Gholamabbas Chehardoli - Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Zahra Ganjirad - Student Research Committee, Hamedan University of medical sciences, Hamedan, Iran.
Asrin Bahmani - Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Background and Objective: Over the years, many studies have been conducted on molecules that have different roles in drug delivery. Among these compounds, supramolecules have unique properties and have specific uses in chemotherapy.1 Crown ethers are in the category of supramolecules that have been used extensively in drug delivery. An interesting research in this field was conducted in 2017 by Morrison et al.2 They investigated 12-crown-4, 15-crown-5, and 18-crown-6 for their ability to increase the solubility of riboflavin and enhance its penetration into the cornea in order to treat the keratoconus.3 Due to the polar structure of riboflavin, its penetration into the epithelium layer is not possible (Fig. 1). Crown ethers can, through the formation of the complex with Ca2+ (Available in epithelium layer) and as riboflavin carriers, penetrate into the epithelium layer and eventually reach the stroma layer. In the stroma layer, the presence of riboflavin makes the linkbetween collagen strands and the disease improves. Material and Method:Crown ethers, riboflavin, benzalkonium chloride (BAC), ethylenediaminetetraacetic acid (EDTA) and fluorescein sodium salt were supplied by Sigma-Aldrich (Gillingham, UK).High performance liquid chromatography (HPLC) was employed to determine riboflavin solubility enhancement and in vitro experiments using Franz diffusion cells (FDC) to determine drug permeation through whole corneas. Bovine corneal opacity and permeability (BCOP) was used to determine toxicological implications from the use of crown ethers. Results: Data on the effects of crown ethers on solubility of riboflavin are presented in Tables 1. Discussion: According to the data in Table 1, it was found that 12-crown-4 at 1 mg mL-1 offered a slight reduction to the solubility of riboflavin whilst 15-crown-5 and 18-crown-6 at 1 mg mL-1 and all the investigated crown ethers at higher concentrations offered significant enhancement to riboflavin solubility, thereby increasing its availability for use in ocular drug formulations.Further experiments determined that all the crown ether solutions investigated were efficient at delivering riboflavin into the corneal stroma.

Crown ethe، riboflavin, benzalkonium chloride ،ocular drug delivery، supramolecules