title: Potential transbuccal delivery of l-DOPA methylester prodrug: stability in the environment of the oral cavity and ability to cross the mucosal tissue.
abstract: Levodopa (l-DOPA) is the most effective pharmacologic agent in Parkinson's disease and remains the "gold standard". Nevertheless, in long-term treatments, dyskinesias and motor complications can emerge. In this work, the combined use of l-DOPA methylester hydrochloride prodrug (LDME) with transbuccal drug delivery was supposed as a good alternative method to optimize the bioavailability of l-DOPA, to maintain constant plasma levels and to decrease the drug unwanted effects. The effects of environmental pH on buccal delivery of LDME were evaluated ex vivo. The increase of pH value from 5.8 to 6.2 implies an improvement of drug permeation. Since the pH increase causes the raising of hydrolytic conversion of LDME to l-DOPA, the pH value 6.2 was considered as a good compromise between drug stability and permeation rate. It was found that during the passage through the biological tissue, LDME undergoes a primary conversion to l-DOPA catalyzed by membrane's enzymes. Supplementation of delivery with Tween 80® produces substantial enhancement of LDME passage through the membrane. The drug could be loaded in the IntelliDrug mechatronic device, released close to the buccal mucosa, so achieving and maintaining constant therapeutic blood levels for extensive time.
authors.affiliation: a Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF) , University of Palermo , Palermo , Italy and.
authors.forename: Anna Lisa
authors.initials: AL
authors.lastname: Scaturro
authors.affiliation: a Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF) , University of Palermo , Palermo , Italy and.
authors.forename: Viviana
authors.initials: V
authors.lastname: De Caro
authors.affiliation: b Dipartimento di Discipline Chirurgiche , Oncologiche e Stomatologiche (Di.Chir.On.S.), University of Palermo , Palermo , Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Campisi
authors.affiliation: a Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF) , University of Palermo , Palermo , Italy and.
authors.forename: Libero Italo
authors.initials: LI
authors.lastname: Giannola
mesh_terms: D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D007980:Levodopa / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D009055:Mouth; D009061:Mouth Mucosa / Q000378:metabolism*; D010300:Parkinson Disease / Q000188:drug therapy*; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000978:Antiparkinson Agents; D011355:Prodrugs; D007980:Levodopa; C035420:levodopa methyl ester
keywords: Buccal permeation; chemical stability; intellidrug device; prodrugs; transmucosal drug delivery