RESUMEN
PURPOSE: We created implantable intraocular devices capable of constant and continuous rapamycin release on the scale of months to years. METHODS: Polycaprolactone (PCL) thin films were used to encapsulate rapamycin to create implantable and biodegradable intraocular devices. Different film devices were studied by modifying the size, thickness, and porosity of the PCL films. RESULTS: In vitro release of rapamycin was observed to be constant (zero-order) through 14 weeks of study. Release rates were tunable by altering PCL film porosity and thickness. In vivo release of rapamycin was observed out through 16 weeks with concentrations in the retina-choroid in the therapeutic range. Rapamycin concentration in the blood was below the lower limit of quantification. The drug remaining in the device was chemically stable in vitro and in vivo, and was sufficient to last for upwards of 2 years of total release. The mechanism of release is related to the dissolution kinetics of crystalline rapamycin. CONCLUSIONS: Microporous PCL thin film devices demonstrate good ocular compatibility and the ability to release rapamycin locally to the eye over the course of many weeks.
Asunto(s)
Implantes Absorbibles , Sistemas de Liberación de Medicamentos , Sirolimus/administración & dosificación , Uveítis/tratamiento farmacológico , Animales , Segmento Anterior del Ojo , Preparaciones de Acción Retardada/administración & dosificación , Modelos Animales de Enfermedad , Estudios de Seguimiento , Inmunosupresores/administración & dosificación , Conejos , Factores de TiempoRESUMEN
Chronic fibrosis caused by acute myocardial infarction (MI) leads to increased morbidity and mortality due to cardiac dysfunction. We have developed a therapeutic materials strategy that aims to mitigate myocardial fibrosis by utilizing injectable polymeric microstructures to mechanically alter the microenvironment. Polymeric microstructures were fabricated using photolithographic techniques and studied in a three-dimensional culture model of the fibrotic environment and by direct injection into the infarct zone of adult rats. Here, we show dose-dependent down-regulation of expression of genes associated with the mechanical fibrotic response in the presence of microstructures. Injection of this microstructured material into the infarct zone decreased levels of collagen and TGF-ß, increased elastin deposition and vascularization in the infarcted region, and improved functional outcomes after six weeks. Our results demonstrate the efficacy of these discrete anti-fibrotic microstructures and suggest a potential therapeutic materials approach for combatting pathologic fibrosis.
Asunto(s)
Materiales Biocompatibles/uso terapéutico , Metacrilatos/uso terapéutico , Infarto del Miocardio/patología , Infarto del Miocardio/terapia , Miocardio/patología , Polietilenglicoles/uso terapéutico , Células 3T3 , Animales , Materiales Biocompatibles/administración & dosificación , Colágeno/análisis , Femenino , Fibroblastos/citología , Fibrosis , Metacrilatos/administración & dosificación , Ratones , Microtecnología , Polietilenglicoles/administración & dosificación , Ratas Sprague-Dawley , Ingeniería de TejidosRESUMEN
OBJECTIVE: To evaluate the impact of the WellingTonne Challenge. DESIGN: Before-after study. SETTING: The National Action Agenda for the prevention and control of obesity in Australia identified community action and development as a key theme. The WellingTonne Challenge was a whole-of-community project designed to support a small rural community to lose weight and reduce their risk of chronic disease. PARTICIPANTS: Adult residents of the Wellington Local Government Area who were overweight or obese. RESULTS: The project successfully engaged the community with around 10% of the target group formally participating in the Challenge. Participants achieved a weight reduction of around 3 kg each, as well as positive changes in diet and physical activity. A total of 59% of those who signed up for the Challenge achieved an accumulated loss of 687 kg at the end of the 12-week program--less than the community goal of 1000 kg. CONCLUSION: The WellingTonne Challenge is a promising intervention. Wider implementation of this approach in other small rural communities might make a significant contribution to the national effort. The opportunity should be taken to undertake a more rigorous evaluation to determine whether this approach benefits communities in the longer term.