title: Roxithromycin-loaded lipid nanoparticles for follicular targeting.
abstract: Particulate drug carriers e.g. nanoparticles (NPs) have been shown to penetrate and accumulate preferentially in skin hair follicles creating high local concentration of a drug. In order to develop such a follicle targeting system we obtained and characterized solid lipid nanoparticles (SLN) loaded with roxithromycin (ROX). The mean particle size (172±2 nm), polydisperisty index (0.237±0.007), zeta potential (-31.68±3.10 mV) and incorporation efficiency (82.1±3.0%) were measured. The long term stability of ROX-loaded SLN suspensions was proved up to 26 weeks. In vitro drug release study was performed using apparatus 4 dialysis adapters. Skin irritation test conducted using the EpiDerm™ tissue model demonstrated no irritation potential for ROX-loaded SLN. Ex vivo human skin penetration studies, employing rhodamine B hexyl ester perchlorate (RBHE) as a fluorescent dye to label the particles, revealed fluorescence deep in the skin, specifically around the hair follicles up to over 1mm depth. The comparison of fluorescence intensities after application of RBHE solution and RBHE-labelled ROX-loaded SLN was done. Then cyanoacrylate follicular biopsies were obtained in vivo and analyzed for ROX content, proving the possibility of penetration to human pilosebaceous units and delivering ROX by using SLN with the size below 200 nm.
authors.affiliation: Department of Pharmaceutical Technology, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Wosicka-Frąckowiak
authors.affiliation: Department of Pharmaceutical Technology, Medical University of Gdansk, Hallera 107, 80-416 Gdańsk, Poland. Electronic address: kcal@wp.pl.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Cal
authors.affiliation: Department of Pharmaceutical Technology, Medical University of Gdansk, Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Stefanowska
authors.affiliation: Department of Pharmaceutical Technology, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland.
authors.forename: Eliza
authors.initials: E
authors.lastname: Główka
authors.affiliation: Institute of Chemical Technology and Engineering, Poznan University of Technology, Berdychowo 4, 60-695 Poznań, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Nowacka
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Wiktoria
authors.initials: W
authors.lastname: Struck-Lewicka
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia.
authors.forename: Biljana
authors.initials: B
authors.lastname: Govedarica
authors.affiliation: Dr Irena Eris Centre for Science and Research, Puławska 107 A, 02-595 Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Pasikowska
authors.affiliation: Dr Irena Eris Centre for Science and Research, Puławska 107 A, 02-595 Warsaw, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Dębowska
authors.affiliation: Institute of Chemical Technology and Engineering, Poznan University of Technology, Berdychowo 4, 60-695 Poznań, Poland.
authors.forename: Teofil
authors.initials: T
authors.lastname: Jesionowski
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia.
authors.forename: Stane
authors.initials: S
authors.lastname: Srčič
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Michał Jan
authors.initials: MJ
authors.lastname: Markuszewski
mesh_terms: D000279:Administration, Cutaneous; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D065546:Drug Liberation; D004355:Drug Stability; D018859:Hair Follicle / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D015575:Roxithromycin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D012869:Skin Absorption
chemical_list: D004337:Drug Carriers; D008055:Lipids; D015575:Roxithromycin
keywords: Differential stripping; Ex vivo skin penetration; Hair follicles; In vivo skin penetration; Lipid nanoparticles; Roxithromycin