Minimization of Local and Systemic Adverse Effects of Topical Glucocorticoids by Nanoencapsulation: In Vivo Safety of Hydrocortisone–Hydroxytyrosol Loaded Chitosan Nanoparticles. Issue 12 (8th October 2015)

• Record Type: Journal Article
• Authors: Siddique, Muhammad Irfan; Katas, Haliza; Iqbal Mohd Amin, Mohd Cairul; Ng, Shiow‐Fern; Zulfakar, Mohd Hanif; Buang, Fhataheya; Jamil, Adawiyah
• Is Part Of: Journal of pharmaceutical sciences. Volume 104:Issue 12(2015:Dec.)
• Page Start: 4276
• Page End: 4286
• Publication Date: 2015-10-08
• Subjects: chronic dermal toxicity -- corticosteroids -- chitosan -- nanoparticles -- nanotoxicology -- nanoencapsulation -- skin -- targeted drug delivery -- biodegradable polymers; Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.24666
• Languages: English
• ISSNs: 0022-3549

Abstract

Abstract : Hydrocortisone (HC) is a topical glucocorticoid for the treatment of atopic dermatitis (AD); the local as well as systemic side effects limit its use. Hydroxytyrosol (HT) is a polyphenol present in olive oil that has strong antimicrobial and antioxidant activities. HC–HT coloaded chitosan nanoparticles (HC–HT CSNPs) were therefore developed to improve the efficacy against AD. In this study, HC–HT CSNPs of 235 ± 9 nm in size and with zeta potential +39.2 ± 1.6 mV were incorporated into aqueous cream (vehicle) and investigated for acute dermal toxicity, dermal irritation, and repeated dose toxicity using albino Wistar rats. HC–HT CSNPs exhibited LD50 > 125 mg/body surface area of active, which is 100‐fold higher than the normal human dose of HC. Compared with the commercial formulation, 0.5 g of HC–HT CSNPs did not cause skin irritation, as measured by Tewameter®, Mexameter®, and as observed visually. Moreover, no‐observed‐adverse‐effect level was observed with respect to body weight, organ weight, feed consumption, blood hematological and biochemical, urinalysis, and histopathological parameters at a dose of 1000 mg/body surface area per day of HC–HT CSNPs for 28 days. This in vivo study demonstrated that nanoencapsulation significantly reduced the toxic effects of HC and this should allow further clinical investigations. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:4276–4286, 2015