Polylactic acid and polylactic-co-glycolic acid are biocompatible and biodegradable polymers with wide utility for the design of controlled release systems for drugs. Regarding intraocular application, polymeric sustained-drug release systems are being studied to treat vitreoretinal diseases. Our work aimed to compare the influence of two implant manufacturing techniques, compression and hot molding, on the in vitro degradation of the polymeric matrices and on the release of dexamethasone acetate. The results showed that the manufacturing technique highly influences degradation and drug release processes. The compressed systems degraded faster and allowed one faster release of the drug.
1 May 2009 in Investigative Ophthalmology & Visual Science
The objective of this study was to evaluate the long-term safety and pharmacokinetic profile of a dexamethasone-loaded poly-epsilon-caprolactone (PCL) intravitreous implant. The PCL devices were prepared by compression and were inserted into the vitreous of pigmented rabbits. At different time points, vitreous samples were retrieved, and dexamethasone concentration was analyzed by high-performance liquid chromatography. The biodegradation of the implants was evaluated by scanning electron microscopy, and the dexamethasone remaining was evaluated at the end of follow-up. Clinical and histologic examinations were performed to evaluate the implant's tolerance. The PCL implant allows for a controlled and prolonged delivery of dexamethasone in rabbits eyes since it released the drug within the therapeutic range for at least 55 weeks. At 55 weeks approximately 79% of the drug was still present in the implant. Biodegradation study showed that PCL implants degradation is very slow. Clinical and histologic observations showed that the devices were very well tolerated in the rabbit eye. This study demonstrates the feasibility and tolerance of intravitreous PCL drug delivery systems, which can offer a wide range of applications for intraocular drug delivery because of their controlled and prolonged release over months or even years.
1 September 2010 in Brazilian Journal of Pharmaceutical Sciences
The treatment of diseases affecting the posterior segment of the eye is limited by the difficulty in transporting effective doses of drugs to the vitreous, retina, and choroid. Topically applied drugs are poorly absorbed due to the low permeability of the external ocular tissues and tearing. The blood-retina barrier limits drug diffusion from the systemic blood to the posterior segment, thus high doses of drug are needed to maintain therapeutic levels. In addition, systemic side effects are common. Intraocular injections could be an alternative, but the fast flowing blood supply in this region, associated with rapid clearance rates, causes drug concentration to quickly fall below therapeutic levels. To obtain therapeutic levels over longer time periods, polymeric sustained-drug release systems implanted within the vitreous are being studied for the treatment of vitreoretinal disorders. These systems are prepared using different kinds of biodegradable or non-biodegradable polymers. This review aims to demonstrate the main characteristics of these drug delivery implants and their potential for clinical application.