Research Paper

Incorporation, Release, and Effectiveness of Dexamethasone in Poly(Lactic-Co-Glycolic Acid) Nanoparticles for Inner Ear Drug Delivery

[+] Author and Article Information
Youdan Wang, Xinsheng Gao, Satish Kuriyavar, Kejian Chen

 Hough Ear Institute, 3400 Northwest 56th Street, Oklahoma City, OK 73112

David Bourne

Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, 1110 North Stonewall, Oklahoma City, OK 73117

Brian Grady

School of Chemical, Biological and Materials Engineering, University of Oklahoma, 100 East Boyd, Norman, OK 73069

Kenneth Dormer

Department of Physiology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Boulevard, Oklahoma City, OK 73104

Richard D. Kopke1

 Hough Ear Institute, 3400 Northwest 56th Street, Oklahoma City, OK 73112rkopke@houghear.org


Corresponding author.

J. Nanotechnol. Eng. Med 2(1), 011013 (Feb 10, 2011) (7 pages) doi:10.1115/1.4002928 History: Received September 15, 2010; Revised September 27, 2010; Published February 10, 2011; Online February 10, 2011

Poly (D ,L -lactide-co-glycolide) (PLGA) particles have been widely used as drug delivery carriers for a variety of payloads. Three forms of dexamethasone (DEX), namely, acetate, base, and phosphate, were incorporated into a PLGA matrix. First, we compared the drug loading efficiency and release kinetics of drug-loaded PLGA particles. Dexamethasone acetate (DEX-Ac) loaded particles exhibited a higher loading efficiency and a more linear release profile of drug as compared with the other forms of DEX particles. Also, we coincorporated oleic acid-coated superparamagnetic iron oxide nanoparticles (SPION) with DEX-Ac into PLGA submicron particles. No differences in size, zeta potential, drug loading, or release kinetics were found between particles prepared with and without SPION. Additionally, particles were applied to an in vitro cochlear, organotypic culture. DEX-Ac PLGA nanoparticles showed a protective effect against 4-hydroxynonenal induced hair cell damage. These results suggest a promising method for inner ear magnetic targeted treatment.

Copyright © 2011 by American Society of Mechanical Engineers
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Figure 1

(a) TEM images, (b) DEX-Ac/SPION PLGA nanoparticles, and (c) DEX-Ac PLGA nanoparticles. Magnifications in (a)–(c) were 40,000X, 100,000X, and 200,00X, respectively. The typical particle size ranged from 50 nm to 120 nm.

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Figure 2

Sustained release of DEX-P and DEX-B from particles. These are from the representative runs. Although the total amount of DEX release varied, the very high burst release and the short time required for all samples to reach a plateau were consistent for these encapsulated drugs.

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Figure 3

Sustained release of DEX-Ac from particles. The error bars were calculated from five duplicate runs. For the nanoparticles containing SPIONs, two duplicate runs were done, which is why there are two data points for each time increment. Release profiles for DEX-Ac and DEX-Ac/SPION nanoparticles are almost identical and showed that the incorporation of magnetite did not significantly affect the release kinetics of the drug. Both types of nanoparticles achieved sustained release over 2 weeks. The total amount of drugs encapsulated in this particle was 0.63 mg/mg particle for the non-SPION containing particle and 0.61 mg/mg particle for the SPION containing particle.

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Figure 4

Protective effect of DEX-Ac nanoparticles on 4-HNE ototoxicity studied on cochlear culture from P3 CD-1 mouse pups. Apical turns are the top two figures. Below this, the middle turns are shown in the left column, while basal turns are presented in the right column. The OHC region is indicated by a bracket (]) and the IHC region is indicated by the arrow symbol (→).

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Figure 5

Quantitative analysis of DEX-Ac particles on 4-HNE ototoxicity studied in the organ of Corti cultures from cochleae of P3 CD-1 mouse pups. Intact hair cell numbers were counted along 100 linear μm of tissue along the basilar membrane. As controls, the organ of Corti cultures without 4-HNE or nanoparticle treatment without DEX-Ac were included. The statistically significant differences in intact hair cell number per 100 μm between DEX-Ac particles+4-HNE group and the 4-HNE group were analyzed by ANOVA with the Tukey post-hoc test. The asterisks ( ∗,  ∗∗, and  ∗∗∗) represent p<0.05, 0.01, and 0.001, respectively.




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