Doxorubicin-loaded MePEG-PCL nanoparticles for prevention of posterior capsular opacification.

AIMS: Cytotoxic drugs are considered as potent candidates for the prevention of posterior capsular opacification (PCO), but the toxicity incited to healthy intraocular structures is a major concern. In this study, the authors evaluated the effect of PEG methyl ether-block-poly(ε-caprolactone) (MePEG-PCL) doxorubicin (DOX)-loaded nanoparticles (NPs) for prevention of PCO and their influence on intraocular tissues. METHODS: MePEG-PCL DOX NPs were prepared and characterized. The cytotoxic effect of DOX NPs on lens epithelial cells was compared with free drug. Its effect on PCO prevention following single subconjunctival delivery to lensectomized rabbits was assessed. Toxicity to intraocular structures was evaluated by specular microscopy, electroretinography and histopathology. The availability of DOX in aqueous humor was determined by HPLC. RESULTS: The cytotoxic effect of DOX NPs was higher compared with free DOX due to prolonged retention within the cells. A significant reduction in degree of PCO was observed in DOX NP-treated eyes compared with untreated controls. There was no significant change in the density and morphology of corneal endothelial cells or the histology of intraocular structures. Electroretinographs of treated eyes did not change compared with the pretreatment values. DOX could be detected by HPLC in the aqueous humor up to 48 h following single subconjunctival injection. CONCLUSION: The authors conclude that DOX-loaded MePEG-PCL NPs show promise as a new approach to selectively kill highly proliferative lens epithelial cells in vivo following cataract surgery, while sparing normal tissue.

Modulation of matrix metalloproteinase activity by EDTA prevents posterior capsular opacification.

PURPOSE: To evaluate the effect of ethylenediaminetetraacetic acid (EDTA) on posterior capsular opacification (PCO) of rabbits and to assess its effect on intraocular tissues. METHODS: Modulation of matrix metalloproteinase (MMP) activity in the aqueous following cataract surgery in rabbits and its prevention by different doses of EDTA was determined by zymography. For evaluation of PCO, lensectomized rabbits were intracamerally injected with single dose of either 5 mg EDTA or normal saline. After one month, the degree of PCO was determined by slitlamp biomicroscopy, Miyake-Apple view, and histology of the lens capsule. The effect of EDTA on intra ocular pressure (IOP), corneal endothelial cells, and the retina was evaluated by tonometry, specular microscopy and scanning electron microscopy, and electroretinography. The concentration of EDTA in the aqueous was determined by high performance liquid chromatography (HPLC) at different time points. RESULTS: The MMP activity was significantly increased in the aqueous of the operated eyes, and EDTA reduced the degree of increase in a dose-dependent manner. EDTA treatment significantly reduced the degree of PCO (p<0.05). Histopathology of the lens capsule showed a reduction in the number of proliferating and migrating cells as well as MMP2 expression in the EDTA-treated eyes. EDTA treatment did not change the IOP; density, morphology and ultrastructure of the corneal endothelial cells; and electroretinography (ERG). EDTA was detectable in the aqueous humor up to 72 h following a single intracameral injection. CONCLUSIONS: EDTA reduces the degree of PCO by suppressing the MMP activity and it is not toxic to intra ocular structures at the concentration used.

Comparison of design of intraocular lens versus the material for PCO prevention.

AIM: To evaluate the influence of different intraocular lens(IOL) designs made of PMMA on posterior capsular opacification(PCO) and compare with foldable designs. METHODS: Phacoemulsification and IOL implantation was done in one eye of 24 New Zealand White rabbits, with IOL of two different designs (Square edged or round edge) and two different materials(PMMA or HEMA). After three months, the animals were sacrificed and enucleated. Evaluation of PCO included posterior view, migration of anterior capsular epithelial cells to the posterior capsule following epithelial-mesenchymal transition were assessed by staining the histological sections of posterior capsule by hematoxylin-eosin(HE) and Periodic acid- Schiff (PAS). The IOLs were extracted and stained with HE to evaluate the presence of adherent cells on the lens surface. RESULTS: PCO was highest with round edged rigid lens. There was no significant difference in the PCO between the square edged PMMA and square edged foldable lens. CONCLUSION: It is the design of the IOL not the material that offers protection on PCO formation.