title: Enhancement of 8-methoxypsoralen topical delivery via nanosized niosomal vesicles: Formulation development, in vitro and in vivo evaluation of skin deposition.
abstract: The aim of the present study is to enhance the skin penetration and deposition of 8-methoxypsoraln (8-MOP) via niosomal vesicles to increase its local efficacy and safety. 8-MOP niosomes were prepared by the thin film hydration method using Span 60 or Span 40 along with cholesterol at five different molar ratios. The obtained vesicles revealed high entrapment efficiencies (83.04-89.90%) with nanometric vesicle diameters (111.1-198.8nm) of monodisperse distribution (PDI=0.145-0.216), zeta potential values <-48.3mV and spherical morphology under transmission electron microscopy. Optimized niosomal formulations depicted a biphasic in vitro release pattern in phosphate buffer (pH 5.5)/ethanol (7:3v/v) and displayed good physical stability after storage for 6 months at room (20-25°C) and refrigeration (4-8°C) temperatures. The two optimized formulations were incorporated in 5% sodium carboxy methylcellulose based hydrogel matrix which showed optimum pH values (7.37-7.39), pseudoplastic with thixotropic rheological behavior and more retarded 8-MOP release, by 23.82 and 14.89%, compared to niosomal vesicles after 24h. In vitro drug permeation and deposition studies, using rat skins, revealed promoted penetration and accumulation of 8-MOP after 8h. The skin penetration was further confirmed in vivo by confocal laser scanning microscopy, after 2h application period using rhodamine-loaded niosomal hydrogels compared to plain rhodamine hydrogel, as a florescence marker. Therefore, enhanced permeation and skin deposition of 8-MOP delivered by niosomes may help in improving the efficacy and safety of long-term treatment with 8-MOP.
authors.affiliation: Pharmaceutical Technology Department, National Research Centre, Dokki, Cairo 12622, Egypt. Electronic address: aa.kassem@hotmail.com.
authors.forename: Ahmed Alaa
authors.initials: AA
authors.lastname: Kassem
authors.affiliation: Pharmaceutical Technology Department, National Research Centre, Dokki, Cairo 12622, Egypt.
authors.forename: Sameh Hosam
authors.initials: SH
authors.lastname: Abd El-Alim
authors.affiliation: Pharmaceutical Technology Department, National Research Centre, Dokki, Cairo 12622, Egypt.
authors.forename: Marwa Hasanein
authors.initials: MH
authors.lastname: Asfour
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004355:Drug Stability; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000648:ultrastructure; D008297:Male; D008730:Methoxsalen / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D010316:Particle Size; D051381:Rats; D012212:Rheology; D012869:Skin Absorption
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D008730:Methoxsalen
keywords: 8-methoxypsoralen; Confocal laser scanning microscopy; Hydrogel; Niosomes; Skin permeation; Topical delivery