Polysulfone capillary fiber for intraocular drug delivery: in vitro and in vivo evaluations

Studies were conducted to investigate the usefulness of polysulfone capillary fiber (PCF) as a drug delivery device for intraocular applications. Carboxyfluorescein (CF) was used as a model drug to prepare PCF-dye devices for both in vitro and in vivo kinetic studies. For the in vitro study, PCF-CF devices were incubated in 0.1 M phosphate buffer, pH 7.4 at 37 degrees C, and CF release was quantified at various times up to 5 weeks. In vitro results indicated a bi-phasic, sustained-release profile of CF from the PCF device for over 30 days. PCF-CF devices released 5% and 10% of their initial CF contents by the first and second day following incubation, respectively. By 10 days after incubation, approximately 50% of the dye content was released from the PCF-CF devices. The rate of dye release decreased thereafter, such that 65% and 90% of CF was released by 17 and 28 days after incubation, respectively. In a subsequent study, the in vivo kinetics of the PCF-CF device were determined in the rabbit eye. PCF-dye devices were prepared with the following CF formulations: 1) microsphere-incorporated CF; 2) lyophilized liposome-encapsulated CF; or 3) micronized CF powder. A PCF-dye device was implanted in the vitreous cavity, and fluorophotometry from the retina to the anterior chamber was performed at various times up to 45 days to quantify fluorescein level. At the conclusion of the study, eyes were enucleated and examined for histopathology. The time-course study showed fluorescein level for up to 45 days in the vitreous. The midvitreous concentration-time profile indicated a CF t1/2 of 10 and 30 days for the PCF-CF powder and PCF-CF liposome preparation, respectively. In contrast, the PCF device prepared with microsphere-incorporated CF showed fluorescein level with a t1/2 of less than one week in the vitreous. Histological examination of the eyes implanted with PCF or PCF-dye device showed no sign of ocular toxicity. Collectively, these results indicated that the PCF device is biocompatible and may be useful for the extended release of drugs in the posterior segment of the eye.