Nanomedicine and Drug Delivery

Biography

Biography: Aleksander F. Sikorski

Abstract

Statement of the Problem: Nanoparticle-based drug formulations are expected to be more efficient and less toxic than conventional drug formulations. This is indeed true in case of the most widely used nanoparticles including liposomes, micelles, dendrim­ers, nanotubes, and polymers. Moreover, most of the nanoparticle-based drug formulations offer a possibility of targeting the drug-loaded vehicles. Such strategy in case of anticancer drugs promises to be a hopeful strategy that allows to reduce toxicity and minimize adverse side effects. Targeting exploits the high affinity of cell-surface-targeted ligands, for specific retention and uptake by the targeted diseased cells.

Methodology & Theoretical Orientation: In this short review we would like to point to the application of liposomes as a versatile anticancer therapeutic carrier which can be targeted with antibodies directed against specific surface markers of cancer cells. Long-circulating liposomes containing PEG-PE and chemically activated PEG (e.g. maleimide derivative) may be considered as “Lego blocks”. Combining them with other components (i.e. drugs and surface-exposed molecules) in different configurations opens up multiple possibilities for different formulations of targeted anticancer drugs. They can be directed to specific tumor cells via targeting ligand(s) which could be attached covalently to the surface of liposomes. Prominent, relatively easy to apply as targeting agents are therapeutic antibodies already available on the market. Such liposomes may contain actively or passively encapsulated therapeutics of various nature.

Conclusion & Significance: Two types of such nanocarriers were developed in our laboratory. One consists of BCL-2 antisense oligodeoxynucleotide complexed with cationic lipid or polyethyleneimine with anti CD20 antibody and the other is based on simvastatin carrying liposomes targeted with anti HER2 antibody. The former type of formulations fulfill criteria of size, stability, specificity and high efficacy against specific type of cancer cells without obvious side effects in both in vitro and in vivo studies. Liposomal formulation of simvastatin targeted with HER2 antibody proves promising vehicle to deliver relatively high amounts of simvastatin to HER2 overexpressing cells.