Cyclodextrin–polysaccharide-based, in situ-gelled system for ocular antifungal delivery

Abstract

SummaryFluconazole was studied with two different hydrophilic cyclodextrins (hydroxypropyl-β-cyclodextrin (HPBCD) and sulfobutyl ether-β-cyclodextrin (SBECD)) for the formation of inclusion complexes. HPBCD and SBECD showed low cell cytotoxicity in human keratocytes as assessed by the label-free xCELLigence system for real-time monitoring. The fluconazole–HPBCD complex was incorporated into an ion-sensitive ophthalmic gel composed of the natural polysaccharides gellan gum and κ-carrageenan. This system showed good bioadhesive properties and effective control of fluconazole release.

In vitro and in vivo ocular safety and eye surface permanence determination by direct and Magnetic Resonance Imaging of ion-sensitive hydrogels based on gellan gum and kappa-carrageenan

“…This result is in agreement with the obtained result by direct examination using Trypan Blue and indicates that part of the gel removed from the surface of the eye builds up under the eyelids. Previous studies developed using similar in situ gels containing the antifungal fluconazole [30] have shown the capacity of this systems to control the release of the drug by a mechanism diffusion-mediated at least for 3 h. Therefore the hydrogel that remains under the eyelids and in the corneal surface would act as a drug reservoir.…”

“…Hen's Egg Test Chorion allantoic Membrane (Het-Cam) [29] was used to study the acute ocular irritability using similar methodology as described in the previous work [30]. A volume of 0.3 ml of 1% of polysaccharides dispersions, ion sensitive hydrogel or control solutions (0.1 N sodium hydroxide was used as a positive control and 0.9% sodium chloride as a negative control) were tested.…”

Biopharmaceutical Assessment of Dexamethasone Acetate-Based Hydrogels Combining Hydroxypropyl Cyclodextrins and Polysaccharides for Ocular Delivery

“…One can note that in the present study, HPγCD had a much less pronounced effect than HPβCD, showing a cell viability higher than 65%, against lower than 30% for HPβCD (p-value < 0.001 at 30 min). Moreover, the cytotoxicity of HPβCD is enhanced with increasing exposure time [ 34 ]. These differences may be attributed to the higher propensity of the βCD derivative to solubilize cholesterol from membranes compared to γCD [ 33 ].…”

Preparation of alginate–chitosan–cyclodextrin micro- and nanoparticles loaded with anti-tuberculosis compounds

“…The addition of cyclodextrins to the microparticles results in (i) an increase of stability, solubility, and bioavailability of the active compounds in the complex; this has been proved for the delivery of antifungal triazole and imidazole compounds [14–15]; and (ii) an increased penetration of cell walls. There have been numerous examples in the literature about this [2,15–16].…”