DEVELOPMENT AND CHARACTERIZATION OF TOPICAL OPHTHALMIC FORMULATIONS CONTAINING LUTEIN-LOADED MUCOADHESIVE NANOPARTICLES

Objective: To develop and characterize a topical ophthalmic formulation containing chitosan-dextran sulfate nano particles (CDNs) for enhanced ocular bioavailability and stability of lutein.Methods: Lutein-loaded CDNs (LCDNs) were prepared by polyelectrolyte complexation employing oppositely charged polymers, chitosan and dextran sulfate. Effects of the polymer mass ratios, the total amount of polymers, and the amount of EDC and PEG400 on their physicochemical properties as well as the drug release profiles were investigated. The physicochemical stability of LCDNs dispersed in various ophthalmic vehicles and the accompanying microbial contamination were also evaluated.Results: LCDNs possessed a mean size of ~400 nm with a positive surface charge of+30 mV and entrapment efficiency up to 75%. Dissolution profiles followed a Higuchi's square root model, indicating a diffusional release mechanism. LCDNs dispersed in Feldman ophthalmic buffer showed good physical stability with no microbial contamination. The chemical stability of lutein was significantly improved in LCDNs and further improved by the addition of antioxidant in the ophthalmic vehicle.Conclusion: The ophthalmic formulation containing LCDNs, developed in this work, has characteristics suitable for application in ocular surface drug delivery systems.Keywords: Chitosan, dextran sulfate, Nanoparticles, Ophthalmic vehicle, Lutein

PENETRATION OF HYDROPHILIC SULFORHODAMINE B ACROSS THE PORCINE CORNEA EX-VIVO

Objective: Sulforhodamine B (SRB) is a hydrophilic tracer whose fluorescence is unaffected by pH unlike that of carboxyfluorescein. Therefore, SRB may serve as a better tracer when there are significant changes in pH. Thus, in this study, the suitability of SRB to assess the barrier properties of the cellular layers of the cornea was examined using a custom-built confocal scanning micro-fluorometer (CSMF). Methods: The dye solution (0.1% SRB) was prepared in PBS-Ca2+and three experiments were performed ex vivo using freshly isolated porcine eyes. First, we investigated the penetration of SRB across the endothelium by injection of the dye into the anterior chamber. Next, we measured the penetration of SRB across the epithelium after exposing the ocular surface to the dye. Finally, we examined the penetration after exposure to the dye with detergent (Tween 20) and exposure to the dye concomitant with microneedle injuries. The dye concentration profiles across the cornea were measured using CSMF.Results: SRB penetrated the corneal endothelium readily into the stroma following injection into the anterior chamber in a time-dependent manner. Despite accumulation in the stroma, SRB did not partition into the epithelium. In agreement with these findings, the dye did not cross the epithelium after topical administration. Co-administration with Tween 20 and injury to the epithelium with microneedles, however, led to penetration of the dye into the stroma.Conclusions: SRB is a hydrophilic dye that can be used as an alternative fluorescent tracer to assess the barrier function of the cellular layers of the cornea