Preparation of gelatin hydrogels incorporating small interfering RNA for the controlled release

Abstract

The objective of this study is to design biodegradable hydrogels of gelatin for the controlled release of bioactive small interfering RNA (siRNA). Gelatin was cationized by chemically introducing ethylene diamine into the carboxyl groups in different conditions to obtain cationized gelatins (CGs). The CG was mixed with siRNA at various mixing ratios of amino groups of gelatin to the phosphate groups of siRNA in aqueous solution to form the siRNA–CGnano-complex. Gelatin together with the complex of siRNA and CG was chemically crosslinked to prepare the gelatin hydrogel incorporating the complex. The hydrogel incorporating the siRNA–CG complex was hardly degraded in phosphate-buffered saline solution (PBS) at 37°C and did not release the siRNA complex after initial siRNA release. When placed in PBS containing collagenase, the hydrogel was enzymatically degraded to release the siRNA complex. In this release system, the siRNA was released as a result of hydrogel degradation. The siRNA released showed an activity to specifically suppress the expression of the corresponding gene. The hydrogel is promising to release siRNA and also elicit biological activity for a longer time.

Keywords::

• Gelatin hydrogel
• controlled release
• siRNA
• gene delivery