Buccal Delivery of [D-Ala2, D-Leu5]Enkephalin Incorporated in Mucoadhesive Poly(acrylic acid) Hydrogels

The objectives of the current work is to understand the factors impacting the formulation and performance of a Carbopol mucoadhesive buccal delvery system for a model peptide drug, $[D-Ala{^2},\;D-Leu{^5}]$enkephalin (DADLE, Mw=569.7) with comparable chemical and enzymatic stability. Specifically, in vitro buccal DADLE delivery from the cross-linked poly(acrylic acid) (PAA) hydrogel system was characterized. In addition, the influences of several penetration enhancers on the ex vivo buccal absorption of DADLE were also studied. In this study, the PAA hydrogels generally swell to 100% of their original weight in the phosphate pH 7.4 buffer. The water penetration into the PAA hydrogel occurred based on a zero-order kinetics for the first 60 min and steadily decreased afterwards. From the release study, it can be seen that the initial DADLE release was so rapid and the rate of release of DADLE decreased as the time elapsed. The porcine buccal tissue was found to be permeable to DADLE with a flux value of $0.07%/cm{^2}/hr({\pm}0.01\;SD)$. From the ex vivo diffusion study, it was found that sodium taurodihydrofusidate showed a greater degree of enhancement compared to the phospholipids with an Enhancement Ratio (ER) of 8.7 compared to 2.7 and 1.9 for didecanoylphosphatidylcholine and lysophosphatidylcholine, respectively. The work encompassed within this paper has demonstrated the feasibility of using the PAA hydrogel delivery system with its good mucoadhesive properties for the buccal delivery of peptides.