Subcellular drug targeting, pharmacokinetics and bioavailability

Abstract

Effective treatment of diseases at the molecular level is possible by directing the drug substance (micromolecular, protein or peptide drugs, DNA, oligonucleotides, siRNA) with the aid of a specialized nanoparticulate carrier, for safe and effective transport to the specific site of action in the cytosol and its organelles including nuclear targeting. To achieve efficient cytosolic delivery of therapeutics or nuclear targeting, different drug delivery systems (DDS) have been developed (macromolecular drug conjugates, chemically or genetically modified proteins, and particulate drug carriers) capable of subcellular internalization overcoming the biological barriers, by passive targeting and especially by active targeting (receptor-targeted delivery). The success depends on the physicochemical nature of DDS, intracellular barriers that these systems need to overcome, the bioavailability of the bioactive drug, biodistribution, the intracellular pharmacokinetics and its influence on the pharmacodynamic effect. Models necessary for this purpose exist but they need to be more developed especially with quantitative treatments, after the development of the means of highlighting the evolution of the drug substance in biophase or at the level of the target cellular organelle by quantitative assays. It is expected that intracellularly targeted drug delivery approaches will be clinically useful using specialized DDSs belonging to the pharmaceutical nanotechnologies.

Biodistribution and Pharmacokinetics of Mad2 siRNA-loaded EGFR-Targeted Chitosan Nanoparticles in Cisplatin Sensitive and Resistant Lung Cancer Models

“…This might be ascribed to the small number of time points, which would not enable the characterization of a biphasic kinetics and a relevant elimination halflife. Overall, the addition of EGFR targeting peptide induced a significantly higher exposure to tumor tissue, which is in line with most published results [41,59,60].…”

<p>Intracellular Distribution of Lipids and Encapsulated Model Drugs from Cationic Liposomes with Different Uptake Pathways</p>

“… 4 – 6 The performance of such therapeutics, including drug delivery systems, is usually related mainly to their bioavailability and the efficacy at the target sites, and both these factors are strongly related to the pharmacokinetics. 7 , 8 …”

Drug Delivery Strategies for Antivirals against Hepatitis B Virus

“…Classes of drug targeting fall into two groups, namely active and passive targeting. Active targeting utilizes certain interactions at the target site, such as those of ligand–receptor and antigen–antibody binding [ 4 ], or in other cases, signals such as temperature or magnetic fields that can be applied externally. Passive targeting involves adjusting carrier systems’ physicochemical properties to that of the physiological and histological features of the target site.…”