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

Autor: D. Ponraju, Satish Srinivas, Suresh K. Rayala, Vuttaradhi Veena Kumari, Akila Kesavan, P. Ilaiyaraja, Ganesh Venkatraman, Anita Ramesh, J. Sugin Lal, W. Sofi Beaula, C. Arunkumar, G. Anjana
Rok vydání: 2015
Předmět:
Pharmaceutical Science
Apoptosis
IC50
Mice
SCID
Pharmacology
dendrimer
S Phase
Random Allocation
Drug Delivery Systems
Trastuzumab
Acetamides
antineoplastic agent
Ovarian Neoplasms
pH
Chemistry
ovary cancer
General Medicine
polyamidoamine
unclassified drug
Absorption
Physiological
Tumor Burden
Drug delivery
Female
ovarian cancer cell line
Drug carrier
Biotechnology
medicine.drug
Dendrimers
lanthanum
in vitro study
Surface Properties
tumor regression
Drug Compounding
animal experiment
Antineoplastic Agents
antineoplastic activity
in vivo study
Excipients
Inhibitory Concentration 50
In vivo
Dendrimer
Cell Line
Tumor
medicine
SCID mouse
Animals
Humans
controlled study
human
S phase cell cycle checkpoint
mouse
Cisplatin
nonhuman
diglycolamic acid
animal model
human cell
drug targeting
Xenograft Model Antitumor Assays
tumor xenograft
In vitro
Targeted drug delivery
drug synthesis
Nanoparticles
Zdroj: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 96
ISSN: 1873-3441
Popis: 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. � 2015 Elsevier B.V. All rights reserved.
Databáze: OpenAIRE
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