Chapter 3 - Passive targeting

Abstract

Cancer is a leading cause of death globally. For the effectual treatment of cancer, it is crucial to advance our knowledge of the pathophysiology of cancer, discover novel anti-cancer agents, and expand new biomedical technology. A large number of possible barriers exist in the efficient delivery of small-sized drugs to solid tumors. After intravenous administration, many small-sized chemotherapeutic medicines have a larger volume of distribution, which is usually related to a narrow therapeutic index that is attributable to their elevated level of toxic effects in healthy tissues. A nanoparticle-based drug for targeting cancer is one of the auspicious advances to conquer the lack of tissue specificity associated with common chemotherapeutic drugs. Accordingly, the overall objectives are to lengthen a patient's lifespan, avoid recurrence of the cancer, and concurrently lessen the toxic effects of chemotherapeutic drugs. A range of approaches have been investigated for the nanoparticle mediated targeting of drugs. Among them, a passive drug-targeting approach has been the most commonly explored, and much preclinical experimentation has provided insight into its soundness. This approach is in accordance with the abnormality of tumor vasculatures, allowing nanoparticles entry to tumors while avoiding distribution into healthy tissues. Thus, a passive drug targeting approach facilitates the advancement of a targeted nano-carrier structure, loaded with chemotherapeutic agents, for an improved effective profile with negligible toxic effects. Passive targeting facilitates deposition of nanostructures within the tumor microenvironment, owing to distinctive characteristics inherent to the tumor milieu, not normally present in healthy tissues. The delivery of nanoparticles is determined by factors associated with the tumor microvasculature, in addition to factors inherent to the nanoparticle itself, such as size, shape and surface charge. Targeting strategies have taken a step further to enhance the selective uptake of nanoparticles into the tumor cells. Bio-recognition molecules have been attached to the surface of the nanostructures to target specific markers that are overexpressed by the neoplastic cells. These strategies have been awarded the appellation ‘active targeting’, which exhibits a higher specificity and efficacy in achieving the desired goal. In this chapter, we present passive targeting strategy and effective factors on that.