Design and in vitro evaluation of a mucoadhesive oral delivery system for a model polypeptide antigen

A novel mucoadhesive drug carrier system has been generated which protects a model polypeptide antigen from degradation by the most abundant intestinal proteases. The enzyme inhibitors antipain, chymostatin and elastatinal, respectively, were covalently attached to the mucoadhesive polymer sodium carboxymethylcellulose (NaCMC) and the inhibitory efficacy of the resulting polymer-inhibitor conjugates was evaluated in vitro. When these inhibitor conjugates were combined with the thiolated polymer polycarbophil-cysteine (PCP-Cys), 95.8 ± 3.8% (mean ± SD, n = 3) of the incorporated model antigen ovalbumin (OVA) was protected from enzymatic degradation within 90 min incubation in the presence of an artificial intestinal fluid containing the pancreatic serine proteases trypsin, chymotrypsin and elastase. Replacing the CMC-inhibitor conjugates in the dosage form by unmodified CMC significantly reduced the protective effect to 78.8 = ± 4.7% (mean ± SD, n = 3), whereas incorporation of the model antigen in a CMC dosage form omitting PCP-Cys protected 72.5 ± 3.2% (mean ± SD, n = 3) of OVA from degradation within a 90 min incubation period. Further, the incorporation of PCP-Cys resulted in higher cohesiveness within the dosage form and controlled drug release of the antigen for a time period of more than 9 h. Results suggest that a delivery system combining thiolated polymer and polymer-inhibitor conjugates improves the metabolic stability of the model polypeptide antigen and may therefore be a useful tool for oral protein vaccination.