title: Ufasomes nano-vesicles-based lyophilized platforms for intranasal delivery of cinnarizine: preparation, optimization, ex-vivo histopathological safety assessment and mucosal confocal imaging.
abstract: To circumvent the low and erratic absorption of orally administrated cinnarizine (CN), intranasal lyophilized gels containing unsaturated fatty acid liposomes (ufasomes) and encapsulating CN were prepared from oleic acid using a simple assembling strategy. The effects of varying drug concentration and cholesterol percentage on ufasomes size, polydispersity index and entrapment efficiency were investigated using 3(1)4(1) full factorial design. The optimized ufasomes that contained 14% cholesterol relative to oleic acid displayed spherical morphology with average size of 788 nm and entrapment efficiency of 80.49%. To overcome the colloidal instability of CN-loaded ufasomes dispersions and their short residence time in the nasal cavity, the ufasomes were incorporated into mucoadhesive hydrogels that were lyophilized into unit dosage forms for accurate dosing. Scanning electron micrographs of the lyophilized gel revealed that the included ufasomes were intact, non-aggregating and maintained their spherical morphology. Rheological characterization of reconstituted ufasomal lyophilized gel ensured ease of application. Furthermore, the gel induced minor histopathological alterations in sheeps' nasal mucosa. Ex-vivo confocal laser imaging confirmed the ability of ufasomes to penetrate deep through nasal mucosa layers. The results highlighted in the current work confirm the feasibility of using CN-loaded ufasomal gels for intranasal drug delivery.
authors.affiliation: a Department of Pharmaceutical Technology , National Research Center , Dokki , Cairo , Egypt and.
authors.forename: Alaa Hamed
authors.initials: AH
authors.lastname: Salama
authors.affiliation: b Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Cairo University , Cairo , Egypt.
authors.forename: Mona Hassan
authors.initials: MH
authors.lastname: Aburahma
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D002936:Cinnarizine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation / Q000187:drug effects / Q000502:physiology; D005612:Freeze Drying / Q000379:methods; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008081:Liposomes; D018613:Microscopy, Confocal / Q000379:methods; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012756:Sheep
chemical_list: D006634:Histamine H1 Antagonists; D008081:Liposomes; D002936:Cinnarizine
keywords: Cinnarizine; confocal laser scanning microscopy; intranasal drug delivery; oleic acid; ufasomal lyophilized gel; ufasomes; unsaturated fatty acid vesicles