In vitro evaluation of the bioadhesive properties of hydrophobic polybasic gels containing N,N-dimethylaminoethyl methacrylate-co-methyl methacrylate.

The bioadhesive properties of the hydrophobic, basic polyelectrolyte hydrogel disks containing crosslinked N,N-dimethylaminoethyl methacrylate-co-methyl methacrylate 30/70mol% were evaluated in vitro using gastric (pH 1.2), sublingual (pH 6.5), vaginal (pH 4.0) and intestinal (pH 7.5) pig's mucosas. Adhesive strength was measured using a modified Du Noüy tensiometer by measuring the force of detachment between a gel disk and the respective mucosa. The effect of crosslinker content in the gel was evaluated. It was found an increase in the adhesive strength with the increase of crosslinker content in the pH range of 4.0-7.5. For the evaluation at pH 1.2 (gastric mucosa) the opposite behavior was observed. The results indicate that initial bioadhesive contact may be the result of surface energy effects and/or electrostatic interactions of oppositely charged groups between mucin and the gel. In some cases, mucus dehydration may also be involved. When the gel is swollen, chain interpenetration also plays a roll in the bioadhesive interaction. The gels presented bioadhesive forces in gastric and vaginal mucosas (acidic medium), similar to the adhesive forces of well-known bioadhesives such as hydroxymethylcellulose and sodium alginate to the intestinal mucosa. The results indicate that hydrophobic polybasic gels present bioadhesive properties that make them suitable for site specific, pH controlled drug delivery.

[1]  A. Slomiany,et al.  Isolation of fatty acids covalently bound to the gastric mucus glycoprotein of normal and cystic fibrosis patients. , 1983, Biochemical and biophysical research communications.

[2]  Nikolaos A. Peppas,et al.  Surface, interfacial and molecular aspects of polymer bioadhesion on soft tissues , 1985 .

[3]  S. Mortazavi,et al.  An in-vitro method for assessing the duration of mucoadhesion , 1994 .

[4]  Donald E. Chickering,et al.  Biologically erodable microspheres as potential oral drug delivery systems , 1997, Nature.

[5]  C. Wong,et al.  Formulation and evaluation of controlled release Eudragit buccal patches. , 1999, International journal of pharmaceutics.

[6]  L. Nielsen,et al.  Bioadhesive drug delivery systems: I. Characterisation of mucoadhesive properties of systems based on glyceryl mono-oleate and glyceryl monolinoleate , 1998 .

[7]  S. Mortazavi,et al.  An investigation into the role of water movement and mucus gel dehydration in mucoadhesion , 1993 .

[8]  J. Kost Pulsed and Self-Regulated Drug Delivery , 1990 .

[9]  A. Perkins,et al.  Evaluation of the clearance characteristics of bioadhesive systems in humans. , 1999, International journal of pharmaceutics.

[10]  S. H. Leung,et al.  Polyanionic Polymers in Bio- and Mucoadhesive Drug Delivery , 1992 .

[11]  E. Topp,et al.  Evaluation of mucoadhesive properties of hyaluronic acid benzyl esters , 1994 .

[12]  H. Sharma,et al.  An investigation of the parameters influencing the bioadhesive properties of Myverol 18-99/water gels. , 1997, Biomaterials.

[13]  R. Siegel,et al.  Hydrophobic Weak Polybasic Gels: Factors Controlling Swelling Equilibria , 1991 .

[14]  H. Merkle,et al.  Evaluation of laminated muco-adhesive patches for buccal drug delivery , 1989 .

[15]  A. Shatkay,et al.  Potentiometric Titrations of Polyelectrolytes with Separation of Phases , 1966 .

[16]  E. Mathiowitz,et al.  Nanosphere based oral insulin delivery. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[17]  R. Siegel,et al.  pH-Controlled release from hydrophobic/polyelectrolyte copolymer hydrogels , 1988 .

[18]  Ronald A. Siegel,et al.  pH-Dependent Equilibrium Swelling Properties of Hydrophobic Polyelectrolyte Copolymer Gels , 1988 .

[19]  E. Mathiowitz,et al.  Bioadhesive microspheres. I: A novel electrobalance-based method to study adhesive interactions between individual microspheres and intestinal mucosa , 1995 .