title: In Vivo Assessment of Clobetasol Propionate-Loaded Lecithin-Chitosan Nanoparticles for Skin Delivery.
abstract: The aim of this work was to assess in vivo the anti-inflammatory efficacy and tolerability of clobetasol propionate (CP) loaded lecithin/chitosan nanoparticles incorporated into chitosan gel for topical application (CP 0.005%). As a comparison, a commercial cream (CP 0.05%w/w), and a sodium deoxycholate gel (CP 0.05%w/w) were also evaluated. Lecithin/chitosan nanoparticles were prepared by self-assembling of the components obtained by direct injection of soybean lecithin alcoholic solution containing CP into chitosan aqueous solution. Nanoparticles obtained had a particle size around 250 nm, narrow distribution (polydispersity index below 0.2) and positive surface charge, provided by a superficial layer of the cationic polymer. The nanoparticle suspension was then loaded into a chitosan gel, to obtain a final CP concentration of 0.005%. The anti-inflammatory activity was evaluated using carrageenan-induced hind paw edema test on Wistar rats, the effect of formulations on the barrier property of the stratum corneum were determined using transepidermal water loss measurements (TEWL) and histological analysis was performed to evaluate the possible presence of morphological changes. The results obtained indicate that nanoparticle-in-gel formulation produced significantly higher edema inhibition compared to other formulations tested, although it contained ten times less CP. TEWL measurements also revealed that all formulations have no significant disturbance on the barrier function of skin. Furthermore, histological analysis of rat abdominal skin did not show morphological tissue changes nor cell infiltration signs after application of the formulations. Taken together, the present data show that the use of lecithin/chitosan nanoparticles in chitosan gel as a drug carrier significantly improves the risk-benefit ratio as compared with sodium-deoxycholate gel and commercial cream formulations of CP.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Ege University, Bornova, 35100 Izmir, Turkey. taner.senyigit@ege.edu.tr.
authors.forename: Taner
authors.initials: T
authors.lastname: Şenyiğit
authors.affiliation: Department of Pharmacy, University of Parma, 43124 Parma, Italy. fabio.sonvico@unipr.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Sonvico
authors.affiliation: Department of Pharmacy, University of Parma, 43124 Parma, Italy. alessandra.rossi@unipr.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Department of Histology and Embriology, Faculty of Medicine, Dokuz Eylul University, Inciraltı, 35340 Izmir, Turkey. tekmen@deu.edu.tr.
authors.forename: Işıl
authors.initials: I
authors.lastname: Tekmen
authors.affiliation: Department of Pharmacy, University of Parma, 43124 Parma, Italy. santipat@unipr.it.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Santi
authors.affiliation: Department of Pharmacy, University of Parma, 43124 Parma, Italy. paolo.colombo@unipr.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Colombo
authors.affiliation: Department of Pharmacy, University of Parma, 43124 Parma, Italy. sara.nicoli@unipr.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Nicoli
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Ege University, Bornova, 35100 Izmir, Turkey. ozgen.ozer@ege.edu.tr.
authors.forename: Özgen
authors.initials: Ö
authors.lastname: Özer
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D048271:Chitosan / Q000737:chemistry; D002990:Clobetasol / Q000008:administration & dosage* / Q000494:pharmacology; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000494:pharmacology; D054709:Lecithins / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000009:adverse effects* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D054709:Lecithins; D048271:Chitosan; D002990:Clobetasol
keywords: anti-inflammatory activity; chitosan; clobetasol propionate; lecithin; nanoparticles; skin irritation; topical glucocorticoids; transepidermal water loss