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

Author(s):  
Xinsheng Gao ◽  
Youdan Wang ◽  
Kejian Chen ◽  
Brian P. Grady ◽  
Kenneth J. Dormer ◽  
...  

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 ∼15 nm 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.

Nanomaterials ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 1623 ◽  
Author(s):  
Gabriela Fabiola Știufiuc ◽  
Ștefan Nițică ◽  
Valentin Toma ◽  
Cristian Iacoviță ◽  
Dietrich Zahn ◽  
...  

By carefully controlling the electrostatic interactions between cationic liposomes, which already incorporate magnetic nanoparticles in the bilayers, and anionic gold nanoparticles, a new class of versatile multifunctional nanohybrids (plasmonic magneto-liposomes) that could have a major impact in drug delivery and controlled release applications has been synthesized. The experimental results confirmed the successful synthesis of hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) and polyethylene glycol functionalized (PEGylated) gold nanoparticles (AuNPs). The SPIONs were incorporated in the liposomal lipidic bilayers, thus promoting the formation of cationic magnetoliposomes. Different concentrations of SPIONs were loaded in the membrane. The cationic magnetoliposomes were decorated with anionic PEGylated gold nanoparticles using electrostatic interactions. The successful incorporation of SPIONs together with the modifications they generate in the bilayer were analyzed using Raman spectroscopy. The plasmonic properties of the multifunctional nanohybrids were investigated using UV-Vis absorption and (surface-enhanced) Raman spectroscopy. Their hyperthermic properties were recorded at different frequencies and magnetic field intensities. After the synthesis, the nanosystems were extensively characterized in order to properly evaluate their potential use in drug delivery applications and controlled release as a result of the interaction with an external stimulus, such as an NIR laser or alternating magnetic field.


Background: Superparamagnetic iron oxide nanoparticles (SPION) are widely used in various biomedical technologies, in particular, as carriers for drug delivery to the target. Since SPION-drug complexes are planned to be used in vivo, it is necessary to find out if competitive binding of nanoparticles with biologically important macromolecules (nucleic acids and proteins) is possible. Objectives: To investigate the possibility of complexation of iron oxide nanoparticles with DNA and serum albumin. Materials and methods: Bare and sodium citrate coated SPION with different surface charges, bovine serum albumin (BSA) and calf thymus DNA were used. The complexes of SPION and macromolecules were precipitated by an external magnetic field. The research was carried out by spectrophotometry in visible and ultraviolet ranges. Results: To study SPION interactions with DNA and BSA, the spectra of supernatants of the binary systems were compared with the spectra of the corresponding control macromolecules solutions. In the DNA-SPION systems, a decrease in the DNA absorption is observed only for bare nanoparticles. Our estimation shows that the maximum possible concentration ratio of bound DNA to SPION is about 2.5×10-4 mol/g. The addition of sodium citrate coated SPION to the DNA solution does not cause any spectral changes of the supernatant. The interaction of BSA with SPION, coated with sodium citrate, leads to a slight increase in supernatant absorption compared with the one of the control protein solution. It can be caused by the fact that the resulting complexes are not precipitated by a magnetic field. No difference between the spectrum of the supernatant of BSA-bare SPION system and the control protein solution was observed. Conclusions: The obtained spectrophotometric results demonstrate the formation of complexes between DNA and bare iron oxide nanoparticles as well as between BSA and the nanoparticles, coated with sodium citrate. The maximum concentration ratio of bound DNA and bare SPION was obtained for the investigated system. It is necessary to take into account when SPION are used as carriers for drug delivery.


Nanomedicine ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. 1339-1354 ◽  
Author(s):  
Daniela Buckiová ◽  
Sanjeev Ranjan ◽  
Tracey A Newman ◽  
Alexander H Johnston ◽  
Rohit Sood ◽  
...  

2007 ◽  
Vol 137 (4) ◽  
pp. 619-623 ◽  
Author(s):  
Xianxi Ge ◽  
Ronald L. Jackson ◽  
Jianzhong Liu ◽  
Elizabeth A. Harper ◽  
Michael E. Hoffer ◽  
...  

Objectives To study the distribution of polylactic/glycolic acid–encapsulated iron oxide nanoparticles (PLGA-NPs) in chinchilla cochleae after application on the round window membrane (RWM). Study Design and Setting Six chinchillas (12 ears) were equally divided into controls (no treatments) and experimen-tals (PLGA-NP with or without magnetic exposure). After 40 minutes of PLGA-NP placement on the RWM, perilymph was withdrawn from the scala tympani. The RWM and cochleae were fixed with 2.5% glutaraldehyde and processed for transmission electron microscopy. Results Nanoparticles were found in cochleae with or without exposure to magnet forces appearing in the RWM, perilymph, endolymph, and multiple locations in the organ of Corti. Electron energy loss spectroscopy confirmed iron elements in nanoparticles. Conclusion The nanoparticles were distributed throughout the inner ear after application on the chinchilla RWM, with and without magnetic forces. Significance PLGA-NP applied to the RWM may have potential for sustained therapy to the inner ear.


Author(s):  
Youdan Wang ◽  
Xinsheng Gao ◽  
Satish Kuriyavar ◽  
David Bourne ◽  
Brian Grady ◽  
...  

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.


2014 ◽  
Vol 174 ◽  
pp. 171-176 ◽  
Author(s):  
David A. Borkholder ◽  
Xiaoxia Zhu ◽  
Robert D. Frisina

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1590
Author(s):  
Madhuri Dandamudi ◽  
Peter McLoughlin ◽  
Gautam Behl ◽  
Sweta Rani ◽  
Lee Coffey ◽  
...  

The current treatment for the acquired retinal vasculopathies involves lifelong repeated intravitreal injections of either anti-vascular endothelial growth factor (VEGF) therapy or modulation of inflammation with steroids. Consequently, any treatment modification that decreases this treatment burden for patients and doctors alike would be a welcome intervention. To that end, this research aims to develop a topically applied nanoparticulate system encapsulating a corticosteroid for extended drug release. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) supports the controlled release of the encapsulated drug, while surface modification of these NPs with chitosan might prolong the mucoadhesion ability leading to improved bioavailability of the drug. Triamcinolone acetonide (TA)-loaded chitosan-coated PLGA NPs were fabricated using the oil-in-water emulsion technique. The optimized surface-modified NPs obtained using Box-Behnken response surface statistical design were reproducible with a particle diameter of 334 ± 67.95 to 386 ± 15.14 nm and PDI between 0.09 and 0.15. These NPs encapsulated 55–57% of TA and displayed a controlled release of the drug reaching a plateau in 27 h. Fourier-transform infrared spectroscopic (FTIR) analysis demonstrated characteristic peaks for chitosan (C-H, CONH2 and C-O at 2935, 1631 and 1087 cm−1, respectively) in chitosan-coated PLGA NPs. This result data, coupled with positive zeta potential values (ranged between +26 and +33 mV), suggests the successful coating of chitosan onto PLGA NPs. Upon coating of the NPs, the thermal stability of the drug, polymer, surfactant and PLGA NPs have been enhanced. The characteristics of the surface-modified NPs supports their use as potential candidates for topical ocular drug delivery for acquired retinal vasculopathies.


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