Made available in DSpace on 2014-12-17T14:16:27Z (GMT). No. of bitstreams: 1 AliceRO_DISSERT.pdf: 2104659 bytes, checksum: 208850f5293dd4764037ec4c490d3636 (MD5) Previous issue date: 2011-12-19 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Methotrexate (MTX) is a drug used in the chemotherapy of some kind of cancers, autoimmune diseases and non inflammatory resistant to corticosteroids uveits. However, the rapid plasmatic elimination limits its therapeutic success, which leads to administration of high doses to maintain the therapeutic levels in the target tissues, occurring potential side effects. The aim of this study was to obtain spray dried biodegradable poly-lactic acid co-glycolic acid (PLGA) microparticles containing MTX. Thus, suitable amounts of MTX and PLGA were dissolved in appropriate solvent system to obtain solutions at different ratios drug/polymer (10, 20, 30 and 50% m/m). The physicochemical characterizing included the quantitative analysis of the drug using a validate UV-VIS spectrophotometry method, scanning electron microscopy (SEM), infrared spectrophotometry (IR), thermal analyses and X-ray diffraction analysis. The in vitro release studies were carried out in a thermostatized phosphate buffer pH 7.4 (0.05 M KH2PO4) medium at 37?C ? 0.2 ?C. The in vitro release date was subjected to different kinetics release models. The MTX-loaded PLGA microparticles showed a spherical shape with smooth surface and high level of entrapped drug. The encapsulation efficiency was greater then 80%. IR spectroscopy showed that there was no chemical bond between the compounds, suggesting just the possible occurrence of hydrogen bound interactions. The thermal analyses and X-ray diffraction analysis shown that MTX is homogeneously dispersed inside polymeric matrix, with a prevalent amorphous state or in a stable molecular dispersion. The in vitro release studies confirmed the sustained release for distinct MTX-loaded PLGA microparticles. The involved drug release mechanism was non Fickian diffusion, which was confirmed by Kornmeyer-Peppas kinetic model. The experimental results demonstrated that the MTX-loaded PLGA microparticles were successfully obtained by spray drying and its potential as prolonged drug release system. / O metotrexato (MTX) ? um f?rmaco utilizado na quimioterapia de alguns tipos de c?ncer, doen?as autoimunes e uve?tes n?o inflamat?rias resistentes aos corticoster?ides. No entanto, sua r?pida elimina??o plasm?tica limita o sucesso terap?utico, levando ? necessidade de altas doses para manuten??o da concentra??o efetiva no tecido alvo, ocasionando o potencial surgimento de rea??es adversas. O objetivo principal desse estudo foi obter um sistema microparticulado biodegrad?vel ? base de ?cido poli (?cido l?tico-co-?cido glic?lico) (PLGA) por spray drying para libera??o prolongada do MTX. Para isso, quantidades distintas de MTX e PLGA foram dissolvidas em sistema solvente adequado para obter solu??es com diferentes propor??es de f?rmaco em rela??o ao pol?mero (10, 20, 30 e 50% m/m). A caracteriza??o f?sicoqu?mica incluiu an?lise quantitativa do f?rmaco incorporado na matriz polim?rica por espectrofotometria UV-VIS em 303nm previamente validada, microscopia eletr?nica de varredura (MEV), espectrofotometria de infravermelho (IV), an?lises t?rmicas e difra??o de raios-X (DRX). O perfil de libera??o in vitro do f?rmaco nas micropart?culas foi realizado em tamp?o fosfato (0.05 M KH2PO4) em banho termostatizado 37 ?C ? 0.2 ?C. Os dados obtidos do estudo de libera??o in vitro foram submetidos a diferentes modelos cin?ticos de libera??o. As micropart?culas de PLGA contendo o MTX apresentaram a forma esf?rica, uniforme, com superf?cie aparentemente lisa. O n?vel de efici?ncia de encapsula??o foi superior a 80%. A espectroscopia na regi?o do infravermelho demonstrou que n?o ocorreu liga??o qu?mica entre os componentes dos sistemas, no entanto foi observado forte intera??o entre o MTX e PLGA indicando prov?vel ocorr?ncia de pontes de hidrog?nio. An?lise XII t?rmica e DRX demonstraram que o MTX est? distribu?do na matriz polim?rica com a preval?ncia do estado amorfo ou em dispers?o molecular. O estudo de libera??o in vitro confirmou o perfil de libera??o prolongada para as diferentes micropart?culas. O mecanismo de libera??o envolvido foi por difus?o n?o Fickiana, ao qual foi determinado a partir do modelo cin?tico de Kornmeyer- Peppas. Os resultados experimentais demonstraram o sucesso na obten??o das micropart?culas de PLGA contendo o MTX por spray drying e seu potencial como sistema de libera??o prolongada do f?rmaco.

Das bei der Sanierung von großen segmentalen Knochendefekten bestehende Risiko einer fremdkörperassoziierten Infektion soll durch die Integration eines Wirkstofffreisetzungssystems in ein bestehendes textiles Knochenimplantat gemindert werden. Durch Immobilisierung des Wirkstoffs in eine degradierbare Polymermatrix wird eine zeitlich verzögerte Freisetzung bewirkt. Als Wirkstofffreisetzungssystem wird die Kombination von Polylactid (PLA) bzw. Poly(Lactid-co-Glycolid) (PLGA) als Matrixpolymer mit dem Antibiotikum Gentamicin als Wirkstoff untersucht, welches durch Beschichtung der textilen Scaffolds mittels Dip-Coating eingebracht werden soll. Es stehen die drei Beschichtungsmethoden „Suspension“, „Emulsion“ und „Schichtaufbau“ zur Auswahl, die jeweils über eigene Parameter zur Beeinflussung des Freisetzungsprofils verfügen. Die Methode „Suspension“ und die damit verbundenen Einflussfaktoren Korngröße, Korngrößenverteilung sowie Masseanteil des Antibiotikums und Schichtdicke der aufgetragenen Polymerschicht wurde als die günstigste herausgearbeitet. Im Teil II dieser Arbeit wird diese soweit optimiert, dass nahezu über den gesamten geforderten Zeitraum die festgelegte notwendige Dosierung aufrechterhalten werden kann. Erste in vitro Versuche weisen auf eine gute Zellverträglichkeit sowie eine ausreichende mikrobielle Wirksamkeit hin. / To reduce the risk of infection in the treatment of long bone defects, a novel embroidered bone implant is to be provided with an antibiotic drug delivery system. Prolonged and controlled drug release can be achieved by coating the thread material with antibiotics incorporated in a degradable polymer matrix. The chosen drug delivery system is composed of polylactide acid (PLA) or poly(lactide-co-glycolide) acid (PLGA) as matrix polymer and the antibiotic gentamicin. It is integrated into the textile structure by dip-coating providing the three different methods suspension, emulsion and layered. Each method bears its appropriate parameters to influence the releasing profile. The suspension-method and its parameters grain size and grain size distribution as well as mass fraction of the antibiotic and the coating thickness could be proved as the most feasible. In part II of this essay the chosen coating set-up gets optimized so that a drug release nearly along the whole required term can be achieved. Preliminary in vitro studies show a good cell tolerance besides a sufficient microbial efficacy.

Das bei der Sanierung von großen segmentalen Knochendefekten bestehende Risiko einer fremdkörperassoziierten Infektion soll durch die Integration eines Wirkstofffreisetzungssystems in ein bestehendes textiles Knochenimplantat gemindert werden. Durch Immobilisierung des Wirkstoffs in eine degradierbare Polymermatrix wird eine zeitlich verzögerte Freisetzung bewirkt. Als Wirkstofffreisetzungssystem wird die Kombination von Polylactid (PLA) bzw. Poly(Lactid-co-Glycolid) (PLGA) als Matrixpolymer mit dem Antibiotikum Gentamicin als Wirkstoff untersucht, welches durch Beschichtung der textilen Scaffolds mittels Dip-Coating eingebracht werden soll. Es stehen die drei Beschichtungsmethoden „Suspension“, „Emulsion“ und „Schichtaufbau“ zur Auswahl, die jeweils über eigene Parameter zur Beeinflussung des Freisetzungsprofils verfügen. Die Methode „Suspension“ und die damit verbundenen Einflussfaktoren Korngröße, Korngrößenverteilung sowie Masseanteil des Antibiotikums und Schichtdicke der aufgetragenen Polymerschicht wurde als die günstigste herausgearbeitet. Im Teil II dieser Arbeit wird diese soweit optimiert, dass nahezu über den gesamten geforderten Zeitraum die festgelegte notwendige Dosierung aufrechterhalten werden kann. Erste in vitro Versuche weisen auf eine gute Zellverträglichkeit sowie eine ausreichende mikrobielle Wirksamkeit hin. / To reduce the risk of infection in the treatment of long bone defects, a novel embroidered bone implant is to be provided with an antibiotic drug delivery system. Prolonged and controlled drug release can be achieved by coating the thread material with antibiotics incorporated in a degradable polymer matrix. The chosen drug delivery system is composed of polylactide acid (PLA) or poly(lactide-co-glycolide) acid (PLGA) as matrix polymer and the antibiotic gentamicin. It is integrated into the textile structure by dip-coating providing the three different methods suspension, emulsion and layered. Each method bears its appropriate parameters to influence the releasing profile. The suspension-method and its parameters grain size and grain size distribution as well as mass fraction of the antibiotic and the coating thickness could be proved as the most feasible. In part II of this essay the chosen coating set-up gets optimized so that a drug release nearly along the whole required term can be achieved. Preliminary in vitro studies show a good cell tolerance besides a sufficient microbial efficacy.

A miniaturização de elementos mecânicos como pontes e vigas por meio de processos de fabricação antes utilizados exclusivamente em microeletrônica, levou ao desenvolvimento de sensores físicos que hoje são onipresentes no dia-dia. Desses elementos, o cantilever, ou viga engastada, é a estrutura mais simples, porém, quando miniaturizado em escala micrométrica, suas propriedades mecânicas como frequência de ressonância e curvatura são muito sensíveis a eventos que ocorrem em sua superfície. Stresses superficiais mínimos, como aqueles gerados pela adsorção de monocamadas na superfície, causam deflexões em uma escala que é facilmente medida com técnicas relativamente simples. Além disso, a frequência de ressonância que é característica da estrutura, é proporcional à mudanças relativas de massa do dispositivo, sendo possível assim, a medida de massa em baixíssimas escalas. Nesse trabalho, estudou-se a utilização do microcantilever como uma plataforma para estudo de materiais, mais especificamente, materiais poliméricos. Depositando-se uma quantidade muito pequena de polímero na superfície de um microcantilever de silício, essa estrutura se curvará devido à diferenças nos coeficientes de expansão térmico entre os materiais. Medindo-se essa curvatura em função da temperatura, é possível detectar eventos térmicos que esse polímero venha sofrer. Esse efeito foi utilizado para estudar como a absorção de água afeta o evento térmico de transição vítrea do polímero PLGA. Observou-se que essa caracterização é muito mais rápida utilizando microcantilever se comparado às técnicas convencionais, além de ser também, muito sensível às variações de quantidade de água. Para a realização desses estudos, foi desenvolvido um sistema de medidas que utiliza pick-up de CDROM, retirada de um leitor comum, para medir a deflexão dos dispositivos. Esse tipo de arranjo é capaz de medir diferenças de nanômetros de deslocamento com um custo mínimo. Explorou-se a capacidade de controle de temperatura e leitura de deslocamento aplicando-se a técnica de modulação de temperatura nos estudos de eventos térmicos do PLGA. Observou-se que a modulação de temperatura é aplicável a esse tipo de medida e resultados muito semelhantes àqueles obtidos com técnicas convencionais são obtidos com uma quantidade muito menor de material. Como essas medidas foram realizadas utilizando sensores comerciais, realizamos a construção de matrizes de cantileveres no laboratório para demonstrar completo desenvolvimento desse tipo de plataforma de sensor. Empregando um polímero fotossensível relativamente novo para o desenvolvimento dessas matrizes, às utilizamos para caracterizações das propriedades mecânicas desse material. / The miniaturization of mechanical elements such as bridges or beams employing fabrication process previously used exclusively in microelectronics, resulted in the development of ubiquous physical sensors used today. The cantilever, or single supported beam is the most simple of these structures, but, when miniaturizated in the micrometer scale, the properties of the structure are highly dependent on events that takes place in its surface. Minimal superficial stresses like the ones generated by the adsorption of monolayers causes deflection of the structure in a scale that are easily measured by simple techniques. Moreover, the resonant frequency is highly dependent on relative mass changes of the device, making it a very sensitive microbalance. In this work, it was studied the application of microcantilevers as a platform for the study of materials properties, more specifically thermal analysis of polymeric material. When a very small quanitity of polymer is deposited in the surface of a silicon microcantilever, the structure will bend due to the mismatch of thermal expansion between the materials. Measuring the beam curvature in function of temperature enables the detection of thermal events suffered by the polymer. This effect was used to measure how the water absorption by the polymer affect the glass transition thermal event of the PLGA polymer. It was observed that this technique is faster if compared to traditional thermal chracterization techniques. To enable those characterizations, it was developed a measurement systems based on CDROM pick-up that can read the nanometer scale cantilever deflection with a minimum cost. The full capabilities of this system was then used to apply temperature modulation to the thermal studies of PLGA, we observed similar responses if compared to traditional approaches but with much less material use. Comercial sensors were used on these characterization, but, to present complet domain of cantilever sensor platform, we developed a fabrication process of polymeric cantilever array at the lab. These arrays were then used to extract mechanical information about the polymer used in its construction.

A miniaturização de elementos mecânicos como pontes e vigas por meio de processos de fabricação antes utilizados exclusivamente em microeletrônica, levou ao desenvolvimento de sensores físicos que hoje são onipresentes no dia-dia. Desses elementos, o cantilever, ou viga engastada, é a estrutura mais simples, porém, quando miniaturizado em escala micrométrica, suas propriedades mecânicas como frequência de ressonância e curvatura são muito sensíveis a eventos que ocorrem em sua superfície. Stresses superficiais mínimos, como aqueles gerados pela adsorção de monocamadas na superfície, causam deflexões em uma escala que é facilmente medida com técnicas relativamente simples. Além disso, a frequência de ressonância que é característica da estrutura, é proporcional à mudanças relativas de massa do dispositivo, sendo possível assim, a medida de massa em baixíssimas escalas. Nesse trabalho, estudou-se a utilização do microcantilever como uma plataforma para estudo de materiais, mais especificamente, materiais poliméricos. Depositando-se uma quantidade muito pequena de polímero na superfície de um microcantilever de silício, essa estrutura se curvará devido à diferenças nos coeficientes de expansão térmico entre os materiais. Medindo-se essa curvatura em função da temperatura, é possível detectar eventos térmicos que esse polímero venha sofrer. Esse efeito foi utilizado para estudar como a absorção de água afeta o evento térmico de transição vítrea do polímero PLGA. Observou-se que essa caracterização é muito mais rápida utilizando microcantilever se comparado às técnicas convencionais, além de ser também, muito sensível às variações de quantidade de água. Para a realização desses estudos, foi desenvolvido um sistema de medidas que utiliza pick-up de CDROM, retirada de um leitor comum, para medir a deflexão dos dispositivos. Esse tipo de arranjo é capaz de medir diferenças de nanômetros de deslocamento com um custo mínimo. Explorou-se a capacidade de controle de temperatura e leitura de deslocamento aplicando-se a técnica de modulação de temperatura nos estudos de eventos térmicos do PLGA. Observou-se que a modulação de temperatura é aplicável a esse tipo de medida e resultados muito semelhantes àqueles obtidos com técnicas convencionais são obtidos com uma quantidade muito menor de material. Como essas medidas foram realizadas utilizando sensores comerciais, realizamos a construção de matrizes de cantileveres no laboratório para demonstrar completo desenvolvimento desse tipo de plataforma de sensor. Empregando um polímero fotossensível relativamente novo para o desenvolvimento dessas matrizes, às utilizamos para caracterizações das propriedades mecânicas desse material. / The miniaturization of mechanical elements such as bridges or beams employing fabrication process previously used exclusively in microelectronics, resulted in the development of ubiquous physical sensors used today. The cantilever, or single supported beam is the most simple of these structures, but, when miniaturizated in the micrometer scale, the properties of the structure are highly dependent on events that takes place in its surface. Minimal superficial stresses like the ones generated by the adsorption of monolayers causes deflection of the structure in a scale that are easily measured by simple techniques. Moreover, the resonant frequency is highly dependent on relative mass changes of the device, making it a very sensitive microbalance. In this work, it was studied the application of microcantilevers as a platform for the study of materials properties, more specifically thermal analysis of polymeric material. When a very small quanitity of polymer is deposited in the surface of a silicon microcantilever, the structure will bend due to the mismatch of thermal expansion between the materials. Measuring the beam curvature in function of temperature enables the detection of thermal events suffered by the polymer. This effect was used to measure how the water absorption by the polymer affect the glass transition thermal event of the PLGA polymer. It was observed that this technique is faster if compared to traditional thermal chracterization techniques. To enable those characterizations, it was developed a measurement systems based on CDROM pick-up that can read the nanometer scale cantilever deflection with a minimum cost. The full capabilities of this system was then used to apply temperature modulation to the thermal studies of PLGA, we observed similar responses if compared to traditional approaches but with much less material use. Comercial sensors were used on these characterization, but, to present complet domain of cantilever sensor platform, we developed a fabrication process of polymeric cantilever array at the lab. These arrays were then used to extract mechanical information about the polymer used in its construction.

Lymph node metastasis is a critical prognostic factor for lung cancer. Effective therapy to control lymphatic metastasis may improve survival. The work described in this thesis focuses on the development of a microparticulate lymphatic targeting system, which can be applied as an adjuvant therapy in the control of lymphatic metastasis in lung cancer. The study shows that intrapleural administered colloidal particulates are predominantly taken up by regional lymphatic tissue in rat models including healthy rats, rats bearing orthotopic lung tumours and rats following pneumonectomy. The effect of particle size on lymphatic particle distribution was examined by intrapleural administration of 111In-aminopolystyrene beads. Approximately 2 µm is a suitable size for intrapleural lymphatic targeting. Biodegradable polylactide-co-glycolide (PLGA) microparticles containing the anticancer agent paclitaxel (PTX) were subsequently formulated in the desired size by spray drying. PLGA-PTX microspheres were incorporated into a biodegradable and biocompatible gelatin sponge matrix to form an implantable lymphatic targeted drug delivery system. The system was characterized in vitro and its lymphatic targeting ability was examined in vivo. Fluorescence labeled microspheres embedded within the sponge were selectively taken up by regional lymphatics as the sponge matrix disintegrated following intrapleural implantation. A pharmacokinetic study showed that the total PTX exposure in lymphatic tissue was dramatically higher than that achieved through intravenous administration. The peak plasma drug concentration, which governs systemic toxicity, was significantly reduced. The low but persistent detection of plasma PTX indicates that PTX was control released from the system after intrapleural implantation. In a therapeutic efficacy study performed in the H460 orthotopic lung cancer model, gelatin sponges containing PLGA-PTX microspheres were placed in the pleural cavity as an adjuvant treatment after surgical resection of the primary lung tumour. Trans-lymphatic chemotherapy resulted in a significantly lower incidence of lymphatic tumour recurrence (20%) compared to no treatment and placebo control animals (100%). PLGA-PTX microspheres were seen in regional lymphatic tissue over 4 weeks after the sponge placement. It is concluded that the trans-lymphatic targeting drug delivery system described in this thesis may improve the control of lymphatic metastasis in lung cancer.

Lymph node metastasis is a critical prognostic factor for lung cancer. Effective therapy to control lymphatic metastasis may improve survival. The work described in this thesis focuses on the development of a microparticulate lymphatic targeting system, which can be applied as an adjuvant therapy in the control of lymphatic metastasis in lung cancer. The study shows that intrapleural administered colloidal particulates are predominantly taken up by regional lymphatic tissue in rat models including healthy rats, rats bearing orthotopic lung tumours and rats following pneumonectomy. The effect of particle size on lymphatic particle distribution was examined by intrapleural administration of 111In-aminopolystyrene beads. Approximately 2 µm is a suitable size for intrapleural lymphatic targeting. Biodegradable polylactide-co-glycolide (PLGA) microparticles containing the anticancer agent paclitaxel (PTX) were subsequently formulated in the desired size by spray drying. PLGA-PTX microspheres were incorporated into a biodegradable and biocompatible gelatin sponge matrix to form an implantable lymphatic targeted drug delivery system. The system was characterized in vitro and its lymphatic targeting ability was examined in vivo. Fluorescence labeled microspheres embedded within the sponge were selectively taken up by regional lymphatics as the sponge matrix disintegrated following intrapleural implantation. A pharmacokinetic study showed that the total PTX exposure in lymphatic tissue was dramatically higher than that achieved through intravenous administration. The peak plasma drug concentration, which governs systemic toxicity, was significantly reduced. The low but persistent detection of plasma PTX indicates that PTX was control released from the system after intrapleural implantation. In a therapeutic efficacy study performed in the H460 orthotopic lung cancer model, gelatin sponges containing PLGA-PTX microspheres were placed in the pleural cavity as an adjuvant treatment after surgical resection of the primary lung tumour. Trans-lymphatic chemotherapy resulted in a significantly lower incidence of lymphatic tumour recurrence (20%) compared to no treatment and placebo control animals (100%). PLGA-PTX microspheres were seen in regional lymphatic tissue over 4 weeks after the sponge placement. It is concluded that the trans-lymphatic targeting drug delivery system described in this thesis may improve the control of lymphatic metastasis in lung cancer.

Malignant brain tumor is one of the most lethal forms of cancers. In the United States alone, approximately 20,500 new cases of primary malignant brain and central nervous system tumors are expected to be diagnosed in 2007 with 12,740 deaths estimated. Treatment of malignant brain tumor remains a major challenge despite recent advance in surgery and other adjuvant therapies, such as chemotherapy. The failure of potential effective chemotherapeutics for brain tumor treatment is usually not due to the lack of potency of the drug, but rather can be attributed to lack of therapeutic strategies capable of overcoming blood brain barrier for effective delivery of drug to the brain tumor. In this thesis, we developed a minimally invasive sustained release system for glioma therapy. The present study was initiated in an effort to incorporated Doxorubicin (DOX) loaded PLGA particle into an agarose gel, which can provide a continuous release of DOX locally to the tumor site. DOX, a toposiomearase II inhibitor, is not currently used clinically for brain tumor treatment because when delivered systemically it does not cross BBB. Our hydrogel particle system can overcome this shortcoming of DOX. The results from this study demonstrate that the DOX/PLGA particle gel system can maintain the bioactivity of DOX and sustained release DOX for at least 15 day in vitro. The result of in vivo study showed the DOX/PLGA particle gel treated group had significantly extend the medium survival of 9L glioma bearing rat from 21 days to 29 days. Therefore, the success experience of this local and sustained delivery device might benefit the development of future glioma therapy strategy.

The aim of this study was to develop drug delivery system based on poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles (NPs) to achieve personalized treatment of selected skin disorders, like photo-aging, psoriasis and atopic dermatitis. Dead Sea Water (DSW) and Retinyl Palmitate (RP) were used as active agents and they were loaded in PLGA NPs prepared either as spheres or capsules by o/w or w/o/w methods. MgCl2 and bovine serum albumin (BSA) served as model active compounds. The diameter of the NPs was found to be in the range of 280 - 550 nm. The entrapment efficiency (E.E.) was less than 1% for RP, DSW and MgCl2, and 41% for BSA. Loading of Cl- together with BSA doubled the E.E. value of Cl- . In situ release studies showed a burst in the first day and more than 85% of the chloride content was released within a week. When the macromolecule BSA was encapsulated, a much slower and triphasic release profile was observed which continued for up to 80 days. In vitro tests were performed using L929 fibroblast cells. Results of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) test revealed that none of the NPs were cytotoxic. Additionally, all particles were hemocompatible with hemolytic activity &lt / 1.5%. L929 fibroblast and Saos 2 human osteosarcoma cells were used to study the uptake of NPs by the cells. Particles accumulate near the nucleus. The characterization and cell viability tests, and drug release behavior indicate the suitability of these NPs for further testing to develop a patient specific skin diseases treatment approach.

Dexamethasone and dexamethasone 21-phosphate were loaded into NDGA-polymerized collagen fibers and release rate studies were performed to calculate their diffusion coefficients. Dexamethasone loaded fibers were placed in a PBS solution for specified time intervals (1, 3, 6, 7, 12, 24, 30, and 48 hours) after which the eluant was removed and analyzed by capillary zone electrophoresis (CZE). CZE is a tool that can be utilized for quantitative analysis of chemical compounds. This data was incorporated into mathematical models to determine the diffusion coefficient. The diffusion coefficient (D) for dexamethasone in NDGA-polymerized collagen fibers is D = 1.86 x 10⁻¹⁴ m²/s. Similarly, dexamethasone 21-phosphate loaded fibers were placed into a PBS solution and analyzed using CZE at these specified intervals (15, 30, 45, 60, and 75 minutes). Applying this data to the mathematical model provided a diffusion coefficient for dexamethasone 21-phosphate in NDGA-polymerized collagen fibers of D = 2.36 x 10⁻¹³ m²/s. In an effort to control drug delivery from these fibers a polylactic-co-glycolic acid (PLGA) coating was applied to the fibers. This coating helped sustain delivery of dexamethasone 21-phosphate for over a 100 day period. CZE experiments were again conducted in conjunction with another mathematical model to characterize release. A semi steady-state diffusion coefficient was estimated to be D = 4.59 x 10⁻¹⁴ m²/s.