Tumor targeting using polyamidoamine dendrimer-cisplatin nanoparticles functionalized with diglycolamic acid and herceptin.

Abstract

Polymer mediated drug delivery system represents a novel promising platform for tumor-targeting with reduced systemic side effects and improved chemotherapeutical efficacy. In this study, we report the preparation and characterization of herceptin targeted, diglycolamic acid (DGA) functionalized polyamidoamine (PAMAM) dendrimer as a potent drug carrier for cisplatin. DGA dendrimers carrying cisplatin demonstrated enhanced anticancer activity when targeted with herceptin. In vitro cell line studies with herceptin-DGA-G4-cisplatin in HER-2 +ve and HER-2 -ve human ovarian cancer cell lines showed that these nanoparticles possessed remarkable features such as lower IC50 value, improved S-phase arrest, and enhanced apoptosis due to increased cellular uptake and accumulation than the untargeted DGA-G4-cisplatin and free cisplatin. Furthermore, in vivo results in SCID mice bearing SKOV-3 tumor xenografts, herceptin-DGA-G4-cisplatin, appeared to be more effective in inducing tumor regression as compared to free cisplatin. Collectively, these results indicate that herceptin targeted DGA functionalized PAMAM-cisplatin conjugates serve as better anti-tumor agents than individual therapeutic agents.

• Authors: Akila Kesavan, P Ilaiyaraja, W Sofi Beaula, Vuttaradhi Veena Kumari, J Sugin Lal, C Arunkumar, G Anjana, Satish Srinivas, Anita Ramesh, Suresh Kumar Rayala, D Ponraju, Ganesh Venkatraman
• Journal: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V (Eur J Pharm Biopharm) Vol. 96 Pg. 255-63 (Oct 2015) ISSN: 1873-3441 [Electronic] Netherlands
• PMID: 26277659 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Acetamides
• Antineoplastic Agents
• Dendrimers
• Excipients
• PAMAM Starburst
• Trastuzumab
• Cisplatin

Topics

• Absorption, Physiological
• Acetamides (chemistry)
• Animals
• Antineoplastic Agents (administration & dosage, metabolism, pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cisplatin (administration & dosage, metabolism, pharmacology, therapeutic use)
• Dendrimers (chemistry)
• Drug Compounding
• Drug Delivery Systems
• Excipients (chemistry)
• Female
• Humans
• Inhibitory Concentration 50
• Mice, SCID
• Nanoparticles (chemistry, ultrastructure)
• Ovarian Neoplasms (drug therapy, metabolism)
• Random Allocation
• S Phase (drug effects)
• Surface Properties
• Trastuzumab (chemistry)
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays