title: Design and optimization of surfactant-based nanovesicles for ocular delivery of Clotrimazole.
abstract: The objective of this study was to develop an efficient ocular nanovesicular carrier providing a controlled delivery of Clotrimazole (CLT); a water insoluble antifungal drug. The nanovesicular carriers were formulated using Span 60 with one of the following edge activators (EA): Tween 80 (TW80), sodium cholate (SC) or sodium deoxycholate (SDC). A 3(2) full factorial design was used to study the effect of two independent variables, namely, the type of EA and the ratio of Span 60 to EA. The effects of these parameters on the mean particle size, entrapment efficiency (EE) and zeta potential (ZP) were investigated as dependent variables. Then, optimization was performed producing the best optimized formulation composed of SDC as an EA at the ratio of 90:10 (Span 60:EA) with an average diameter of 479.60 nm, EE of 87.92% and ZP of -33.7 mV. The optimized nanovesicular carriers appeared as spherical unilamillar vesicles with CLT in an amorphous state as evidenced by the differential scanning calorimetry study. The antifungal activity against Candida albicans compared to niosomal formulation as well as the CLT suspension was determined. CLT-loaded nanovesicular carriers displayed sustained antifungal effect over 12 h. The AUC of the optimized formulation was 3.09 times more than that of drug suspension with no sign of irritation after testing for ocular tolerance. Therefore, the present study showed the feasibility of using non-ionic surfactant nanovesicles as carrier systems for prolonged ocular delivery of CLT.
authors.affiliation: Department of Pharmaceutical Technology, National Research Center, Cairo, Egypt. mona-basha@hotmail.com
authors.forename: Mona
authors.initials: M
authors.lastname: Basha
authors.forename: Sameh Hosam
authors.initials: SH
authors.lastname: Abd El-Alim
authors.forename: Rehab N
authors.initials: RN
authors.lastname: Shamma
authors.forename: Ghada E A
authors.initials: GE
authors.lastname: Awad
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage*; D002176:Candida albicans / Q000187:drug effects; D003022:Clotrimazole / Q000008:administration & dosage*; D003840:Deoxycholic Acid / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D005123:Eye / Q000187:drug effects*; D006601:Hexoses / Q000737:chemistry; D008297:Male; D058726:Nanoconjugates; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D011817:Rabbits; D020358:Sodium Cholate / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D006601:Hexoses; D058726:Nanoconjugates; D011136:Polysorbates; D013501:Surface-Active Agents; D003840:Deoxycholic Acid; D003022:Clotrimazole; D020358:Sodium Cholate; C009298:sorbitan monostearate