ABSTRACT
Gene and small interference RNA (siRNA) therapy has tremendous potential for the treatm ent of numerous diseases, including cancer as well as genetic, metabolic, and inflammatory diseases. Realization of this potential has been primarily halted by challenges associated with the delivery of these materials at desired biological target sites. Oral administration of nucleic acids is even more challenging since additional physiological barriers of the GI tract which rapidly degrade administered naked nucleic acids have to be bypassed. In order to protect nucleic acids from rapid degradation in the GI tract, a delivery vector is needed which can adequately protect the encapsulated payload, along with capability to facilitate uptake and in vivo expression of delivered material by desired target cells. In
this chapter, we will discuss polyester-based multicompartmental systems for oral gene and siRNA delivery developed in our laboratories. A solid-in-solid multicompartmental system referred to as nanoparticle-in-microsphere oral system (NiMOS) consisting of type B gelatin nanoparticles encapsulated within poly(c-caprolactone) (PCL)-based microsphere was developed for intestinal nucleic acid delivery via the oral route. This system was evaluated for local anti-inflammatory nucleic acid therapy for the treatm ent of inflammatory bowel disease (IBD) in colitis bearing mice. Results obtained from these studies demonstrate utility of multicompartmental systems for overcoming physiological barriers and enabling site-specific release of encapsulated material for alleviating disease symptoms.
