Pharmacokinetic Modelling to Study the Biodistribution of Nanoparticles

Complex Factors and Challenges that Affect the Pharmacology, Safety and Efficacy of Nanocarrier Drug Delivery Systems

“…Absorption can only be measured with medications administered orally or subcutaneously (SQ). The extravascularly administered drug will enter the absorption phase after the administration and then crosses over membranes to reach the systemic circulation [ 16 , 17 ]. However, NPs face numerous physiological barriers with all types of the route of administrations (oral, intravenous [IV], intramuscular [IM], and SQ) [ 18 ].…”

“…The distribution between small-molecule drugs and NPs are also different, primarily due to the properties and characteristics of the carrier transporting the cytotoxic payload. Small-molecule drugs usually have a high distribution because they distribute to organs and tissues much easier than NPs and take advantage of various membrane transporters (e.g., OCT1, PgP) to cross from the blood circulation to the site of action [ 17 , 22 , 23 ]. Unlike small-molecule drugs, NPs have limited distribution due to vasculature and interstitial space within tissues, and cannot be diffused easily from the central to the peripheral compartment [ 16 , 18 ].…”

“…While many factors responsible for the process have been identified, the mononuclear phagocyte system (MPS), which is part of the innate immune system (IIS), is believed to contribute the most to this effect. The uptake and elimination of NPs are done by numerous MPS cells such as circulating phagocytes (e.g., monocytes, dendritic cells) or tissue residing phagocytes (e.g., Kupffer cells in the liver) [ 16 , 17 , 18 , 23 ]. While this interaction has been documented previously, questions still exist attributed to inter-patient differences in this MPS component, and therefore, it is important that sampling should be taken into consideration.…”