title: A mechanistic based approach for enhancing buccal mucoadhesion of chitosan.
abstract: Mucoadhesive buccal drug delivery systems can enhance rapid drug absorption by providing an increased retention time at the site of absorption and a steep concentration gradient. An understanding of the mechanisms behind mucoadhesion of polymers, e.g. chitosan, is necessary for improving the mucoadhesiveness of buccal formulations. The interaction between chitosan of different chain lengths and porcine gastric mucin (PGM) was studied using a complex coacervation model (CCM), isothermal titration calorimetry (ITC) and a tensile detachment model (TDM). The effect of pH was assessed in all three models and the approach to add a buffer to chitosan based drug delivery systems is a means to optimize and enhance buccal drug absorption. The CCM demonstrated optimal interactions between chitosan and PGM at pH 5.2. The ITC experiments showed a significantly increase in affinity between chitosan and PGM at pH 5.2 compared to pH 6.3 and that the interactions were entropy driven. The TDM showed a significantly increase in strength of adhesion between chitosan discs and an artificial mucosal surface at pH 5.2 compared to pH 6.8, addition of PGM increased the total work of adhesion by a factor of 10 as compared to the wetted surface without PGM. These findings suggest that chitosan and PGM are able to interact by electrostatic interactions and by improving the conditions for electrostatic interactions, the adhesion between chitosan and PGM becomes stronger. Also, the three complementary methods were utilized to conclude the pH dependency on mucoadhesiveness.
authors.affiliation: Section for Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Emil
authors.initials: E
authors.lastname: Meng-Lund
authors.affiliation: Section for Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Muff-Westergaard
authors.affiliation: Section for Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Camilla
authors.initials: C
authors.lastname: Sander
authors.affiliation: Section for Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Madelung
authors.affiliation: Section for Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: jette.jacobsen@sund.ku.dk.
authors.forename: Jette
authors.initials: J
authors.lastname: Jacobsen
mesh_terms: D000268:Adhesiveness; D000278:Administration, Buccal; D000818:Animals; D002151:Calorimetry / Q000379:methods; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D019277:Entropy; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D009077:Mucins / Q000378:metabolism*; D055672:Static Electricity; D013552:Swine
chemical_list: D004337:Drug Carriers; D009077:Mucins; D048271:Chitosan
keywords: 2-(N-morpholino)ethanesulfonic acid; Buccal mucoadhesion; CCM; CHITOPHARM(®) L; CHITOPHARM(®) M; CHITOPHARM(®) S; CL; CM; CS; Chitosan; Complex coacervation; HWS; ITC; Isothermal titration calorimetry; MES; Mucin; PGM; TDM; Texture analyzer; complex coacervation model; human whole saliva; isothermal titration calorimetry; porcine gastric mucin; tensile detachment model