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J Ocul Pharmacol Ther. 2013 Mar;29(2):208-15. doi: 10.1089/jop.2012.0184. Epub 2013 Feb 21.

Sustained release of 5-fluorouracil from chitosan nanoparticles surface modified intra ocular lens to prevent posterior capsule opacification: an in vitro and in vivo study.

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  • 1Department of Ophthalmology of Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.

Abstract

PURPOSE:

The study aimed to prepare a new type intra ocular lens (IOL), in which 5-Fu, as an antimetabolite drug, could be sustained released to prevent posterior capsule opacification (PCO), and evaluate its efficacy and safety in vitro and in vivo.

METHODS:

5-fluorouracil chitosan nanoparticles (5-Fu-CSNP) were prepared by template polymerization and selected by a cell counting kit (CCK-8). The 5-Fu-CSNPs that inhibit Human Lens Epithelial Cells (HLECs) proliferation most efficiently were chosen for further analysis. We then investigated cell death type in vitro by flow cytometry and fluorescent probe. IOLs were surface modified by 5-Fu-CSNP after being activated by a low energy fluorine ion beam, and then were implanted into rabbits' eyes after transparent lens enucleation to evaluate the efficacy of preventing PCO and safety in anterior chamber. Transparency and haze of the 5-Fu-CSNP-surface-modified intraocular lens (Nano-5-Fu-IOL) were detected by a haze meter. Drug release of the Nano-5-Fu-IOL was measured by UV spectrophotometry.

RESULTS:

The CCK results showed that the half inhibition dose (ID50) of the HLECs in 5-Fu-CSNP group and in 5-Fu solution group was 0.2 μg/mL and 1 μg/mL, respectively. The transparency of the 5-Fu-CSNP modified IOL was observed to have no significant difference with the blank control. The IOLs can continuously release 5-Fu in 4 days in vitro. In vivo, 5-Fu-CSNP IOL group had little aqueous flare 3 days after the surgery, and lighter PCO 4 weeks after the surgery than the blank control group. The results of the light microscope and electron microscope further confirmed the above results in vivo.

CONCLUSIONS:

The new IOL modified by 5-Fu-CSNP could be prepared and have a sustained release of 5-Fu to prevent PCO by promoting HLEC apoptosis. The drug-loaded CSNP could reduce the anterior chamber toxicity of 5-Fu markedly, which was probably due to the occurrence of endoplasmic reticulum stress and induction of apoptosis.

PMID:
23428176
[PubMed - indexed for MEDLINE]
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