title: Transdermal anti-inflammatory activity of bilayer film containing olive compound hydroxytyrosol: physical assessment, in vivo dermal safety and efficacy study in Freund's adjuvant-induced arthritic rat model.
abstract: Previous studies have shown that hydroxytyrosol (HT) can be a potential alternative therapeutic agent for the treatment of rheumatoid arthritis (RA). However, HT is extensively metabolized following oral administration, which leads to formulating HT in a topical vehicle to prolong drug action as well as to provide a localized effect. Hidrox-6 is a freeze-dried powder derived from fresh olives and contains a high amount of HT (∼3%) and other polyphenols. Alginate bilayer films containing 5% and 10% Hidrox-6 were formulated. The films were characterized with respect to their physical, morphology, rheological properties; drug content uniformity; and in vitro drug release. Acute dermal irritancy tests and a skin sensitization study were carried out in rats. An efficacy study of the bilayer films for RA was conducted using Freund's adjuvant-induced polyarthritis rats. Animal data showed that the bilayer film formulations did not cause skin irritancy. The efficacy in vivo results showed that the Hidrox-6 bilayer films lowered the arthritic scores, paw and ankle circumference, serum IL-6 level and cumulative histological scores compared with those measured for controls. The topical Hidrox-6 bilayer films improve synovitis and inflammatory symptoms in RA and can be a potential alternative to oral RA therapy.
authors: a Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia , Kuala Lumpur , Malaysia.
authors: Shiow-Fern
authors: SF
authors: Ng
authors: a Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia , Kuala Lumpur , Malaysia.
authors: Leong-Seng
authors: LS
authors: Tan
authors: a Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia , Kuala Lumpur , Malaysia.
authors: Fhataheya
authors: F
authors: Buang
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D005620:Freund's Adjuvant; D008297:Male; D031658:Olea; D009924:Organ Culture Techniques; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D010936:Plant Extracts; C005975:3,4-dihydroxyphenylethanol; D005620:Freund's Adjuvant; D010626:Phenylethyl Alcohol
keywords: Freund’s adjuvant-induced rats; Hidrox; Hydroxytyrosol; alginate; bilayer film; rheumatoid arthritis