is that drug release kinetics is significantly influenced by the microstructure of drug delivery devices, which is difficult to control. 　Microfluidic method is a group of technologies involved in the manipulation of fluids using channels in the scale of micrometers. Microfluidic method is particularly useful in controlling the structure of micro-droplets and generating homogeneous droplets. Therefore, microfluidics suggests great potential in controlling microstructures of drug delivery devices and drug release kinetics. 　In this study, biodegradable polymer based controlled drug delivery devices were fabricated using microfluidic method. Various types of microstructures were developed such as microspheres, core-shell microspheres, hollow microspheres and hydrogel microspheres. The results showed that microstructures were well controlled by fluid flow rates and geometries of capillary microfluidic devices. Both hydrophobic and hydrophilic drugs could be delivered by choosing drug delivery devices with suitable microstructures. 　Drug release kinetics of biodegradable polymeric microspheres has been studies a lot, yet complete understanding is still to be achieved. The diameter is an important factor which contributes to the drug release kinetics. However, the influence of diameter has not been systemically studied because monodisperse microspheres are difficult to obtain. Using microfluidic method, monodisperse PLGA microspheres with different diameters were fabricated to study the influence of diameter on drug release kinetics. It was found that diameter only influence the duration of the first phase (lag phase) in drug release process and smaller microspheres exhibited shorter lag phase. The relatively faster expansion of smaller microspheres was found to be responsible for the size effect by monitoring physicochemical changes during drug release. 　Rifampicin, a broad-spectrum antibiotic, was encapsulated by PLGA microspheres and PLGA-alginate core-shell microspheres. The long-term antimicrobial effects of drug loaded microspheres were investigated by drug release test and antimicrobial test against Staphylococcus aureus. The results showed that drug delivery devices could provide antimicrobial effect for more than one month. These drug delivery devices show potential in applications of controlled drug delivery and long-term antimicrobial therapy. 　In conclusion, drug delivery devices with different microstructures were fabricated using microfluidic method. The diameter of PLGA microspheres only influence the first phase of drug release profile (lag phase) and smaller microspheres exhibited shorter lag phase. The size effect is due to the relatively faster expansion rate of smaller microspheres. Rifampicin loaded PLGA microspheres and PLGA-alginate core-shell microspheres could provide sustained release of rifampicin for more than one month. The released rifampicin was able to inhibit the growth of Staphylococcus aureus. The controlled drug delivery devices presented showed great potential in long-term antimicrobial applications. / published_or_final_version / Orthopaedics and Traumatology / Doctoral / Doctor of Philosophy

by Mei Choi Tang. / Thesis submitted in 1997. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references. / Abstract also in Chinese. / Chapter Chapter 1. --- Introduction --- p.1-22 / Chapter Chapter 2. --- PAE studies for antimicrobial combinations using the Fractional Maximal Effect method (FME method) --- p.23-64 / Chapter Chapter 3. --- Effect of sequential antibiotic administration on the postantibiotic effect exhibited by an antimicrobial combination: A case for the combination of rifampin and tobramycin against E.coli ATCC 25922 --- p.65-84 / Chapter Chapter 4. --- Effect of antimicrobial resistance to the components of an antimicrobial combination: A pilot study with piperacillin and gentamicin against Ps. aeruginosa --- p.85-100 / Chapter Chapter 5. --- Conclusions --- p.101-106 / Appendix I --- p.107-113 / Appendix II --- p.114-116 / Appendix III --- p.117-120 / Appendix IV --- p.121-138 / Appendix V --- p.139-153

Indiana University-Purdue University Indianapolis (IUPUI) / Root canal therapy is a recommended treatment for apical periodontitis. Root canal failure can occur as a result of microbial leakage. Resilon, a resin based root canal obturating cone material introduced in 2004 attempts to minimize leakage by a unique bonding method of the resin sealer to both the core material and to the dentin of the canal walls. Resilon has no bactericidal or antimicrobial effect15. Furthermore, it has been shown that Resilon is susceptible to alkaline and enzymatic hydrolysis as well as bacterial degradation.73, 184-186 It has been suggested that Resilon may be susceptible to degradation by microorganisms found in the infected root canal space. This work focuses on the susceptibility of root canal obturating materials to be degraded by endodontic pathogens seen in root canal treated teeth with apical periodontitis. The aim of this study was to determine if Resilon could be degraded by selected pathogenic bacteria found in the infected root canal system, and if this degradation is more severe than with gutta-percha, a conventional obturating material. P. intermedia, E. faecalis and P. aeruginosa, known endodontic pathogens were inoculated on discs of obturating material (Resilon or gutta-percha) mounted on a platform and placed in wells containing TSB incubated at 37°C under aerobic conditions. The discs were polished, examined by SEM, profilometry, and elemental analysis prior to inoculation to establish a baseline, and were then re-examined by these methods one month after inoculation. The overall results were inconclusive; and using these methods it cannot be determined that the selected bacteria can degrade Resilon. An ideal future study would utilize SEM with gold coated samples as well as atomic force microscopy to evaluate for changes in topographical features of these obturating materials. A notable finding was that Resilon turns black when exposed to bacteria, and the significance of this finding should be addressed in future studies.