The influence of fumaric anhydride on bioadhesive polymer compositions

摘要

Bioadhesive polymers are useful as drug delivery systems designed to adhere to the gastrointestinal lumen. The interaction between polymer ad mucosal tissue influences residence time of the polymeric device and greatly affects the bioavailability of encapsulated drug. Poly(fumaric-co-sebacic anhydride) [P(FA:SA)] demonstrated impressive results in a variety of in vitro and in vivo experiments designed to test bioadhesion of microspheres. Among different molar ratios of P(FA:SA), adhesive measurements increased with increasing fumaric acid (FA) content. Using a modified microbalance technique, P(FA;SA) 10:90 yielded a tensile work measurement of 82.99+-12.76 nJ (mean+-SEM) while that for P(FA:SA)70:30 was 453.23+-47.73 nJ. A low molecular weight substance, fumaric anhydride prepolymer (FAPP), the oligomer form of fumaric acid, was incorporated into the microspheres and greatly increased the bioadhesive properties of P(FA:SA) as well as those of the relatively non-bioadhesive polymer poly(caprolactone) (PCL). Tensile work of P(FA:SA)20:80 was 32.95+-5.42 nJ, and P(FA:SA)20:80 with 25percent FAPP yielded a tensile work measurement of 556.28+-113.12 nJ. Adhesion testing with PCL yielded a tensile work measurement of 7.93+-1.84 nJ, while that for PCL with 25percent FAPP was 1629.54+-307.55 nJ. The effect of FA on drug delivery was evaluated in vitro using the P(FA:SA):FAPP blend with the everted intestinal sac technique. A low molecular weight drug (sodium salicylate) encapsulated in P(FA:SA)20:80 passed through the everted intestinal lumen to the interior of the sac to yield a concentration of 11.17+-0.93 mg/dL, and drug encapsulated in P(FA:SA)20:80 with 10percent FAPP yielded a concentration of 16.25+-1.68 mg/dL (P<=0.05). Unencapsulated drug passed through the intestinal lumen to yield a concentration of 8.09+-0.36 mg/dL. These experiments demonstrate that fumaric anhydride could be a very important component in bioadhesive polymer systems.