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Research Paper

Magnetic Assisted Transport of PLGA Nanoparticles Through a Human Round Window Membrane Model

[+] Author and Article Information
Xinsheng Gao

Hough Ear Institute, INTEGRIS Health, 3400 Northwest 56th Street, Oklahoma City, OK 73112xinsheng.gao@integris-health.com

Youdan Wang

Hough Ear Institute, INTEGRIS Health, 3400 Northwest 56th Street, Oklahoma City, OK 73112kwang@houghearinstitute.com

Kejian Chen

Hough Ear Institute, INTEGRIS Health, 3400 Northwest 56th Street, Oklahoma City, OK 73112kejian.chen@integris-health.com

Brian P. Grady

School of Chemical, Biological and Materials Engineering, University of Oklahoma, 100 East Boyd, Norman, OK 73019bpgrady@ou.edu

Kenneth J. Dormer

Department of Physiology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Boulevard, Oklahoma City, OK 73104kenneth-dormer@ouhsc.edu

Richard D. Kopke1

Hough Ear Institute, INTEGRIS Health, 3400 Northwest 56th Street, Oklahoma City, OK 73112rkopke@houghearinstitute.com

1

Corresponding author.

J. Nanotechnol. Eng. Med 1(3), 031010 (Aug 23, 2010) (6 pages) doi:10.1115/1.4002043 History: Received May 14, 2010; Revised June 10, 2010; Published August 23, 2010; Online August 23, 2010

The lack of an effective method for inner ear drug delivery is a clinical problem for the prevention and treatment of hearing loss. With technology advances in nanomedicine and the use of hydrogels, more drug delivery options are becoming available. This study tested the feasibility of using a tripartite layer round window membrane (RWM) model to evaluate the effectiveness of a magnetic assisted transport of poly(lactic-co-glycolic acid) (PLGA)/superparamagnetic iron oxide nanoparticles (SPIONs). A RWM model was constructed as a three-cell-layer model with epithelial cells cultured on both sides of a small intestinal submucosal (SIS) matrix with fibroblasts seeded within the matrix. PLGA encapsulated coumarin-6/SPION nanoparticles 100 nm in diameter were formulated by an oil-in-water emulsion/solvent evaporation method and pulled through the RWM model using permanent magnets with a flux density 0.410 T at the pole face. Independent variables such as external magnetic force and exposure time, composition of hyaluronic acid (HA) hydrogel suspending media, and particle characteristics including magnetic susceptibility were studied. Magnetic assisted transport of coumarin-6 labeled magnetic nanoparticles through the RWM inserts increased 2.1-fold in 1 h compared with the controls. HA hydrogel did prevent particle accumulation on the surface of RWM in a magnetic field but also impaired the mobility of these particles. Greater particle susceptibility or stronger external magnetic fields did not significantly improve the transmembrane transport. A RWM model was designed consisting of a SIS membrane and three co-cultured layers of cells, which was structurally and physically similar to the human. PLGA particles (100 nm) with encapsulated 15nm SPIONs were transported through this model with the assistance of an external magnet, allowing quantitative evaluation of prospective targeted drug delivery through the RWM via the assistance of a magnetic field.

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Copyright © 2010 by American Society of Mechanical Engineers
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Figures

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Figure 1

TEM images of coumarin labeled magnetic PLGA nanoparticles. Magnifications in A and B were 20,000× and 100,000×, respectively. The dark spots in B were SPIONs evenly spread inside the PLGA particles.

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Figure 2

The time course of the RWM MAT of CMNPs. The fluorescence intensity of coumarin-6 extracted from the magnet assisted transports and controls without magnetic flux was measured at 500 nm using an excitation wavelength of 430 nm. The significance of differences was compared within all control and MAT samples and also between control and MAT samples. The results were analyzed using Student's paired two-tailed t-tests. Results are expressed as means±SEM. Asterisks  ∗,  ∗∗, and  ∗∗∗ represent p<0.05, p<0.01, and p<0.001, respectively.

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Figure 3

Bar graphs of the RWM MAT of CMNPs suspended in hydrogel of different molecular weight. The transmembrane permeability data were shown for CMNPs suspended in 9 mg/ml hydrogels with MW 0.75 MDa, 0.96 MDa, and 1.47 MDa. The significance of differences between control and MAT samples was obtained by Student's paired two-tailed t-tests. Results are expressed as means±SEM. Asterisks  ∗ and  ∗∗ represent p<0.05 and p<0.01, respectively.

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Figure 4

Bar graphs of the RWM MAT of CMNPs suspended in serial dilutions of hydrogel. The results indicated the transmembrane permeability data for CMNPs suspended in 0.67 mg/ml, 2 mg/ml, and 6 mg/ml hydrogel (MW 0.75 MDa). The significance of differences between control and MAT samples was obtained by Student's paired two-tailed t-tests. Results are expressed as means±SEM. Asterisks  ∗∗ and  ∗∗∗ represent p<0.01 and p<0.001, respectively.

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Figure 5

RWM MAT of CMNPs with different magnetic susceptibilities. The bar graphs show the fluorescence intensity of coumarin-6 extracted from CMNPs synthesized with 5 mg/ml, 10 mg/ml, and 20 mg/ml magnetites, respectively. The significance of differences between control and MAT samples was obtained by Student's paired two-tailed t-tests. Results are expressed as means±SEM. Asterisks  ∗,  ∗∗, and  ∗∗∗ represent p<0.05, p<0.01, and p<0.001, respectively.

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Figure 6

RWM magnet assisted transport of CMNPs under different magnetic fluxes. The bar graphs show the fluorescence intensity of coumarin-6 extracted from the MAT samples and control samples without magnetic flux. The results were obtained under magnetic fluxes of 0.25 T, 0.41 T, and 1.0 T. The significance of differences between control and MAT samples was obtained by Student's paired two-tailed t-tests. Results are expressed as means±SEM. Asterisks  ∗∗ and  ∗∗∗ represent p<0.01 and p<0.001, respectively.

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