title: Enhanced stability and dermal delivery of hydroquinone using solid lipid nanoparticles.
abstract: Hydroquinone (HQ), a well-known anti-hyperpigmentation agent suffers from (a) instability due to rapid oxidation, (b) insufficient skin penetration because of hydrophilic structure, and (c) severe side effects as a results of systemic absorption. This study aimed to load HQ into solid lipid nanoparticles (SLNs) to overcome the mentioned drawbacks for the efficient treatment of hyperpigmentation. The optimized SLN formulation was prepared by hot melt homogenization method and fully characterized by various techniques. The ability of SLNs in dermal delivery of HQ was assessed through the excised rat skin. The optimized HQ-loaded SLNs (particle size of 86 nm, encapsulation efficiency% of 89.5% and loading capacity% of 11.2%) exhibited a good physicochemical stability during a period of five months. XRD and DSC results showed that HQ was dispersed in an amorphous state, confirming uniform drug dispersion in the SLNs structure and embedment of drug in the solid lipid matrix. In vitro penetration studies showed almost 3 times higher drug accumulation in the skin and 6.5 times lower drug entrance to receiving compartment of Franz diffusion cell from HQ-loaded SLN hydrogel compared with HQ Carbopol made hydrogel. These results indicated the better HQ localization in the skin and its lower systemic absorption. It was concluded that SLN is a promising colloidal drug carrier for topical administration of HQ in the treatment of hyperpigmentation due to suitable HQ loading value in spite of its hydrophilic structure, high stability against oxidation and appropriate skin penetration along with the low systemic absorption.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Ghanbarzadeh
authors.affiliation: Research Center for Pharmaceutical Nanotechnology and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Hariri
authors.affiliation: Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Kouhsoltani
authors.affiliation: Dermatology & Dermopharmacy Research Team and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Shokri
authors.affiliation: Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Yousef
authors.initials: Y
authors.lastname: Javadzadeh
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Golgasht Ave, Tabriz, Iran. Electronic address: Hamishehkarh@tbzmed.ac.ir.
authors.forename: Hamed
authors.initials: H
authors.lastname: Hamishehkar
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006873:Hydroquinones / Q000008:administration & dosage*; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism*; D014961:X-Ray Diffraction
chemical_list: D006873:Hydroquinones; D008055:Lipids; C031927:hydroquinone
keywords: Dermal drug delivery; Hydroquinone; SLN; Solid lipid nanoparticle