Implementing Spanlastics for Improving the Ocular Delivery of Clotrimazole: In vitro Characterization, Ex vivo Permeability, Microbiological Assessment and In vivo Safety Study

Abstract

Purpose The aim of this study was to encapsulate clotrimazole (CLT), an antifungal drug with poor water solubility characteristics, into spanlastics (SPs) to provide a controlled ocular delivery of the drug. Methods Span 60 was used in the formulation of SPs with Tween 80, Pluronic F127, or Kolliphor RH40 as an edge activator (EA). The presence of EA offers more elasticity to the membrane of the vesicles which is expected to increase the corneal permeation of CLT. SPs were prepared using ethanol injection method applying 3 2 complete factorial design to study the effect of formulation variables (ratio of Span 60: EA (w/w) and type of EA) on SPs characteristics (encapsulation efficiency percent (EE%), average vesicle size (VS), polydispersity index (PDI) and zeta potential (ZP)). Design-Expert software was used to determine the optimum formulation for further investigations. Results The optimum formulation determined was S1, which contains 20 mg of Tween 80 used as an EA and 80 mg of Span 60. S1 exhibited EE% = 66.54 ± 7.57%, VS = 206.20 ± 4.95 nm, PDI = 0.39 ± 0.00 and ZP = −29.60 ± 0.99 mV. S1 showed highly elastic sphere-shaped vesicles. Furthermore, S1 displayed a sustained release profile and a higher ex vivo permeation across rabbit cornea relative to CLT suspension. Also, S1 revealed superior inhibition of Candida albicans development compared to CLT suspension applying 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction technique. Moreover, in vivo histopathological examination assured the safety of S1 after ophthalmic application in mature male albino rabbits. Conclusion Overall, the outcomes revealed the marked efficacy of SPs for ocular delivery of CLT.

Formulation of Chitosan-Coated Brigatinib Nanospanlastics: Optimization, Characterization, Stability Assessment and In-Vitro Cytotoxicity Activity against H-1975 Cell Lines

“…So, Tween ® 80 was more hydrophobic than Pluronic F127, therefore, Tween ® 80-based NSPs were more rigid by decreasing the amphiphilic property of the vesicles’ membrane, resulting in higher EE% [ 31 ]. These results are in agreement with those of Abdelbari et al [ 32 ] who reported higher EE% with Tween ® 80-based splanlastics than Pluronic F127-based NSPs for the ocular delivery of clotrimazole.…”

Fenticonazole nitrate loaded trans-novasomes for effective management of tinea corporis: design characterization, in silico study, and exploratory clinical appraisal

“…The microplate photometer (Tecan Sunrise absorbance reader, Reading, UK) was employed to calculate any color change caused by XTT decrease at 492 nm. The following is the equation used to determine inhibition % (Abdelbari et al., 2021 ): …”

Corneal targeted fenticonazole nitrate-loaded novasomes for the management of ocular candidiasis: Preparation, in vitro characterization, ex vivo and in vivo assessments

“…Hydrophobicity of stearic acid arises from its long alkyl chain (C18) along with its saturation reflecting in high phase transition temperature (Tc = 69 °C), leading to the formation of less leaky vesicles resulting in higher EE%. Regarding factor B ( p < 0.0001), increasing ratio or concentration of span 80 having low HLB (4.3) (Ruckmani & Sankar, 2010 ) due to its long alkyl chain of oleate moiety(C18) (Abdelbary et al, 2017 ), resulting in less hydrophilic holes and reducing the fluidity of the membrane by reducing the bilayers amphiphilic property (Abdelbari et al, 2021 ). Moreover, it was found that the EE% value increases upon increasing surfactant concentration which could be attributed to the added emulsification and stabilization impact of the lipid material in the presence of high surfactant concentration (Abdelbary & Fahmy, 2009 ).…”

“…The cholesterol intercalates inside the bilayer by placing the polar head toward the hydrophilic surface and the aliphatic chain parallel to the surfactant alkyl chains, accordingly PS increased (Emad Eldeeb et al, 2019 ). Also, the presence of a large amount of vesicles-forming materials relative to the hydration medium would lead to accumulation of multiple layers over each other and thus PS increased (Abdelbari et al, 2021 ).…”