Systemic and Biophase Bioavailability and Pharmacokinetics of Nanoparticulate Drug Delivery Systems

Sorin      Emilian Leucuta

Abstract

The development of the vectorized delivery systems combining advantages of the colloidal carriers, with active targeting to the receptors sites suggests that nanoparticles have a considerable potential for treatment after biophase internalization and pharmacokinetics, as for example gene therapy. Two major mechanisms can be distinguished for addressing the desired sites for drug release: (i) passive and (ii) active targeting. Examples of passive targeting were presented: organ targeting by the Enhanced Permeability and Retention (EPR) effect; targeting the mononuclear phagocitic system; organ targeting by chemoembolization or local (organ) administration;sterical stabilization of nanoparticles (PEGylation). A strategy that could allow active targeting involves the surface functionalization of drug carriers with ligands that are selectively recognized by receptors on the surface of the cells of interest. The source for biophase bioavailability can be the systemic bioavailability following common routes of adminstration (generally for systemic delivery of medicines), or directly the site specific biophase bioavailability for the formulations capable of cellular or nuclear drug internalization where the drug release only will take place (for nanoparticulate drug delivery systems, DDS). Once the pharmaceutical nanosystem was internalized, begins the release of the active moiety by different mechanisms, as for example the escape from endosome, or biodegradation of the polymer carrier or liberation of the active peptide or gene from a biological construct in the nucleus, etc. The presentation will discusses the pharmacokinetics of drugs after systemic administration but especially the biophase bioavailability and pharmacokinetics after the administration of biotechnology origin of therapeutic proteins like monoclonal antibodies, gene transfer products, plasmid DNAs, nucleotides, antisense oligonucleotides (AODNs) or small interfering RNAs (siRNA).

Keywords: Bioavailability, drug delivery systems, internalization, intracellular, intranuclear, nanoparticles, pharmacokinetics, targeting