Cationic polysaccharides: emerging drug delivery vehicle across the physiological mucus barrier

摘要

The mucus layer presents a physiological barrier that provides a first line of defense to the underlying organs against invading biological and chemical agents. Mainly, the mucus mesh comprises heterogeneous spacing ranging from 20 to 1800 nm across different organs, where the size filtering and interaction filtering mechanisms govern its permeability. The size filtering effect allows the permeation of particles smaller than the mesh size while retaining the large molecules. The interaction filtering mechanisms allow the penetration of neutral molecules as the positively charged molecules adhere to the negatively charged mucus layer, while the similarly charged molecules neither adhere to nor penetrate the mucus layer [1]. The presence of -COOH and/or -SO42- functional groups on the mucin proteoglycans provides an overall negative charge to the mucus layer, which determines the mucoadhesive/muco-penetration potential of rationally developed drug delivery systems. In addition, drug delivery across the respiratory mucosa counters mucociliary clearance mechanisms that further challenge drug pharmacokinetics and the maintenance of an effective therapeutic dose. Further, these factors necessitate increased dosing frequency to maintain an optimal therapeutic effect, which apparently hampers patient compliance [2].