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S. E. Leucuta. Subcellular drug targeting, pharmacokinetics and bioavailability. . J Drug Target. 2014 Feb; 22(2):95-115. doi: 10. 3109/1061186X. 2013. 848453. Epub 2013 Nov 5. , 2014.

Abstract: 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.

Keywords: Bioavailability, biophase, cell internalization, drug delivery systems (DDS), drug targets, nuclear internalization, pharmacokinetics, pharmacodynamics, subcellular targeting, target cell organelles

Posted by Sorin Emilian Leucuşa

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