Noriyuki Kunou

Controlled intraocular delivery of ganciclovir with use of biodegradable scleral implant in rabbits

Abstract We evaluated biodegradable scleral implants as a controlled intraocular delivery system of ganciclovir (GCV) for the treatment of cytomegalovirus retinitis in rabbits. The scleral implants (weight, 8.5 mg; length, 5 mm) were made of poly( dl -lactide) (PLA) or poly( dl -lactide-co-glycolide) (PLGA) and contained various amounts of GCV. The in vitro release studies demonstrated a triphasic release pattern. The 10% GCV-loaded scleral implant made from PLA with a molecular weight of 130 000 released GCV for 6 months. The in vivo release and biodegradation were studied using the 25% GCV-loaded implant made from PLGA( 75 25 ) with a molecular weight of 121 000 in pigmented rabbits. The GCV concentration in the range of ED 90 for human CMV was maintained in the vitreous for over 3 months and in the retina/choroid for over 5 months. The GCV concentration was greater in the retina/choroid than in the vitreous throughout the study. The scleral implants showed two phases of biodegradation: lagtime and erosion. In the erosion phase, the weight of PLGA dropped remarkably. All the scleral implants were separated into two pieces at the site of scleral penetration and displaced into the vitreous 10 weeks after implantation. The fragments disappeared from the vitreous and the subconjunctival space 5 months after implantation. Our findings suggest that the biodegradable scleral implant may be a promising device for the intraocular drug delivery of GCV.

Biodegradable scleral implant for intravitreal controlled release of ganciclovir

Abstract · Background: The aims of this study were to develop biodegradable scleral implants that could overcome previously reported disadvantages such as an adverse burst in the late phase of release and to investigate the release profile of modified scleral implants in vitro and in vivo. · Methods:The modified scleral implants (weight 8.5 mg, length 5 mm) were made of mixtures of poly(dl-lactide) (PLA) with different molecular weights and contained 25 weight % of ganciclovir (GCV). The release of GCV was evaluated in vitro by spectrophotometry. Intravitreal GCV concentrations in vivo were measured by high- performance liquid chromatography following plug implantation in pigmented rabbits. The biocompatibility of the device was determined by indirect ophthalmoscopy and light microscopy. · Results:The in vitro release studies showed stable, long-term sustained and slow release. The in vivo release studies showed that the implants had long-term release in the diffusional phase of the triphasic release pattern and only a minor adverse burst of GCV in the late phase. No significant retinal toxicity was observed by histologic examination.  · Conclusion: Our findings showed that this newly modified scleral implant may provide suitable intravitreal drug delivery for treatment of cytomegalovirus retinitis.

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.

Suppression of laser-induced choroidal neovascularization by posterior sub-tenon administration of triamcinolone acetonide.

Purpose: To evaluate the inhibitory effect of triamcinolone acetonide (TA) on choroidal neovascularization (CNV) by posterior sub-Tenon administration using a laser-induced CNV model in the rat. Methods: Experimental CNV was induced by laser photocoagulation in Brown–Norway male rats. Experimental eyes received posterior sub-Tenon administration of either 2 mg (n = 10) or 0.5 mg (n = 8) of TA. Control eyes (n = 10) received posterior sub-Tenon administration of isotonic sodium chloride solution. Two weeks after treatment, CNV was evaluated by fluorescein angiography and histopathological examination. Concentrations of TA in the vitreous, retina, and choroid were determined by high-performance liquid chromatography at 3 and 7 days after posterior sub-Tenon administration. Results: The eyes treated with 2 mg of TA showed statistically significant inhibition of fluorescein leakage by fluorescein angiography, as compared with control eyes and eyes treated with 0.5 mg of TA (P < 0.01). The thickness of CNV membranes in eyes treated with 2 mg of TA also decreased statistically significantly, as compared with control eyes (P < 0.01). TA was detected in the vitreous, retina, and choroid 3 days after administration and in the choroid 7 days after administration. Conclusions: Posterior sub-Tenon administration of TA may be useful to treat CNV.