Evaluation of mucoadhesive properties of hyaluronic acid benzyl esters

Abstract

Mucoadhesive properties of hyaluronic acid (HA) benzyl esters were evaluated. The vertical tensile force of detachment of polymer films from porcine gastric mucosal surface was measured with a microdisplacement transducer. The HA esters, namely, HYAFF 11 p25 (25% benzyl ester, 75% sodium salt), HYAFF 11 p50 (50% benzyl ester, 50% sodium salt), HYAFF 11 p75 (75% benzyl ester, 25% sodium salt) and HYAFF 11 (100% benzyl ester), were compared to glass (negative control) and to two positive controls, polycarbophil (PC) and hydroxypropylmethylcellulose (HPMC). Measurements were made for polymer films hydrated in a pH 1.2 medium, in Tyrode solution (pH 7.8) and for unhydrated films. When hydrated at pH 1.2, the more hydrophilic polymers (HPMC, HYAFF 11 p25, HYAFF 11 p50 and PC) showed significantly greater adhesion (2720–4192 dyn/cm 2) than the negative control (1980 dyn/cm 2). When hydrated at pH 7.8, only HPMC (3801 dyn/cm 2) and HYAFF 11 p25 (3198 dyn/cm 2) showed greater adhesion than the negative control. PC adhesion was significantly lower than at pH 1.2. The ionized state of PC, as well as mucus glycoprotein residues at this pH (7.8), may cause charge repulsion and reduced adhesion As expected, adhesion of HPMC which is nonionic, was unaffected by pH of the hydration medium. Adhesion of HYAFF 11 p25, and HYAFF 11 p50 was not significantly different at the higher pH. The adhesion of dry films was greater (4203–6388 dyn/cm 2) than that of hyrdrated films. Adhesion of the dry films may be a result of wetting of the films and dehydration of the mucous layer by the films. The study of initial contact time showed a time dependent increase in force of adhesion after an initial equilibration time. The results indicate potential applicability of the hydrophilic HA esters as mucoadhesive polymers.