title: Evaluation of alternative strategies to optimize ketorolac transdermal delivery.
abstract: In the present study, 2 alternative strategies to optimize ketorolac transdermal delivery, namely, prodrugs (polyoxyethylene glycol ester derivatives, I-IV) and nanostructured lipid carriers (NLC) were investigated. The synthesized prodrugs were chemically stable and easily degraded to the parent drug in human plasma. Ketorolac-loaded NLC with high drug content could be successfully prepared. The obtained products formulated into gels showed a different trend of drug permeation through human stratum corneum and epidermis. Particularly, skin permeation of ester prodrugs was significantly enhanced, apart from ester IV, compared with ketorolac, while the results of drug release from NLC outlined that these carriers were ineffective in increasing ketorolac percutaneous absorption owing to a high degree of mutual interaction between the drug and carrier lipid matrix. Polyoxyethylene glycol esterification confirmed to be a suitable approach to enhance ketorolac transdermal delivery, while NLC seemed more appropriate for sustained release owing to the possible formation of a drug reservoir into the skin.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Catania, viale A. Doria 6, 95125, Catania, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Puglia
authors.forename: Rosanna
authors.initials: R
authors.lastname: Filosa
authors.forename: Antonella
authors.initials: A
authors.lastname: Peduto
authors.forename: Paolo
authors.initials: P
authors.lastname: de Caprariis
authors.forename: Luisa
authors.initials: L
authors.lastname: Rizza
authors.forename: Francesco
authors.initials: F
authors.lastname: Bonina
authors.forename: Paolo
authors.initials: P
authors.lastname: Blasi
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D020910:Ketorolac / Q000008:administration & dosage* / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage* / Q000378:metabolism; D012869:Skin Absorption
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D011355:Prodrugs; D020910:Ketorolac