for ARN usually involves intravenous or intravitreal administration of acycloguanosine (acyclovir). Intravitreal administration of acyclovir has demonstrated to be more effective than the intravenous administration of the drug and have fewer side effects. Although the intravitreal therapy is effective, the relatively high dose that is required has untoward side effects. Conte et al. (1997) developed a controlled release formulation from different PLA and PLGA polymers loaded with acyclovir using the spray drying technique. In vivo evaluation was studied by injecting 0.5 mg of microparticles (25 mm diameter) from D,L-PLA (28,000 Da) into rabbit eyes. Drug levels were detected in the vitreous for 14 days after microparticles administration. Chowdhury and Mitra (2000) have described guanosine-loaded PLGA (75,000– 100,000 Da) microspheres developed for a drug release of 1 week after intravitreal injection of the particles. Martinez-Sancho et al. (2003a) prepared PLGA microspheres loaded with acyclovir for intraocular injection. The authors employed several additives (aqueous soluble substances and oils) to optimize the release rate of the active substance from the particles. Microspheres were prepared by the O/W emulsion technique. The dose of microparticles needed for therapeutic effect was significantly reduced when adding gelatin in the external phase of the emulsion (Martinez et al. 2003b).

10.9.7  Cytomegalovirus (CMV) Retinitis

CMV retinitis occurs in immunodeficiency patients. The CMV infection is progressive and can result in blindness from RD associated with retinal necrosis (Jab et al. 1989; Henry et al. 1987). Although intravitreal ganciclovir injections provide effective intraocular drug concentrations, frequent injections are required to maintain therapeutic drug levels. Veloso et al. (1997) tested the antiviral effect of ganciclovir released from PLGA microspheres in rabbit eyes inoculated with the human cytomegalovirus (HCMV). Ten milligram injection of 300–500 mm ganciclovir-loaded microspheres prepared from PLGA 50:50 (inherent viscosity 0.39 dl/g) containing 864.04 mg of the drug controlled the progression of fundus disease in the HCMV-inoculated rabbit eyes.

10.9.8  Choroidal Neovascularization

Poly(d,L lactide-co-glycolide) glucose microspheres loaded with a kinase inhibitor PKC412 were injected in a porcine model of CNV (Saishin et al. 2003). Laser photo-coagulation was used to rupture Bruch’s membrane in eight locations. After that, periocular injection of microspheres suspended in 1 ml of an aqueous vehicle was performed in the animals. Microspheres containing 25 or 50% of PCK412 were compared to blank microspheres. After 10 days of injection the integrated areas of CNV at Bruch’s membrane rupture sites measured by image analysis resulted lower after injection of PCK412 microspheres. Twenty days after periocular injection PCK412 levels were detected for the PCK412 loaded microparticles.

10.9.9  Diseases Affecting the Optic Nerve

Neuroprotection has been proposed as a therapeutic option for the treatment of glaucoma (Jiang et al. 2007). This treatment focuses on promoting the survival of retinal ganglion cells (RGC). RGC survival can be achieved by neurotrophins. PLGA50:50 (Mw 25,000 Da) microspheres containing glial-cell-line-derived neurotrophic factor (GDNF) were assayed in mice. Checa et al. (2011) have developed “combo microparticles” loaded with antioxidants and neurotrophic factors to increase the survival of RGC.

10.9.10  Intraocular Inflammation and Infection

After Cataract Surgery

Ocular inflammation and infection after cataract surgery can be prevented with a combination of steroids and antibiotic agents delivered from microparticles. Paganelly et al. (2009) injected periocularly 2 mg of PLGA (50:50) microspheres (mean size 1.07 ± 0.35 mm) loaded with ciprofloxacin (0.99 mg) with 25 mg of TA in humans. The combined treatment was compared with topical administration of prednisolone (1%) and ciprofloxacin (3%) eye drops administered during 4 weeks. These patients received an injection of blank microspheres. Both treatments were evaluated in terms of efficacy (anterior chamber cell and flare, conjunctival erythema, ciliary flush, or symptoms of ocular inflammation) and safety (intraocular pressure, biomicroscopy, and ophthalmoscopic findings). The authors stated the same therapeutic response and ocular tolerance with both pharmacological therapies after age-related cataract surgery.

10.9.11  Microparticles in Retinal Repair

Failure of the adult mammalian retina to regenerate can be partly attributed to the barrier formed after degeneration that separates a subretinal graft from integrating into the host retina. This mentioned barrier is formed by inhibitory extracellular matrix (ECM) and cell adhesion molecules, such as CD44 and neurocan.

Matrix metalloproteinase 2 (MMP2) can promote host-donor integration by degrading these molecules. In order to enhance cellular integration and promote retinal repopulation, a retinal combination of PLGA microspheres loaded with MMP2 and retinal progenitor cells (RPCs) have been assayed (Yao et al. 2011). In this study, PLGA microspheres loaded with MMP2 and RPCs were co-transplanted to the subretinal space of adult retinal degenerative Rho−/− mice. High porous microspheres loaded with MMP2 were prepared by a double emulsion technique.