Dual Drug Conjugate Loaded Nanoparticles for the Treatment of Cancer

Author(s): Megha Shyam Matlapudi, Afrasim Moin, Raghavender Medishetti, K. Rajendra, Ashok M. Raichur, B.R. Prashantha Kumar.

Journal Name: Current Drug Delivery

Volume 12 , Issue 6 , 2015

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Abstract:

Two antineoplastic agents, Imatinib (IM) and 5-Fluorouracil (FU) were conjugated by hydrolysable linkers through an amide bond and entrapped in polymeric Human Serum Albumin (HSA) nanoparticles. The presence of dual drugs in a common carrier has the advantage of reaching the site of action simultaneously and acting at different phases of the cell cycle to arrest the growth of cancer cells before they develop chemoresistance. The study has demonstrated an enhanced anticancer activity of the conjugate, and conjugate loaded stealth HSA nanoparticles (NPs) in comparison to the free drug in A-549 human lung carcinoma cell line and Zebra fish embryos (Danio rerio). Hydrolysability of the conjugate has also been demonstrated with complete hydrolysis being observed after 12 h. In vivo pharmacodynamics study in terms of tumor volume and pharmacokinetics in mice for conjugate (IM-SC-FU) and conjugate loaded nanoparticles showed significant anti-cancer activity. The other parameters evaluated were particle size (86nm), Poly Dispersive Index (PDI) (0.209), zeta potential (-49mV), drug entrapment efficiency (96.73%) and drug loading efficiency (89%). Being in stealth mode gives the potential for the NPs to evade Reticulo-Endothelial system (RES), achieve passive targeting by Enhanced Permeation Retention (EPR) effect with controlled release of the therapeutic agent. As the conjugate cleaves into individual drugs in the tumor environment, this promises better suppression of cancer chemoresistance by delivering dual drugs with different modes of action at the same site, thereby synergistically inhibiting the growth of cancerous tissue.

Keywords: Cancer chemoresistance, controlled release, dual drug conjugates, polymeric nanoparticles, Zebrafish embryos (Danio rerio).

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Article Details

VOLUME: 12
ISSUE: 6
Year: 2015
Page: [782 - 794]
Pages: 13
DOI: 10.2174/1567201812666150507120452
Price: $58

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