Nanoparticle-based drug delivery: case studies for cancer and cardiovascular applications

Nanoparticles (NPs) comprised of nanoengineered complexes are providing new opportunities for enabling targeted delivery of a range of therapeutics and combinations. A range of functionalities can be included within a nanoparticle complex, including surface chemistry that allows attachment of cell-specific ligands for targeted delivery, surface coatings to increase circulation times for enhanced bioavailability, specific materials on the surface or in the nanoparticle core that enable storage of a therapeutic cargo until the target site is reached, and materials sensitive to local or remote actuation cues that allow controlled delivery of therapeutics to the target cells. However, despite the potential benefits of NPs as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of NP materials, as well as their size and shape. The need to validate each NP for safety and efficacy with each therapeutic compound or combination of therapeutics is an enormous challenge, which forces industry to focus mainly on those nanoparticle materials where data on safety and efficacy already exists, i.e., predominantly polymer NPs. However, the enhanced functionality affordable by inclusion of metallic materials as part of nanoengineered particles provides a wealth of new opportunity for innovation and new, more effective, and safer therapeutics for applications such as cancer and cardiovascular diseases, which require selective targeting of the therapeutic to maximize effectiveness while avoiding adverse effects on non-target tissues.     

Hepatic blood flow in acute myocardial ischemia

Hepatic blood flow was monitored in cats during myocardial ischemia (MI). Increased plasma CPK activity, the S-T segment of the electrocardiogram, and hepatic flow was reduced by 5 h to 40% of control. The results suggest that MI can influence organs distant from the original ischemic episode.     

Effect of suppression of endocrine or exocrine pancreatic function in hemorrhagic shock

Summary Somatostatin did not influence the pathologic consequences of hemorrhagic shock, but pancreatic duct ligation prevented the post-oligemic decline of arterial pressure and formation of toxic factors. These results indicate that pancreatic acinar cells release myocardial depressant factor and are important in the pathophysiology of shock.Supported in part by research grant No. HL-17745 from the National Heart, Lung and Blood Institute of the NIH.Acknowledgments. We gratefully acknowledge the expert technical assistance of Mary Ann Gaffney, Richard Levin and Kathleen Shupe during the course of these investigations. We also thank Dr William D. Cash of Ciba-Geigy Co., Ardsley, New York, for the supply of somatostatin.     

Effect of suppression of endocrine or exocrine pancreatic function in hemorrhagic shock.

Somatostatin did not influence the pathologic consequences of hemorrhagic shock, but pancreatic duct ligation prevented the post-oligemic decline of arterial pressure and formation of toxic factors. These results indicate that pancreatic acinar cells release myocardial depressant factor and are important in the pathophysiology of shock.     

Hepatic blood flow in acute myocardial ischemia

Summary Hepatic blood flow was monitored in cats during myocardial ischemia (MI). Increased plasma CPK activity, the S-T segment of the electrocardiogram, and hepatic flow was reduced by 5 h to 40% of control. The results suggest that MI can influence organs distant from the original ischemic episode.Supported in part by Research grant HL-17745 from the National Heart, Lung and Blood Institute of the National Institutes of Health.Acknowledgments. We gratefully acknowledge the expert technical assistance of Mary Ann Spath.