Minimally invasive drug delivery to the cochlea through application of nanoparticles to the round window membrane

Nanomedicine ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. 1339-1354 ◽  
Author(s):  
Daniela Buckiová ◽  
Sanjeev Ranjan ◽  
Tracey A Newman ◽  
Alexander H Johnston ◽  
Rohit Sood ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Minimally Invasive ◽  
Round Window ◽  
Round Window Membrane

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

2010 ◽  
Vol 1 (3) ◽  
Author(s):  
Xinsheng Gao ◽  
Youdan Wang ◽  
Kejian Chen ◽  
Brian P. Grady ◽  
Kenneth J. Dormer ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Drug Delivery ◽  
Permanent Magnets ◽  
Round Window ◽  
Superparamagnetic Iron Oxide ◽  
Clinical Problem ◽  
Plga Nanoparticles ◽  
Round Window Membrane ◽  
Water Emulsion ◽  
Coumarin 6

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.

scholarly journals Round window membrane intracochlear drug delivery enhanced by induced advection

2014 ◽  
Vol 174 ◽  
pp. 171-176 ◽  
Author(s):  
David A. Borkholder ◽  
Xiaoxia Zhu ◽  
Robert D. Frisina
Keyword(s):  
Drug Delivery ◽  
Round Window ◽  
Round Window Membrane

scholarly journals A modular microreservoir for active implantable drug delivery

2019 ◽  
Author(s):  
Farzad Forouzandeh ◽  
Xiaoxia Zhu ◽  
Nuzhet N. Ahamed ◽  
Joseph P. Walton ◽  
Robert D. Frisina ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Sacrificial Layer ◽  
Round Window ◽  
Round Window Membrane ◽  
Basal Region ◽  
Distortion Product Otoacoustic Emission ◽  
Subcutaneous Implantation ◽  
Restoring Force ◽  
Distortion Product

ABSTRACTActive implantable microscale reservoir-based drug delivery systems enabled novel and effective drug delivery concepts for both systemic and localized drug delivery applications. These systems typically consist of a drug reservoir and an active pumping mechanism for precise delivery of drugs. Here we present a stand-alone, refillable, scalable, and fully implantable microreservoir platform to be integrated with micropumps as a storing component of active implantable drug delivery microsystems. The microreservoir was fabricated with 3D-printing technology, enabling miniature, scalable, and planar structure, optimized for subcutaneous implantation especially in small animals (e.g., mouse), while being readily scalable for larger animals and human translation. Three different capacities of the microreservoir (1 μL, 10 μL, and 100 μL) were fabricated and characterized all with 3 mm thickness. The microreservoir consists of two main parts: a cavity for long-term drug storage with an outlet microtubing (250 μm OD, 125 μm ID), and a refill port for transcutaneous refills through a septum. The cavity membrane is fabricated with thin Parylene-C layers using a polyethylene glycol sacrificial layer, minimizing restoring force and hence backflow, as fluid is discharged. This feature enables integration to normally-open mechanisms and improves pumping efficiency when integrated to normally-closed pumps. The results of in vitro optimization and characterization of the cavity membrane show 95% extraction percentage of the cavity with insignificant (2%) backflow due to restoring force of the membrane. The refill port septum thickness is minimized down to 1 mm by a novel pre-compression concept, while capable of ~65000 injections with 30 Ga non-coring needles without leakage under 100 kPa (4× greater than physiological backpressure). To demonstrate integrability of the microreservoir to an active micropump, the 10 μL microreservoir was integrated to a micropump recently developed in our laboratory, making an implantable drug delivery microsystem. Two different microsystems were subcutaneously implanted in two mice, and the outlet microtubing was implanted into the round window membrane niche for infusion of a known ototoxic compound (sodium salicylate) at 50 nL/min for 20 min. Real-time shifts in distortion product otoacoustic emission thresholds and amplitudes were measured during the infusion. The in vivo results show a mean shift of 22.1 dB after 20 min for the most basal region, matching with syringe pump results. A biocompatibility experiment was performed on the microsystem for six months to assess design and fabrication suitability for chronic subcutaneous implantation and clinical translational development. The results demonstrate very favorable signs of biocompatibility for long-term implantation. Although tested here on mice for a specific inner ear application, this low-cost design and fabrication methodology is scalable for use in larger animals and human for different applications/delivery sites.

scholarly journals A Wirelessly Controlled Scalable 3D-Printed Microsystem for Drug Delivery

2021 ◽  
Vol 14 (6) ◽  
pp. 538
Author(s):  
Farzad Forouzandeh ◽  
Nuzhet N. Ahamed ◽  
Xiaoxia Zhu ◽  
Parveen Bazard ◽  
Krittika Goyal ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Printed Circuit Board ◽  
Low Cost ◽  
Round Window ◽  
Circuit Board ◽  
Round Window Membrane ◽  
Distortion Product Otoacoustic Emission ◽  
Distortion Product ◽  
3D Printed

Here we present a 3D-printed, wirelessly controlled microsystem for drug delivery, comprising a refillable microreservoir and a phase-change peristaltic micropump. The micropump structure was inkjet-printed on the back of a printed circuit board around a catheter microtubing. The enclosure of the microsystem was fabricated using stereolithography 3D printing, with an embedded microreservoir structure and integrated micropump. In one configuration, the microsystem was optimized for murine inner ear drug delivery with an overall size of 19 × 13 × 3 mm3. Benchtop results confirmed the performance of the device for reliable drug delivery. The suitability of the device for long-term subcutaneous implantation was confirmed with favorable results of implantation of a microsystem in a mouse for six months. The drug delivery was evaluated in vivo by implanting four different microsystems in four mice, while the outlet microtubing was implanted into the round window membrane niche for infusion of a known ototoxic compound (sodium salicylate) at 50 nL/min for 20 min. Real-time shifts in distortion product otoacoustic emission thresholds and amplitudes were measured during the infusion, demonstrating similar results with syringe pump infusion. Although demonstrated for one application, this low-cost design and fabrication methodology is scalable for use in larger animals and humans for different clinical applications/delivery sites.

scholarly journals Formation and characterisation of hydrogel diffusion channels for directed drug delivery

2019 ◽  
Vol 5 (1) ◽  
pp. 323-325
Author(s):  
Thomas Eickner ◽  
Stefanie Kohse ◽  
Sabine Illner ◽  
Stefan Oschatz ◽  
Michael Teske ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Layer Thickness ◽  
Drug Transport ◽  
Round Window ◽  
Ambient Air ◽  
Round Window Membrane ◽  
Sustained Drug Release ◽  
Liquid Environment ◽  
Drug Eluting ◽  
The One

AbstractDrug Delivery Systems (DDS) are frequently operating in a surrounding liquid environment, such as blood in the case of drug-eluting stents or perilymph in the case of cochlear implants. However, there is also a demand for systems with sustained drug release in predominantly dry environments, mostly consisting of ambient air. Examples are the treatment of diseases located in the middle ear or the paranasal sinuses. On the one hand, due to the lack of transportation media, the functionality of a polymer/drug combination for delayed release would be limited in such environments. On the other hand, these environments are generally equipped with mucus membranes. Hence, a somewhat humid surrounding is ensured. In this study, a concept of a hydrogel equipped DDS for drug delivery through the round window membrane is presented, addressing two objectives. First objective is to ensure the drug transport by serving as a diffusion channel. For instance the route to the drug target destination, the round window membrane, can be provided by a hydrogel. The second objective is to ensure the adhesion to the membrane. Two promising approaches are presented in this study: The photo induced immobilisation of PEGDA700, as well as the immobilisation of chitosan on poly(l-lactid) (PLLA). For both approaches PLLA specimen had to be modified with oxygen plasma followed by activation for crosslinking with subsequent immobilisation of the hydrogel. With these methods a layer thickness of at least 5 μm was achieved. All steps were characterized with contact angle measurements. After the immobilization of the hydrogel, the swelling factor, as well as the layer thickness was examined.

scholarly journals Determination of the Round Window Niche Anatomy Using Cone Beam Computed Tomography Imaging as Preparatory Work for Individualized Drug-Releasing Implants

2021 ◽  
Vol 7 (5) ◽  
pp. 79
Author(s):  
Farnaz Matin ◽  
Ziwen Gao ◽  
Felix Repp ◽  
Samuel John ◽  
Thomas Lenarz ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Drug Delivery ◽  
Inner Ear ◽  
Cone Beam Computed Tomography ◽  
Round Window ◽  
Local Drug Delivery ◽  
Cone Beam ◽  
Round Window Membrane ◽  
Round Window Niche ◽  
Bony Overhang

Modern therapy of inner ear disorders is increasingly shifting to local drug delivery using a growing number of pharmaceuticals. Access to the inner ear is usually made via the round window membrane (RWM), located in the bony round window niche (RWN). We hypothesize that the individual shape and size of the RWN have to be taken into account for safe reliable and controlled drug delivery. Therefore, we investigated the anatomy and its variations. Cone beam computed tomography (CBCT) images of 50 patients were analyzed. Based on the reconstructed 3D volumes, individual anatomies of the RWN, RWM, and bony overhang were determined by segmentation using 3D SlicerTM with a custom build plug-in. A large individual anatomical variability of the RWN with a mean volume of 4.54 mm3 (min 2.28 mm3, max 6.64 mm3) was measured. The area of the RWM ranged from 1.30 to 4.39 mm2 (mean: 2.93 mm2). The bony overhang had a mean length of 0.56 mm (min 0.04 mm, max 1.24 mm) and the shape was individually very different. Our data suggest that there is a potential for individually designed and additively manufactured RWN implants due to large differences in the volume and shape of the RWN.

Optical Properties of Photodynamic Therapy Drugs in Different Environments: The Paradigmatic Case of Temoporfin

2020 ◽  
Author(s):  
busenur Aslanoglu ◽  
Ilya Yakavets ◽  
Vladimir Zorin ◽  
Henri-Pierre Lassalle ◽  
Francesca Ingrosso ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Optical Properties ◽  
Photodynamic Therapy ◽  
Minimally Invasive ◽  
Visible Light ◽  
Cancer Treatment ◽  
Singlet Oxygen ◽  
Tumor Cells ◽  
Molecular Oxygen ◽  
Computational Tools

Computational tools have been used to study the photophysical and photochemical features of photosensitizers in photodynamic therapy (PDT) –a minimally invasive, less aggressive alternative for cancer treatment. PDT is mainly based by the activation of molecular oxygen through the action of a photoexcited sensitizer (photosensitizer). Temoporfin, widely known as mTHPC, is a second-generation photosensitizer, which produces the cytotoxic singlet oxygen when irradiated with visible light and hence destroys tumor cells. However, the bioavailability of the mostly hydrophobic photosensitizer, and hence its incorporation into the cells, is fundamental to achieve the desired effect on malignant tissues by PDT. In this study, we focus on the optical properties of the temoporfin chromophore in different environments –in <i>vacuo</i>, in solution, encapsulated in drug delivery agents, namely cyclodextrin, and interacting with a lipid bilayer.

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