title: Dermal and ocular safety of the new phospholipase A2 inhibitors PX-18 and PX-13 formulated as drug nanosuspension.
abstract: PX-18 and PX-13 are new secreted phospholipase A2 inhibitors. An increased expression of secreted phospholipase A2 in psoriatic epidermis and dermis was reported in the literature, hence the dermal application of PX-18 and PX-13 seems to be a promising approach for psoriasis treatment. Both compounds are practically insoluble in aqueous media and hard to formulate using conventional techniques. Therefore, nanosuspensions were prepared by high pressure homogenization. Pre-clinical skin and eye irritation tests were performed with PX-18 and PX-13 bulk material and 5% (w/w) PX-18 and PX-13 nanosuspensions using the EPISKIN and the HET-CAM test to aid safety assessment and to facilitate the design of safe and efficient human studies. It could be shown that nanosuspensions with an active content of 5% (w/w) with a particle size well in the nanometer range can be produced applying high pressure homogenisation. The results of the EPISKIN test allow the classification of PX-18 and PX-13 bulk material and the according nanosuspensions as non irritant to the skin. According to the test protocol applied for the HET-CAM test, the bulk material of the new secreted phospholipase A2 inhibitors as well as the nanosuspensions can be classified as non/slightly irritant to the eye.
authors.affiliation: Department of Pharmaceutical Technology, Biopharmaceutics and Nutricosmetics, Freie Universität Berlin, Kelchstrasse 31, 12169 Berlin, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Pardeike
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Müller
mesh_terms: D000476:Alkanesulfonates / Q000009:adverse effects*; D017738:Alkanesulfonic Acids / Q000009:adverse effects*; D000818:Animals; D001798:Blood Proteins / Q000008:administration & dosage*; D002645:Chickens; D004337:Drug Carriers / Q000009:adverse effects*; D005123:Eye / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D053758:Nanoparticles / Q000009:adverse effects*; D009829:Oleic Acids / Q000009:adverse effects*; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D013535:Suspensions
chemical_list: C545517:2-(N,N-bis(oleoyloxyethyl)amino)-1-ethanesulfonic acid; D000476:Alkanesulfonates; D017738:Alkanesulfonic Acids; D001798:Blood Proteins; D004337:Drug Carriers; D009829:Oleic Acids; C400481:PLIalpha; C105902:PX 13; D013535:Suspensions