Chitosan Nanoparticles as New Ocular Drug Delivery Systems: In Vitro Stability, in Vivo Fate, and Cellular Toxicity

Abstract

Purpose. To assess the potential of chitosan (CS) nanoparticles for ocular drug delivery by investigating their interaction with the ocular mucosa in vivo and also their toxicity in conjunctival cell cultures. Methods. Fluorescent (CS-fl) nanoparticles were prepared by ionotropic gelation. The stability of the particles in the presence of lysozyme was investigated by determining the size and their interaction with mucin, by measuring the viscosity of the mucin dispersion. The in vivo interaction of CS-fl nanoparticles with the rabbit cornea and conjunctiva was analyzed by spectrofluorimetry and confocal microscopy. Their potential toxicity was assessed in a human conjunctival cell line by determining cell survival and viability. Results. CS-fl nanoparticles were stable upon incubation with lysozyme and did not affect the viscosity of a mucin dispersion. In vivo studies showed that the amounts of CS-fl in cornea and conjunctiva were significantly higher for CS-fl nanoparticles than for a control CS-fl solution, these amounts being fairly constant for up to 24 h. Confocal studies suggest that nanoparticles penetrate into the corneal and conjunctival epithelia. Cell survival at 24 h after incubation with CS nanoparticles was high and the viability of the recovered cells was near 100%. Conclusions. CS nanoparticles are promising vehicles for ocular drug delivery.

Methods to determine the interactions of micro- and nanoparticles with mucus

“…They suggested that chitosan as well as Carbopol polymers have a high affinity to the mucin particles [22]. Furthermore, this method can be used to assess the stability of nanoparticles in biological fluids containing various proteins and enzymes [23].…”

Development of drug-loaded chitosan–vanillin nanoparticles and its cytotoxicity against HT-29 cells

“…HT-29 cells in logarithmic growth phase were cultured in a confocal dish for the cellular uptake of fluorescein-loaded DOI: 10.3109/10717544.2014.900590 chitosan nanoparticles (Campos et al, 2004). After 24-h incubation, fresh RPMI1640 medium containing fluoresceinloaded chitosan nanoparticles at different concentrations (0.0625 and 2 mg/mL) was added into each dish.…”

Ocular Sustained Release Nanoparticles Containing Stereoisomeric Dipeptide Prodrugs of Acyclovir

“…However, the major limitation with polymeric nanocarriers is short residence in the precorneal area. 13 In this article, we report alternative strategies for increasing the overall therapeutic efficacy of the ACV-prodrugs after topical administration. The stereoisomeric peptide prodrugs of ACV (LV-LV-ACV, LV-DV-ACV, DV-LV-ACV, and DV-DV-ACV) were evaluated for bioreversion in corneal cell and tissue homogenates.…”