Design of pH-Responsive Biomaterials to Enable the Oral Route of Hematological Factor IX

Abstract

The oral administration of hematological factor IX (FIX) can offer a convenient prophylactic treatment for hemophilia B patients. pH-Responsive hydrogels based on poly(methacrylic acid)-grafted-poly(ethylene glycol) (P(MAA-g-EG)) have been engineered as delivery vehicles for FIX. In oral delivery, such hydrogel carriers protected FIX from the gastric environment and released it under intestinal conditions as demonstrated by evaluation of the loading and release of FIX. Tailoring of the hydrogel networks improved the loading of FIX within the microcarriers, which is critical for minimizing protein degradation. Optimizing the loading conditions by increasing the incubation time and using a reduced ionic strength buffer further improved the delivery potential of the microcarriers. The presence of the microcarriers significantly enhanced the oral absorption of FIX in vitro. As shown in this work, P(MAA-g-EG) microcarriers are promising candidates for the oral delivery of FIX.