Cyclodextrin Stabilized Freeze-Dried Silica/Chitosan Nanoparticles for Improved Terconazole Ocular Bioavailability

Abstract

This research assesses the beneficial effects of loading terconazole, a poorly water-soluble antifungal drug in silica/chitosan nanoparticles (SCNs) for ocular delivery. Nanoparticles were fabricated by the simple mixing of tetraethyl ortho silicate (TEOS) and chitosan HCl as sources of silica and nitrogen, respectively, along with alcoholic drug solution in different concentrations. Freeze-dried nanoparticles were fabricated using cyclodextrins as cryoprotectants. SCNs were assessed for their particle size, PDI, yield, drug loading and in vitro release studies. A 23.31 full factorial experimental design was constructed to optimize the prepared SCNs. DSC, XRD, FTIR, in addition to morphological scanning were performed on the optimized nanoparticles followed by an investigation of their pharmacokinetic parameters after topical ocular application in male Albino rabbits. The results reveal that increasing the water content in the preparations causes an increase in the yield and size of nanoparticles. On the other hand, increasing the TEOS content in the preparations, caused a decrease in the yield and size of nanoparticles. The optimized formulation possessed excellent mucoadhesive properties with potential safety concerning the investigated rabbit eye tissues. The higher Cmax and AUC0–24 values coupled with a longer tmax value compared to the drug suspension in the rabbits’ eyes indicated the potential of SCNs as promising ocular carriers for poorly water-soluble drugs, such as terconazole.

Solubility enhancement of some poorly soluble drugs by solid dispersion using Ziziphus spina-christi gum polymer

“…The modification by freeze-drying showed the highest percentage yield. These results were similar to those obtained by Zaghloul et al in their study on Silica/Chitosan for improving the solubility of Terconazole ( Zaghloul et al, 2022 ).

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PLGA-modified Syloid®-based microparticles for the ocular delivery of terconazole: in-vitro and in-vivo investigations

“…It was observed that upon increasing Syloid ® amount in the drug: Syloid ® weight ratio from 1:1 and 1:2 to 1:4 and 1:6, there was a significant decrease ( p < 0.05 ) in DL%. This is in logical accordance with the increase in the total solids relative to a constant drug amount (decrease mass ratio of drug to microparticles) (Zaghloul et al., 2022 ).…”

“…Unfortunately, its poor aqueous solubility limits its ocular application. The literature sheds the light on several studies investigating the use of terconazole for ocular delivery applying various formulation techniques, including the fabrication of silica/chitosan nanoparticles (Zaghloul et al., 2022 ) and cationic polymeric nanoparticles (Mohsen, 2022 ).…”

The Role of Cryoprotective Agents in Liposome Stabilization and Preservation

“…When a cryoprotectant reaches a certain temperature, it vitrifies, creating a glassy matrix that can shield nanoparticles from the ice’s mechanical stress. The majority of research on cryoprotectants show their inclusion improves liposome stability [ 149 ]. In essence, the efficacy of freeze-drying to maintain liposome stability in an aqueous state depends on a complex relationship between protectants and bilayer composition, not merely the kind and position (the inner core or bulk water) of the protectant or the determination of process parameters.…”