Abstract
Purpose: :
Cytotoxic drugs are potent candidate for prevention of posterior capsular opacification (PCO) but toxicity to the intra ocular structures remain a major concern. The purpose of the present study was to prepare and characterize doxorubicin loaded MePEG-PCL nano particle and evaluate its effect on PCO formation. Aqueous availability of doxorubicin and toxicity to intra ocular structures following nanoparticle mediated delivery of the drug.
Methods: :
PEG-PCL nanodoxorubicin was prepared and characterized for surface morphology, particle size, zeta potential and distribution of drug within the nanoparticle. Cellular effects of nano doxorubicin on cultured lens epithelial cells were compared with free drug. Lensectomy was performed in one eye of rabbits followed by subconjunctival injection of doxorubicin nanoparticles. The availability of doxorubicin in aqueous was determined by HPLC. PCO formation was evaluated by slit lamp biomicroscopy, Miyake apple posterior view and histopathology. The toxicity on intraocular structures was evaluated by tonometry, specular microscopy, and histopathology
Results: :
TEM and AFM showed smooth surface of the nanoparticles and confocal microscopy showed presence of doxorubicin within the particles. Particle size and zeta potential were 92.85 nm and 36.5 mV respectively as determined by DLS. Time of cellular entry of doxorubicin nanoparticles did not differ from the free drug but in former case drug retention within the cell prolonged and cytotoxic effect on LEC increased significantly. Sustained release of doxorubicin was detectable in the aqueous humor. There was significant decrease in PCO in the treated eye, compared to untreated operated eye and no toxicity was observed on intraocular structures following use of nanodoxorubicin
Conclusions: :
The use of MePEG-PCL doxorubicin by subconjunctival route can prevent PCO without inciting ocular toxicity.
Keywords: cataract • apoptosis/cell death • cell survival