Mucoadhesive and cohesive properties of poly(acrylic acid)-cysteine conjugates with regard to their molecular mass.
The objective of this study was to evaluate the influence of the molecular mass and accordingly the polymer chain length on mucoadhesion and cohesion of thiolated polymers. Linear poly(acrylic acid)-cysteine (PAA-Cys) conjugates of 2-, 45-, 250- and 450 kDa (PAA(2)-Cys, PAA(45)-Cys, PAA(250)-Cys and PAA(450)-Cys) and polycarbophil-cysteine (PCP-Cys, 750-3000 kDa), all displaying on average 404.1+/-65.5 microMol thiol groups per gram polymer were compressed into tablets to perform disintegration tests, mucoadhesion studies and viscosity measurements. Moreover, the influence of free unbound cysteine on mucoadhesion was evaluated. Disintegration tests showed a stability of the tablets as following: PAA(2)-Cys<PAA(45)-Cys<PAA(250)-Cys<PAA(450)-Cys=PCP-Cys. According to tensile studies and tests on the rotating cylinder the following rank order in mucoadhesive properties could be established: PAA(2)-Cys<PAA(45)-Cys<PCP-Cys<PAA(250)-Cys<PAA(450)-Cys. Evidence for the formation of disulphide bonds between thiolated polymers and mucin could be provided by the addition of free cysteine resulting in strongly decreased mucoadhesion and by viscosity studies showing comparatively higher viscosity of conjugate/mucin mixtures than of unthiolated polymer/mucin mixtures. The results of the present study contribute to the development of new polymers displaying further improved mucoadhesive properties.
Leitner
V M
VM
Institute of Pharmaceutical Technology and Biopharmaceutics, Centre of Pharmacy, University of Vienna, Althanstr 14, A-1090, Vienna, Austria.
Marschütz
M K
MK
Bernkop-Schnürch
A
A
D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D002626:Chemistry, Pharmaceutical; D003545:Cysteine / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D005752:Gastric Mucins / Q000737:chemistry* / Q000502:physiology; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000502:physiology*; D008970:Molecular Weight; D013552:Swine; D013607:Tablets; D013718:Tensile Strength; D013997:Time Factors; D000267:Tissue Adhesions
D000180:Acrylic Resins; D005752:Gastric Mucins; D013607:Tablets; C006903:carbopol 940; D003545:Cysteine