Iron Oxide Nanoparticles for Sustained Delivery of Anticancer Agents

Iron Oxide Nanoparticles for Sustained Delivery of Anticancer Agents
By: Tapan K. Jain, Marco A. Morales, Sanjeeb K. Sahoo, Diandra L. Leslie-Pelecky, and Vinod Labhasetwar - Department of Pharmaceutical Sciences, College of Pharmacy, Nebraska Medical Center, Omaha, Nebraska 68198-6025, Department of Physics & Astronomy and Center for Materials Research & Analysis, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0111, and Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198-4525
Web Release Date: April 21, 2005
ACS Publications
Abstract:
We have developed a novel water-dispersible oleic acid (OA)-Pluronic-coated iron oxide magnetic nanoparticle formulation that can be loaded easily with high doses of water-insoluble anticancer agents. Drug partitions into the OA shell surrounding iron oxide nanoparticles, and the Pluronic that anchors at the OA-water interface confers aqueous dispersity to the formulation. Neither the formulation components nor the drug loading affected the magnetic properties of the core iron oxide nanoparticles. Sustained release of the incorporated drug is observed over 2 weeks under in vitro conditions. The nanoparticles further demonstrated sustained intracellular drug retention relative to drug in solution and a dose-dependent antiproliferative effect in breast and prostate cancer cell lines. This nanoparticle formulation can be used as a universal drug carrier system for systemic administration of water-insoluble drugs while simultaneously allowing magnetic targeting and/or imaging.
Synthesis of Magnetic Nanoparticles. Aqueous solutions of 0.1 M Fe(III) (30 mL) and 0.1 M Fe(II) (15 mL) were mixed, and 3 mL of 5 M ammonia solution was added dropwise over 1 min with stirring on a magnetic stir plate. The stirring continued for 20 min under a nitrogen-gas atmosphere. The particles obtained were washed 3 times using ultracentrifugation (30000 rpm for 20 min at 10 C) with nitrogen purged water. The iron oxide nanoparticle yield, determined by weighing of the lyophilized sample of the preparation, was 344 mg.
Formulations of Magnetic Nanoparticles. Formulations of iron oxide nanoparticles were developed, first by optimizing the amount of OA required to coat iron oxide nanoparticles completely, and then by optimizing the amount of Pluronic required to form an aqueous dispersion of OA-coated nanoparticles. To study the effect of OA, formulations with different weight ratios of OA to iron oxide nanoparticles were prepared. For this purpose, OA was added (6-250 mg corresponding to 1.7 wt % to 41.0 wt % of the total formulation weight, i.e., iron oxide nanoparticles plus OA) to the above solution of Fe(III) and Fe(II) following the addition of ammonia solution. The formulations were heated to 80 C while being stirred for 30 min to evaporate the ammonia, and then cooled to room temperature. The black precipitate thus obtained was washed twice with 15 mL of water; the excess OA formed an emulsion as apparent from the turbid nature of the supernatant. The precipitate was lyophilized for 2 days at -60 C and 7 mHg vacuum (LYPHLOCK 12 LABCONCO, Kansas City, MO).
X-ray Diffraction (XRD). The XRD analysis of lyophilized samples of OA-coated iron oxide nanoparticles was carried out using a Rigaku D-Max/B horizontal diffractometer with Bragg-Brentano parafocusing geometry (Rigaku, The Woodlands, TX). The equipment uses a Copper target X-ray tube with Cu K radiation. The parameters chosen for the measurement were 2 steps of 0.02, 6 s of counting time per step, and 2 range from 20 to 80. Approximately 15 mg of lyophilized sample was sprinkled onto a low-background quartz XRD holder coated with a thin layer of silicone grease to retain the sample.
Note: Please visit the website to view this report in its entirety.