A new vitreal drug delivery system using an implantable biodegradable polymeric device.

PURPOSE: The authors evaluated the feasibility of using an implantable biodegradable polymeric device to deliver drugs into the vitreous humor. METHODS: Two types of devices were prepared by compression-molding polymers of poly(DL-lactic acid) of two different molecular weights. The molecular weights of the poly(DL-lactic acid) used were 5,600 (device-1) and 9,100 (device-2). Sodium fluorescein (NaF) served as a hydrophilic drug marker. The release of the dye from the devices was studied in vitro. The intravitreal kinetics of NaF was evaluated in rabbits in vivo by fluorophotometry. The eyes were evaluated electrophysiologically and histologically to determine if there were toxic effects. RESULTS: Device-1 and device-2 released NaF for more than 25 and 45 days, respectively, in vitro. Detectable concentrations of NaF were present in the vitreous up to 17 days (device-1) and 28 days (device-2). Both types of devices were well tolerated, with no noted toxic effects. CONCLUSIONS: These results suggested that this device may be a potentially effective system to deliver drugs in the vitreous.

Scleral plug of biodegradable polymers for controlled drug release in the vitreous.

We designed a new device, a scleral plug, that releases drugs into the vitreous after being implanted and fixed at the pars plana. Use of the plug for provision of doxorubicin hydrochloride was evaluated in rabbits. The scleral plug (8.5 mg) was made of poly(lactic-glycolic acid) (molecular weight, 40,000 daltons) containing 1% doxorubicin. Vitreous concentrations of doxorubicin were measured after the implantation. In vitro studies showed that the plug released 26% of the drug during 4 weeks. In vivo studies demonstrated that the concentration in the vitreous humor was maintained at a therapeutic range for longer than 4 weeks. No substantial toxic reactions were observed by electroretinographic and histopathologic evaluations. Our findings suggested that a scleral plug made of biodegradable polymers is a promising device for a controlled drug-release system in the vitreous.

Implantable biodegradable polymeric device in the treatment of experimental proliferative vitreoretinopathy.

We investigated the use of a scleral plug of biodegradable polymer implanted at the pars plana to create a controlled drug-delivery system in the vitreous. We evaluated the efficacy of a plug containing doxorubicin hydrochloride to treat experimental proliferative vitreoretinopathy (PVR) in pigmented rabbits. An implantable device on the sclera, which imitates a scleral plug, containing 1% doxorubicin, was prepared with poly(lactic acid) (molecular weight, 20,000). The release of doxorubicin in phosphate-buffered saline was evaluated by spectro-photometry. After pars plana vitrectomy and plug implantation, concentrations of doxorubicin in the vitreous humor of the rabbits were measured by high performance liquid chromatography. The release profiles were evaluated during 5 weeks in vitro and 4 weeks in vivo. Cultured homologous fibroblasts were injected into the vitreous space to induce experimental PVR after gas compression of the vitreous. The scleral plugs were implanted at the pars plana in treatment animals (n = 11). Control rabbits (n = 11) were followed up without implantation after PVR induction. All eyes of the control group developed tractional retinal detachment at day 28, while the incidence of retinal detachment was decreased to 64% in the treated eyes. (P = 0.002). The implantation of the scleral plug effectively inhibited intravitreous proliferation of fibroblasts. This study demonstrated that the scleral plug of biodegradable polymers may have potential as a treatment modality for PVR.

Biodegradable polymeric device for sustained intravitreal release of ganciclovir in rabbits.

PURPOSE: A scleral plug made of biodegradable polymer implanted at the pars plana was evaluated to determine its ability to control the intravitreal release of ganciclovir. METHODS: Scleral plugs containing 25% ganciclovir were prepared with poly(lactic-glycolic acid) (molecular weight, 121 kDa). The release of ganciclovir was evaluated in vitro by spectrophotometry. In vivo intravitreal ganciclovir concentrations were measured by high performance liquid chromatography following plug implantation in pigmented rabbits. The biocompatibility of the device was determined by indirect ophthalmoscopy, electroretinography, and light and electron microscopy. RESULTS: The in vitro study showed that the plug released ganciclovir throughout a 10-week period. The in vivo study demonstrated that the plugs maintained the drug concentration in the vitreous in a therapeutic range adequate to treat cytomegalovirus (CMV) retinitis for 12 weeks. No significant retinal toxicity was observed. CONCLUSIONS: This study demonstrated that this drug delivery system can potentially be useful to treat CMV retinitis.

Equator ring efficacy in maintaining capsular bag integrity and transparency after cataract removal in monkey eyes.

BACKGROUND: The purpose of the study was to evaluate the efficacy of the equator ring in maintaining capsular bag integrity at the equator and transparency of the posterior capsule after cataract surgery. using cynomolgus monkeys. METHODS: After lens removal using an infusion-aspiration method, a flexible silicone ring with a groove on its inner surface was inserted in the bag through a window made by continuous circular capsulorhexis in six eyes. Of these, four monkey eyes underwent posterior chamber intraocular lens (IOL) implantation and two monkey eyes did not receive IOLs. Lensectomy without ring insertion was performed as a control in the six fellow eyes. Of these, four eyes received an IOL and two did not. The eyes were followed for an average of 5.9 +/- 1.1 months before enucleation. The effects were evaluated by stereo and light microscopy. RESULTS: The ring effectively maintained the circular contour of the capsular bag (ratio of the short and long axes, 0.97 +/- 0.01) and posterior capsule transparency (P = 0.017). CONCLUSIONS: This study demonstrated that the equator ring is a promising device for maintaining capsular bag integrity and minimizing posterior capsule opacification after cataract surgery.