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.

Enhanced In Situ Availability of Aphanizomenon Flos-Aquae Constituents Entrapped in Buccal Films for the Treatment of Oxidative Stress-Related Oral Diseases: Biomechanical Characterization and In Vitro/Ex Vivo Evaluation

“…In order to evaluate the ability of AFA’s to activate to permeate mucosa and reach plasmatic environment, ex vivo permeation studies were performed using vertical Franz type diffusion cells. Therefore, porcine buccal and sublingual mucous membranes were chosen, due to their similarities with human epithelia in terms of lipid content, composition, morphology, and thickness [67].…”

Mucoadhesive Polymeric Films to Enhance Barbaloin Penetration Into Buccal Mucosa: a Novel Approach to Chemoprevention

“…(Milan, Italy). The simulated salivary fluid (pH 6.8) was prepared by dissolving KCl (1.50 g), KSCN (0.54 g), NaH 2 PO 4 ·H 2 O (0.50 g), NaHCO 3 (1.50 g), and lactic acid (0.90 g) in 1 l of distilled water (24,25). Phosphate-buffered saline (PBS) Ca 2+ and Mg 2+ -free solution (pH 7.4) was prepared by dissolving KH 2 PO 4 (0.144 g), anhydrous Na 2 HPO 4 (0.795 g), and NaCl (9.0 g) in 1 l of distilled water.…”

Intraoral medical devices for sustained drug delivery

“…Giannola et al [ 28 ] conducted an in vivo study on pigs with galantamine intended to treat Alzheimer’s dementia and highlighted the advantage of this method of treatment compared to injectable formulations. Scaturro et al [ 75 ] evaluated the effect of pH on the buccal delivery of levodopa methyl ester prodrug (levodopa, the most effective pharmacologic agent in Parkinson’s disease) in ex vivo permission behavior (to use it as a drug model in IntelliDrug® mechatronic device). However, further clinical studies are needed to confirm the use of this approach as a new effective tool for the maintenance of constant dopamine stimulation (the main goal in the treatment of Parkinson’s disease).…”