Ioxilan carbonate particles

Excerpt

Ioxilan carbonate particles (IX-C particles) are X-ray contrast agent preparations developed for contrast enhancement of the liver in computed tomography (CT) imaging (1-3). Water-soluble, intravenous ioxilan injection is commercially available as an X-ray contrast agent for excretory urography and contrast enhanced computed tomographic (CECT) imaging of the head and body. However, IX-C as insoluble particles is not commercially available.

X-ray imaging (planar and tomographic) techniques depend on tissue density differences that provide the image contrast produced by X-ray attenuation between the area of interest and surrounding tissues (4). Contrast enhancement (opacification) with use of contrast agents increases the degree of contrast and improves the differentiation of pathologic processes from normal tissues. Because iodine, an element of high atomic density, causes high attenuation of X-rays within the diagnostic energy spectrum, water-soluble and reasonably safe iodinated contrast agents in intravenous injectable forms have been developed for clinical applications (5, 6). Water-soluble, intravenous X-ray contrast agents are generally organic iodine compounds that contain one or more tri-iodinated benzene rings. When injected intravenously, they are largely distributed in the extracellular fluid space and excreted unchanged by the kidneys. Contrast enhancement of a region of interest depends on the route of administration, delivery of the agent to the area by blood flow, and the final iodine concentration in the region (7, 8). There are two basic types of these compounds: ionic and nonionic agents (9).

Rapid i.v. injection of water-soluble X-ray contrast agents can be performed with dynamic computed tomography to improve the detectability of liver lesions (1-3). However, there are many limitations associated with this approach. Particulate contrast media have also been developed for selective opacification of the liver. This approach is based on the fact that particles are effectively taken up by the phagocytic cells (Kupffer cells) of the reticuloendothelial system (RES). Several particulate contrast agents have been developed. These particulate contrast agents can be classified into three groups: 1) emulsion of liposoluble oil; 2) encapsulation of water-soluble X-ray contrast agents in liposomes or polymeric microspheres; and 3) the lipophilic prodrugs derived from water-soluble contrast agents (1, 10). As a low-osmolar nonionic monomer, ioxilan was developed in an effort to increase the safety and tolerance of X-ray contrast agents (11, 12). The development of ioxilan was based on the belief that the introduction of a double methylene as a hydrophobic region and masking it with a hydrophilic hydroxyl group could lower the osmolality without adversely affecting the biological tolerance (13). Li et al. (1) prepared a biodegradable IX-C particle preparation based on the cyclic carbonate of ioxilan. IX-C particles serve as the prodrug of ioxilan that is targeted to the RES phagocytic cells. It is expected that IX-C particles are degraded inside the phagocytic cells to release the original nonionic, water-soluble ioxilan.