Abstract
Buccal mucosa has recently received much attention as a potential route for systemic delivery of drugs, including biologics and vaccines. The aim of this work was to gain insight into the mechanism of fatty acids as buccal permeation enhancers, by studying the effect of a series of medium and long chain fatty acids on the permeation of a model high molecular weight and hydrophilic molecule, fluorescein isothiocyanate labelled dextran (FD-4, m.w. 4 kDa) across porcine esophageal epithelium. A parabolic relationship between fatty acid lipophilicity and enhancement was obtained, regardless of the presence and number of double bonds. The relationship, which resembles the well-known relationship between permeability and lipophilicity of transdermal delivery, presents a maximum value in correspondence of C10 (logP approx. 4). This is probably the ideal lipophilicity for the fatty acid to interact with the lipid domains of the mucosa. When the same analysis was performed on skin data, the same trend was observed, although the maximum value was reached for C12 (logP approx. 5), in agreement with the higher lipophilicity of the skin. The results obtained in the present work represent a significant advancement in the understanding of the mechanisms of action of fatty acids as buccal penetration enhancers.
Highlights
Buccal mucosa has recently received much attention as a potential route for systemic delivery of drugs, including biologics [1] and vaccines [2]
When the same analysis was performed on skin data, the same trend was observed, the maximum value was reached for C12, in agreement with the higher lipophilicity of the skin
Despite the interest obtained in transdermal delivery, they have received a limited attention for buccal delivery, concentrated mainly on oleic acid; oleic acid was successfully used to increase the permeation of small molecules such as propranolol [9], buspirone [10] and lidocaine [11], whereas it was ineffective in the case of 5-FU [12] and didanosine [13]
Summary
Buccal mucosa has recently received much attention as a potential route for systemic delivery of drugs, including biologics [1] and vaccines [2]. Concerning the mechanism of action, the following have been proposed, without direct evidence [6]: change of membrane fluidity, membrane destabilization due to cholesterol dissolution, disturbance of the lipid packing [4] and increase in partitioning. The latter can be of considerable influence in the case of basic permeants, such as propranolol [17], metaproterenol [18] or naphazoline [19], which can interact with fatty acids forming ion pairs, whose partitioning in the lipophilic barrier is increased
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
