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

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 96; pp. 255 - 263
• Main Authors: Kesavan, Akila, Ilaiyaraja, P., Sofi Beaula, W., Veena Kumari, Vuttaradhi, Sugin Lal, J., Arunkumar, C., Anjana, G., Srinivas, Satish, Ramesh, Anita, Rayala, Suresh Kumar, Ponraju, D., Venkatraman, Ganesh
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2015
• Subjects: Absorption, Physiological; Acetamides - chemistry; Animals; Anti-tumor activity; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Apoptosis - drug effects; Cell Line, Tumor; Cisplatin; Cisplatin - administration & dosage; Cisplatin - metabolism; Cisplatin - pharmacology; Cisplatin - therapeutic use; Dendrimers - chemistry; Diglycolamic acid; Drug Compounding; Drug Delivery Systems; Excipients - chemistry; Female; Herceptin; Humans; Inhibitory Concentration 50; Mice, SCID; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; PAMAM dendrimers; Random Allocation; S Phase - drug effects; Surface Properties; Targeted drug delivery; Trastuzumab - chemistry; Tumor Burden - drug effects; Xenograft Model Antitumor Assays; Herceptin; PAMAM dendrimers; Targeted drug delivery; Anti-tumor activity; Diglycolamic acid; Cisplatin; Apoptosis
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2015.08.001

[Display omitted] 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.