Folic acid conjugated magnetic drug delivery system for controlled release of doxorubicin
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RESEARCH PAPER
Folic acid conjugated magnetic drug delivery system for controlled release of doxorubicin Nidhi Andhariya • Ramesh Upadhyay • Rasbindu Mehta • Bhupendra Chudasama
Received: 9 September 2012 / Accepted: 2 January 2013 Ó Springer Science+Business Media Dordrecht 2013
Abstract Targeting tumors by means of their vascular endothelium is a promising strategy, which utilizes targets that are easily accessible, stable, and do not develop resistance against therapeutic agents. Folate receptor is a highly specific tumor marker, frequently over expressed in cancer tumors. In the present study, an active drug delivery system, which can effectively target cancer cells by means of folate receptor-mediated endocytosis, have ability to escape from opsonization and capability of magnetic targeting to withstand the drag force of the body fluid have been designed and synthesized. The core of the drug delivery system is of mono-domain magnetic particles of magnetite. Magnetite nanoparticles are shielded with PEG, which prevents their phagocytosis by reticuloendothelial system. These PEG shielded magnetite nanoparticles are further decorated with an N. Andhariya (&) B. Chudasama (&) School of Physics and Materials Science, Thapar University, Patiala 147 004, India e-mail: [email protected] B. Chudasama e-mail: [email protected] N. Andhariya R. Mehta Department of Physics, Maharaja Krishnakumarsinhji Bhavnagar University, Bhavnagar 364 022, India R. Upadhyay P.D. Patel Institute of Applied Sciences, Charotar University of Science and Technology, Changa 388 421, India
antitumor receptor—folic acid and loaded with an antineoplastic agent doxorubicin. An in vitro drug loading and release kinetics study reveals that the drug delivery system can take 52 % of drug load and can release doxorubicin over a sustained period of 7 days. The control and sustained release over a period of several days may find its practical utilities in chemotherapy where frequent dosing is not possible. Keywords Magnetic drug targeting Active delivery Doxorubicin Folate receptor Magnetite
Introduction Drug targeting is defined as selective drug delivery to specific physiological sites, organs, tissues, or cells where a drug’s pharmacological activities are required (Yokoyama and Okano 1996; Takakura et al. 1999). Drug-targeting technologies have been applied to drugs whose clinical use is difficult, as exemplified by anticancer drugs. In principle, a drug distributes uniformly in the whole body when it is injected in the blood, and the drug that is distributed at sites other than the therapeutic sites may cause toxic side effects. By increasing delivery to the therapeutic sites and reducing the delivery to unwanted regions, an improved therapeutic index can be obtained with enhanced and reduced drug action at the therapeutic and the unwanted sites, respectively.
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The rapid growth of cancer tumors confers them with fenestrated vasculature and poor lymphatic drainage, resulting in an enhanced permeability
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