Chapter 3 - In vivo studies: toxicity and biodistribution of nanocarriers in organisms

Abstract

Drug development today faces challenges with poor pharmacokinetic properties of drugs, leading to low bioavailability and hence, low pharmacodynamic efficacy of drugs. This has remained a major obstacle behind clinical translation of many potential drug candidates. Targeted drug delivery has gained substantial limelight in this regard. It has improved pharmacokinetic properties of drugs and enhanced therapeutic efficacy. The concept of targeted delivery is incomplete without nanotechnology which is the current focus of the scientific world. Nanotechnology has extended its roots to major scientific areas like imaging, diagnostics, and drug delivery. Their increasing employment is attributed to their dominant optical, electric, and magnetic properties imparted due to their exceptionally small size. Their ability to provide long drug shelf life, a highly stable environment, high carrier capacity, convenient loading of both hydrophilic and hydrophobic substances, tunable surface chemistry and controlled drug release amalgamated with augmented biodistribution and pharmacokinetic drug profile is highly commendable in this regard. A variety of nanocarriers such as carbon nanotubes, metal and polymeric nanoparticles, polymeric micelles, liposomes, dendrimers, dendriplexes, etc. are employed in different fields owing to their variable physicochemical properties. However, the vast utility of nanocarriers in the day-to-day scientific world has raised many objections on their safety profile. Many of them have been reported to undergo acute and chronic accumulation in various organs which leads to homeostatic disturbances and subsequent associated vital organ toxicities. Although the distribution pattern is different for different types of nanocarriers, the major uptake is reported in RES (reticuloendothelial system) organs like liver and spleen. Size dependent toxicity is reported for nanoparticles. Conversely, dendrimers, dendriplexes, and liposomes have been reported to produce minimal toxicity and thus, are preferred over their other nano counterparts. Toxicities can be altered by varying routes of administration, size and surface functionalities of nanocarriers which are discussed in detail here. The current book chapter provides insights into different types of nanocarriers, their applications, and presents a detailed discussion on their biodistribution profiling and different organ toxicities.