title: Minimization of Local and Systemic Adverse Effects of Topical Glucocorticoids by Nanoencapsulation: In Vivo Safety of Hydrocortisone-Hydroxytyrosol Loaded Chitosan Nanoparticles.
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.
authors.affiliation: Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia.
authors.forename: Muhammad Irfan
authors.initials: MI
authors.lastname: Siddique
authors.affiliation: Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia. Electronic address: haliz12@hotmail.com.
authors.forename: Haliza
authors.initials: H
authors.lastname: Katas
authors.affiliation: Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia.
authors.forename: Mohd Cairul Iqbal Mohd
authors.initials: MCIM
authors.lastname: Amin
authors.affiliation: Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia.
authors.forename: Shiow-Fern
authors.initials: SF
authors.lastname: Ng
authors.affiliation: Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia.
authors.forename: Mohd Hanif
authors.initials: MH
authors.lastname: Zulfakar
authors.affiliation: Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia.
authors.forename: Fhataheya
authors.initials: F
authors.lastname: Buang
authors.affiliation: Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur 56000, Malaysia.
authors.forename: Adawiyah
authors.initials: A
authors.lastname: Jamil
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control*; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects* / Q000737:chemistry*; D006854:Hydrocortisone / Q000009:adverse effects / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010626:Phenylethyl Alcohol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012449:Safety; D063465:Skin Cream / Q000009:adverse effects / Q000737:chemistry; D012871:Skin Diseases / Q000139:chemically induced
chemical_list: D005938:Glucocorticoids; C005975:3,4-dihydroxyphenylethanol; D048271:Chitosan; D010626:Phenylethyl Alcohol; D006854:Hydrocortisone
keywords: biodegradable polymers; chitosan; chronic dermal toxicity; corticosteroids; nanoencapsulation; nanoparticles; nanotoxicology; skin; targeted drug delivery