Pharmaceutica Analytica Acta

Development of ligand-mediated drug delivery systems for cancer targeted imaging and therapy

5^th International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems

March 16-18, 2015 Crowne Plaza, Dubai, UAE

Han-Chung Wu1, Chien-Hsun Wu1, Tann-Long Su1 and Hsing-Pang Hsieh2

Scientific Tracks Abstracts: Pharm Anal Acta

Abstract:

Lack of tumor specificity remains a major problem for chemotherapies in which side effects prevent the delivery of the drug dosages needed to eliminate the majority of cancer cells. Recently, we developed phage display methods to identify several novel peptides and human single chain variable fragment (scFv) antibodies that bind specifically to the plasma membrane of cancer cells. In an effort to develop targeting drug delivery systems, we used peptide-linked liposomes that carried doxorubicin to treat severe combined immunodeficiency (SCID) mice bearing human tumor xenografts. The peptidefunctionalised liposomes were found to have an enhanced anti-tumor effect and reduced toxicity. Combination treatment of peptide-mediated targeting liposomes was able to completely eradicate tumors in three-sixth of the total number of tumorbearing mice without any signs of recurrence. Targeting liposomes improved the therapeutic index by enhancing therapeutic efficacy, reducing side effects, and increasing the survival rate of tumor-bearing mice in orthotopic animal model. The tumor site fluorescent intensity in the mice treated with targeting peptide-linked quantum dots showed higher tumor uptake and increased tumor-normal tissue ratios. In addition, in vivo imaging by scFv-conjugated quantum dots clearly demonstrated the potential clinical use of the scFv in tumor targeting and imaging. Ligand-conjugated liposomes enhance pharmacokinetic and pharmacodynamic properties, improve efficacy and safety profiles, and allows for controlled biodistribution and drug release. Our study indicates that peptide- or scFv-mediated drug delivery systems show great promise for their applications in tumortargeted drug delivery and imaging.

Biography :

Wu is currently a Professor and the Vice Director of the Institute of Cellular and Organismic Biology at Academia Sinica. He is also a Professor at the College of Medicine of the National Taiwan University. His research interest focuses on the development of targeting drug delivery systems for cancer therapy and targeting imaging. He has also developed phage display and affinity maturation methods to generate of fully human monoclonal antibodies for treatment of human diseases. Wu is actively involved in basic and translational research in the areas of oncology and has received numerous awards.