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.
1.
Hiraumi
, H.
, Nakagawa
, T.
, and Ito
, J.
, 2009, “Efficiency of a Transtympanic Approach to the Round Window Membrane Using a Microendoscope
,” Eur. Arch. Otorhinolaryngol.
0937-4477, 266
(3
), pp. 367
–371
.2.
Witte
, M. C.
, and Kasperbauer
, J. L.
, 2000, “Round Window Membrane Permeability to Transforming Growth Factor-Alpha: An In Vitro Study
,” Otolaryngol.-Head Neck Surg.
0194-5998, 123
(1
), pp. 91
–96
.3.
Sun
, J. J.
, Liu
, Y.
, Kong
, W. J.
, Jiang
, P.
, and Jiang
, W.
, 2007, “In Vitro Permeability of Round Window Membrane to Transforming Dexamethasone With Delivery Vehicles—A Dosage Estimation
,” Chin. Med. J. (Engl)
0366-6999, 120
(24
), pp. 2284
–2289
.4.
Li
, G. M.
, Frenz
, D. A.
, Brahmblatt
, S.
, Feghali
, J. G.
, Ruben
, R. J.
, Berggren
, D.
, Arezzo
, J.
, and Van De Water
, T. R.
, 2001, “Round Window Membrane Delivery of L-Methionine Provides Protection From Cisplatin Ototoxicity Without Compromising Chemotherapeutic Efficacy
,” Neurotoxicology
0161-813X, 22
(2
), pp. 163
–176
.5.
Plontke
, S. K.
, Zimmermann
, R.
, Zenner
, H. P.
, and Lowenheim
, H.
, 2006, “Technical Note on Microcatheter Implantation for Local Inner Ear Drug Delivery: Surgical Technique and Safety Aspects
,” Otol. Neurotol.
1531-7129, 27
(7
), pp. 912
–917
.6.
Kopke
, R. D.
, Wassel
, R. A.
, Mondalek
, F.
, Grady
, B.
, Chen
, K. J.
, Liu
, J. Z.
, Gibson
, D.
, and Dormer
, K. J.
, 2006, “Magnetic Nanoparticles: Inner Ear Targeted Molecule Delivery and Middle Ear Implant
,” Audiol. Neuro-Otol.
1420-3030, 11
(2
), pp. 123
–133
.7.
Paulson
, D. P.
, Abuzeid
, W.
, Jiang
, H.
, Oe
, T.
, O’Malley
, B. W.
, and Li
, D. Q.
, 2008, “A Novel Controlled Local Drug Delivery System for Inner Ear Disease
,” Laryngoscope
0023-852X, 118
(4
), pp. 706
–711
.8.
Blum
, J. S.
, and Saltzman
, W. M.
, 2008, “High Loading Efficiency and Tunable Release of Plasmid DNA Encapsulated in Submicron Particles Fabricated From PLGA Conjugated With Poly-L-Lysine
,” J. Controlled Release
0168-3659, 129
(1
), pp. 66
–72
.9.
de la Fuente
, M.
, Csaba
, N.
, Garcia-Fuentes
, M.
, and Alonso
, M. J.
, 2008, “Nanoparticles as Protein and Gene Carriers to Mucosal Surfaces
,” Nanomedicine
1743-5889, 3
(6
), pp. 845
–857
.10.
Kafka
, E. L.
, Braden
, A.
, and Vishwanatha
, J. K.
, 2008, “Characterization of Nanoparticle-Mediated Drug Delivery to NB4: Feasibility of Nanoparticle Use for Cells in Suspension and Blood Diseases
,” Journal of Biomedical Nanotechnology
1550-7033, 4
(2
), pp. 196
–202
.11.
Khang
, G.
, Rhee
, J. M.
, Jeong
, J. K.
, Lee
, J. S.
, Kim
, M. S.
, Cho
, S. H.
, and Lee
, H. B.
, 2003, “Local Drug Delivery System Using Biodegradable Polymers
,” Macromolecular Research
1598-5032, 11
(4
), pp. 207
–223
.12.
Dormer
, K. J.
, Wassel
, R.
, Kopke
, R.
, Chen
, K.
, Grady
, B.
, and Vasquez
, A.
, 2007, “Superparamagnetic-PLGA Non-Viral Vectors for Inner Ear Therapy
,” FASEB J.
0892-6638, 21
(6
), p. A825
.13.
Dormer
, K. J.
, Awasthi
, V.
, Galbraith
, W.
, Kopke
, R. D.
, Chen
, K.
, and Wassel
, R.
, 2008, “Magnetically-Targeted, Technetium 99m-Labeled Nanoparticles to the Inner Ear
,” Journal of Biomedical Nanotechnology
1550-7033, 4
(2
), pp. 174
–184
.14.
Kopke
, R. D.
, Hoffer
, M. E.
, Wester
, D.
, O’Leary
, M. J.
, and Jackson
, R. L.
, 2001, “Targeted Topical Steroid Therapy in Sudden Sensorineural Hearing Loss
,” Otol. Neurotol.
1531-7129, 22
(4
), pp. 475
–479
.15.
Vivero
, R. J.
, Joseph
, D. E.
, Angeli
, S.
, He
, J.
, Chen
, S. B.
, Eshraghi
, A. A.
, Balkany
, T. J.
, and Van De Water
, T. R.
, 2008, “Dexamethasone Base Conserves Hearing From Electrode Trauma-Induced Hearing Loss
,” Laryngoscope
0023-852X, 118
(11
), pp. 2028
–2035
.16.
Dinh
, C.
, Hoang
, K.
, Haake
, S.
, Chen
, S. B.
, Angeli
, S.
, Nong
, E.
, Eshraghi
, A. A.
, Balkany
, T. J.
, and Van De Water
, T. R.
, 2008, “Biopolymer-Released Dexamethasone Prevents Tumor Necrosis Factor Alpha-Induced Loss of Auditory Hair Cells In Vitro: Implications Toward the Development of a Drug-Eluting Cochlear Implant Electrode Array
,” Otol. Neurotol.
1531-7129, 29
(7
), pp. 1012
–1019
.17.
Dinh
, C. T.
, Haake
, S.
, Chen
, S.
, Hoang
, K.
, Nong
, E.
, Eshraghi
, A. A.
, Balkany
, T. J.
, and De Water
, T. R. V.
, 2008, “Dexamethasone Protects Organ of Corti Explants Against Tumor Necrosis Factor-Alpha-Induced Loss of Auditory Hair Cells and Alters the Expression Levels of Apoptosis-Related Genes
,” Neuroscience
0306-4522, 157
(2
), pp. 405
–413
.18.
Borkholder
, D. A.
, 2008, “State-of-the-Art Mechanisms of Intracochlear Drug Delivery
,” Curr. Opin. Otolaryngol. Head Neck Surg.
1068-9508, 16
(5
), pp. 472
–477
.19.
Gao
, X.
, Chen
, K.
, and Kopke
, R.
, 2008, “Protective Effects of GSHe on Cochlear Hair Cells From 4-HNE and Neomycin Ototoxicity
,” Baltimore, MD.20.
Bilati
, U.
, Allemann
, E.
, and Doelker
, E.
, 2003, “Sonication Parameters for the Preparation of Biodegradable Nanocapsules of Controlled Size by the Double Emulsion Method
,” Pharm. Dev. Technol.
1083-7450, 8
(1
), pp. 1
–9
.21.
Wassel
, R. A.
, Grady
, B.
, Kopke
, R. D.
, and Dormer
, K. J.
, 2007, “Dispersion of Super Paramagnetic Iron Oxide Nanoparticles in Poly(D,L-Lactide-Co-Glycolide) Microparticles
,” Colloids Surf., A
0927-7757, 292
(2–3
), pp. 125
–130
.22.
Song
, X. R.
, Zhao
, Y.
, Wu
, W. B.
, Bi
, Y. Q.
, Cai
, Z.
, Chen
, Q. H.
, Li
, Y. B.
, and Hou
, S. X.
, 2008, “PLGA Nanoparticles Simultaneously Loaded With Vincristine Sulfate and Verapamil Hydrochloride: Systematic Study of Particle Size and Drug Entrapment Efficiency
,” Int. J. Pharm.
0378-5173, 350
(1–2
), pp. 320
–329
.23.
Tewes
, F.
, Munnier
, E.
, Antoon
, B.
, Okassa
, L. N.
, Cohen-Jonathan
, S.
, Marchais
, H.
, Douziech-Eyrolles
, L.
, Souce
, M.
, Dubois
, P.
, and Chourpa
, I.
, 2007, “Comparative Study of Doxorubicin-Loaded Poly(Lactide-Co-Glycolide) Nanoparticles Prepared by Single and Double Emulsion Methods
,” Eur. J. Pharm. Biopharm.
0939-6411, 66
(3
), pp. 488
–492
.24.
Zigoneanu
, I. G.
, Astete
, C. E.
, and Sabliov
, C. M.
, 2008, “Nanoparticles With Entrapped Alpha-Tocopherol: Synthesis, Characterization, and Controlled Release
,” Nanotechnology
0957-4484, 19
(10
), p. 105606
.25.
Gomez-Gaete
, C.
, Fattal
, E.
, Silva
, L.
, Besnard
, M.
, and Tsapis
, N.
, 2008, “Dexamethasone Acetate Encapsulation Into Trojan Particles
,” J. Controlled Release
0168-3659, 128
(1
), pp. 41
–49
.26.
Niwa
, T.
, Takeuchi
, H.
, Hino
, T.
, Kunou
, N.
, and Kawashima
, Y.
, 1993, “Preparations of Biodegradable Nanospheres of Water-Soluble and Insoluble Drugs With D,L-Lactide Glycolide Copolymer by a Novel Spontaneous Emulsification Solvent Diffusion Method, and the Drug Release Behavior
,” J. Controlled Release
0168-3659, 25
(1–2
), pp. 89
–98
.27.
Thote
, A. J.
, Chappell
, J. T.
, Gupta
, R. B.
, and Kumar
, R.
, 2005, “Reduction in the Initial-Burst Release by Surface Crosslinking of PLGA Microparticles Containing Hydrophilic or Hydrophobic Drugs
,” Drug Dev. Ind. Pharm.
0363-9045, 31
(1
), pp. 43
–57
.28.
Jaraswekin
, S.
, Prakongpan
, S.
, and Bodmeier
, R.
, 2007, “Effect of Poly(Lactide-Co-Glycolide) Molecular Weight on the Release of Dexamethasone Sodium Phosphate From Microparticles
,” J. Microencapsul.
0265-2048, 24
(2
), pp. 117
–128
.29.
Eroglu
, H.
, Kas
, H. S.
, Oner
, L.
, Turkoglu
, O. F.
, Akalan
, N.
, Sargon
, M. F.
, and Ozer
, N.
, 2001, “The In-Vitro and In-Vivo Characterization of PLGA: L-PLA Microspheres Containing Dexamethasone Sodium Phosphate
,” J. Microencapsul.
0265-2048, 18
(5
), pp. 603
–612
.30.
Langer
, R.
, 1990, “New Methods of Drug Delivery
,” Science
0036-8075, 249
(4976
), pp. 1527
–1533
.31.
Einmahl
, S.
, Zignani
, M.
, Varesio
, E.
, Heller
, J.
, Veuthey
, J. L.
, Tabatabay
, C.
, and Gurny
, R.
, 1999, “Concomitant and Controlled Release of Dexamethasone and 5-Fluorouracil From Poly(Ortho Ester)
,” Int. J. Pharm.
0378-5173, 185
(2
), pp. 189
–198
.32.
Gomez-Graete
, C.
, Tsapis
, N.
, Besnard
, M.
, Bochot
, A.
, and Fattal
, E.
, 2007, “Encapsulation of Dexamethasone Into Biodegradable Polymeric Nanoparticles
,” Int. J. Pharm.
0378-5173, 331
(2
), pp. 153
–159
.33.
Xu
, J. F.
, Wang
, Y. S.
, Li
, Y.
, Yang
, X. M.
, Zhang
, P.
, Hou
, H. Y.
, Shi
, Y. Y.
, and Song
, C. X.
, 2007, “Inhibitory Efficacy of Intravitreal Dexamethasone Acetate-Loaded PLGA Nanoparticles on Choroidal Neovascularization in a Laser-Induced Rat Model
,” J. Ocul. Pharmacol. Ther.
1080-7683, 23
(6
), pp. 527
–540
.34.
Sha
, S. -H.
, Taylor
, R.
, Forge
, A.
, and Schacht
, J.
, 2001, “Differential Vulnerability of Basal and Apical Hair Cells Is Based on Intrinsic Susceptibility to Free Radicals
,” Hear. Res.
0378-5955, 155
(1–2
), pp. 1
–8
.Copyright © 2011
by American Society of Mechanical Engineers
You do not currently have access to this content.
