Lipiodol-loaded poly(oxyethylene)--poly(oxypropylene)--poly(oxyethylene) triblock copolymers/polyethylene glycol-nanoparticles

Lipiodol-loaded poly(oxyethylene)--poly(oxypropylene)-poly(oxyethylene) (PEO-PPO-PEO) triblock copolymers/polyethylene glycol (PEG)-nanoparticles (LPNCs) are X-ray contrast agent preparations developed for contrast enhancement in computed tomography (CT) imaging (1). Lipiodol is an iodized poppy seed oil (ethyl esters of iodized fatty acids of poppy seed oil with 480 mg of iodine/ml) that can be used as an X-ray contrast agent for lymphography and hysterosalpingography. It is commercially available for investigation but has not been approved by the United States Food and Drug Administration for clinical use in humans. X-ray imaging techniques (planar and CT) depend on tissue density differences that provide the image contrast produced by X-ray attenuation between the area of interest and surrounding tissues (2). Contrast enhancement (opacification) with the use of contrast agents increases the degree of contrast and improves the differentiation of pathological processes from normal tissues. Because iodine, an element with 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 (3, 4). 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 (5, 6). Intravenous injection of water-soluble X-ray contrast agents can be performed in conjunction with dynamic CT to improve the detectability of tissue pathologies (4, 5, 7). However, there are many limitations associated with this approach because of their nonspecificity and rapid extravasation from the circulation. Nanoparticle contrast media have also been developed to improve the circulation time and target specificity of contrast agents (8, 9). One possible approach involves encapsulation of water-soluble or -insoluble X-ray contrast agents in various nanoparticle carriers (1, 8, 10, 11). Although these nanoparticle carriers are naturally taken up by the reticuloendothelial system, they can be modified with specific targeting moieties to increase the affinity of nanoparticles for target tissues, organs, and cells (1, 11-13). Among the nanoparticle carriers, PEO-PPO-PEO triblock copolymers are macromolecular surfactants composed of poly(oxyethylene)--poly(oxypropylene)--poly(oxyethylene) (Pluronic or Poloxamer series). Through hydrophobic interactions between the PPO blocks, these surfactants undergo self-assembly into spherical micelles in aqueous solution above a critical temperature (14). These nanoparticles can expand and shrink rapidly in response to temperature changes (15-17). Bae et al. (14) prepared LPNCs with the use of a new class of PEO-PPO-PEO/PEG nanoparticles to encapsulate lipiodol oil. LPNCs have an inner hydrophobic oil phase stabilized by a covalently cross-linked PEO-PPO-PEO/PEG shell layer. Kong et al. (1) reported that this LPNC nanoparticle preparation has effective X-ray attenuation properties and longer circulation time than those of conventional water-soluble contrast agents. The authors suggested that the conjugation of an appropriate targeting moiety might lead to the active targeting of LPNCs to a specific tissue or organ.