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.
Highlights
Corneal diseases, second to cataracts, represent a major cause of blindness, where most regions of the eye are vulnerable to fungal infections [1,2,3]
The first line to treat fungal keratitis was through the topical administration of amphotericin B, patients suffered from poor vision as a result of this
Silica nanoparticles were synthesized via the crosslinking between tetraethyl ortho silicate (TEOS) and chitosan HCl, representing the silica and nitrogen sources, respectively
Summary
Second to cataracts, represent a major cause of blindness, where most regions of the eye are vulnerable to fungal infections [1,2,3]. Silica nanoparticles represent one of the recently introduced nanoplatforms in the drug delivery field [18,19,20] They offer several advantages, such as the ease of fabrication, better drug encapsulation, enhanced drug solubility as well as controlling drug release [21]. Cyclodextrins were recognized as effective pharmaceutical excipients [44] Their hollow torus-shaped molecules comprising a lipophilic cavity and hydrophilic outer surface enable them to solubilize hydrophobic drugs through an inclusion complexation process [45]. Both HβCD and MβCD are available as pharmaceutical excipients in marketed eye drops, i.e., Indocollirio (Bausch & Lomb, France) and Clorocil (Oftalder, Poland), respectively Another added value for the use of cyclodextrins is their ability to protect nanoparticles during the freeze drying process via acting as cryoprotectants. The solidification of the silica/chitosan nanoparticle dispersion by freeze drying using cyclodextrins as cryoprotectants is addressed in the present study for the first time
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call