Recent Advances on Acoustic, Ultrasonic, and Magnetic Drug Delivery

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: closed (25 January 2024) | Viewed by 13096

Special Issue Editors


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Guest Editor
Adelaide Medical School, The University of Adelaide, North Terrace, Adelaide, SA 5005, Australia
Interests: acoustic drug delivery; magnetic drug delivery; Computational Fluid Dynamics (CFD); biomechanics; rhinology

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Guest Editor
Institute of Computational Biology, Helmholtz Zentrum München, 85764 Munich, Germany
Interests: biofluid dynamics; pulmonary aerosol delivery modeling; computational fluid dynamics; machine learning
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Special Issue Information

Dear Colleagues,

Using an active targeting drug delivery approach, the efficiency of drug delivery can be significantly increased when compared with the passive approach. Acoustic and magnetic drug delivery techniques are two novel active drug delivery approaches. The use of acoustics in biomedical practices has been expanded from diagnostic applications to non-invasive drug delivery. The use of acoustics in drug delivery procedures can be divided into two categories: ultrasonic-enhanced drug delivery (known as high-intensity focused ultrasound (HIFU)) and low-frequency acoustic drug delivery (ADD). In the former, the acoustic frequency (f) that is used for drug delivery falls in the spectrum of f > 20 kHz, which is beyond the threshold of human hearing. In the latter drug delivery method (i.e., ADD), the low frequencies refer to frequencies below 20 kHz, which can be sensed by the human ear. The use of transcutaneous ultrasound for therapeutic purposes has been shown to be a promising active targeting approach when used for internal treatment or in the blood circulation system. On the other hand, a low-frequency acoustic field has recently been demonstrated to be advantageous in nasal drug delivery, especially for drug delivery to the paranasal sinuses. Studies have demonstrated that low-frequency drug delivery to the paranasal sinuses can enhance drug deposition in the sinuses significantly.

Since 1970s, when microparticles coated with polymer were first developed, magnetic drug targeting (MDT) using drug-loaded microparticles attracted great attention from many researchers seeking to elaborate on drug delivery options to targeted sites. In MDT, an external magnetic field manipulates the magnetic drug carriers to deliver a drug to targeted locations in the body and retains them there, which can reduce the adverse side effect and improve the drug delivery efficiency significantly. MDT can also be used to kill the tumour and cancer cells in a different way: magnetic microparticles are injected into the body and then an electromagnetic field is applied externally to increase the temperature of the particles, using hysteresis loss, to destroy the tumour/cancer.

The journal Pharmaceuticals invites both reviews and original articles that shed light on the challenges and opportunities of using the magnetic field, acoustic wave, and pulsating flow in drug delivery enhancement as well as in the diagnosis of various diseases. Topics include but are not limited to: Targeted Drug delivery, Acoustic Drug Delivery, Magnetic drug targeting, Pulsating Flow, high-intensity focused ultrasound (HIFU), Acoustic Rhinometry, Chemotherapy, Hyperthermia, Chemopotentiation, Ultrasonography, Cavitation, Lung Drug Delivery, Nasal Drug Delivery, Computational Fluid Dynamics, Finite Element Analysis, Biomechanics of Human Airways, Chronic Rhinosinusitis. The collection of manuscripts will be published as a Special Issue of the journal.

Dr. Oveis Pourmehran
Dr. Ali Farnoud
Guest Editors

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Keywords

  • ultrasound
  • acoustic drug delivery
  • magnetic drug delivery
  • acoustic rhinometry
  • computational fluid dynamics (CFD)

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Published Papers (4 papers)

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Research

20 pages, 6474 KiB  
Article
Numerical and Experimental Analysis of Drug Inhalation in Realistic Human Upper Airway Model
by Morsal Momeni Larimi, Arash Babamiri, Mohit Biglarian, Abas Ramiar, Reza Tabe, Kiao Inthavong and Ali Farnoud
Pharmaceuticals 2023, 16(3), 406; https://doi.org/10.3390/ph16030406 - 7 Mar 2023
Cited by 5 | Viewed by 2070
Abstract
The demand for a more efficient and targeted method for intranasal drug delivery has led to sophisticated device design, delivery methods, and aerosol properties. Due to the complex nasal geometry and measurement limitations, numerical modeling is an appropriate approach to simulate the airflow, [...] Read more.
The demand for a more efficient and targeted method for intranasal drug delivery has led to sophisticated device design, delivery methods, and aerosol properties. Due to the complex nasal geometry and measurement limitations, numerical modeling is an appropriate approach to simulate the airflow, aerosol dispersion, and deposition for the initial assessment of novel methodologies for better drug delivery. In this study, a CT-based, 3D-printed model of a realistic nasal airway was reconstructed, and airflow pressure, velocity, turbulent kinetic energy (TKE), and aerosol deposition patterns were simultaneously investigated. Different inhalation flowrates (5, 10, 15, 30, and 45 L/min) and aerosol sizes (1, 1.5, 2.5, 3, 6, 15, and 30 µm) were simulated using laminar and SST viscous models, with the results compared and verified by experimental data. The results revealed that from the vestibule to the nasopharynx, the pressure drop was negligible for flow rates of 5, 10, and 15 L/min, while for flow rates of 30 and 40 L/min, a considerable pressure drop was observed by approximately 14 and 10%, respectively. However, from the nasopharynx and trachea, this reduction was approximately 70%. The aerosol deposition fraction alongside the nasal cavities and upper airway showed a significant difference in pattern, dependent on particle size. More than 90% of the initiated particles were deposited in the anterior region, while just under 20% of the injected ultrafine particles were deposited in this area. The turbulent and laminar models showed slightly different values for the deposition fraction and efficiency of drug delivery for ultrafine particles (about 5%); however, the deposition pattern for ultrafine particles was very different. Full article
(This article belongs to the Special Issue Recent Advances on Acoustic, Ultrasonic, and Magnetic Drug Delivery)
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15 pages, 4613 KiB  
Article
Acoustic Aerosol Delivery: Assessing of Various Nasal Delivery Techniques and Medical Devices on Intrasinus Drug Deposition
by Lara Leclerc, Nathalie Prévôt, Sophie Hodin, Xavier Delavenne, Heribert Mentzel, Uwe Schuschnig and Jérémie Pourchez
Pharmaceuticals 2023, 16(2), 135; https://doi.org/10.3390/ph16020135 - 17 Jan 2023
Cited by 4 | Viewed by 1634
Abstract
This study aims to evaluate the impact of the nasal delivery technique and nebulizing technologies (using different frequencies of oscillating airflow) for acoustic aerosol targeting of maxillary sinuses. Sodium fluoride (chemical used as a marker), tobramycin (drug used as a marker) and 99m [...] Read more.
This study aims to evaluate the impact of the nasal delivery technique and nebulizing technologies (using different frequencies of oscillating airflow) for acoustic aerosol targeting of maxillary sinuses. Sodium fluoride (chemical used as a marker), tobramycin (drug used as a marker) and 99mTc-DTPA (radiolabel aerosol) were used to assess the intrasinus aerosol deposition on a nasal cast. Two commercial medical devices (PARI SINUS nebulizer and NL11SN ATOMISOR nebulizer) and various nasal delivery techniques (one or two nostrils connected to the aerosol inlet, the patient with the soft palate closed or open during the acoustic administration of the drug, the presence or not of flow resistance in the nostril opposite to the one allowing the aerosol to be administered) were evaluated. The closed soft palate condition showed a significant increase in drug deposition even though no significant difference in the rest of the nasal fossae was noticed. Our results clearly demonstrated a higher intrasinus aerosol deposition (by a factor 2–3; respectively 0.03 ± 0.007% vs. 0.003 ± 0.0002% in the right maxillary sinus and 0.027 ± 0.006% vs. 0.013 ± 0.004% in the left maxillary sinus) using the acoustic airflow generated by the PARI SINUS compared to the NL11SN ATOMISOR. The results clearly demonstrated that the optimal conditions for aerosol deposition in the maxillary sinuses were obtained with a closed soft palate. Thus, the choice of the nebulizing technology (and mainly the frequency of the pulsating aerosol generated) and also the recommendation of the best nasal delivery technique are key factors to improve intrasinus aerosol deposition. Full article
(This article belongs to the Special Issue Recent Advances on Acoustic, Ultrasonic, and Magnetic Drug Delivery)
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14 pages, 3550 KiB  
Article
Numerical and Machine Learning Analysis of the Parameters Affecting the Regionally Delivered Nasal Dose of Nano- and Micro-Sized Aerosolized Drugs
by Ali Farnoud, Hesam Tofighian, Ingo Baumann, Kaveh Ahookhosh, Oveis Pourmehran, Xinguang Cui, Vincent Heuveline, Chen Song, Sarah Vreugde, Peter-John Wormald, Michael P. Menden and Otmar Schmid
Pharmaceuticals 2023, 16(1), 81; https://doi.org/10.3390/ph16010081 - 6 Jan 2023
Cited by 6 | Viewed by 4315
Abstract
The nasal epithelium is an important target for drug delivery to the nose and secondary organs such as the brain via the olfactory bulb. For both topical and brain delivery, the targeting of specific nasal regions such as the olfactory epithelium (brain) is [...] Read more.
The nasal epithelium is an important target for drug delivery to the nose and secondary organs such as the brain via the olfactory bulb. For both topical and brain delivery, the targeting of specific nasal regions such as the olfactory epithelium (brain) is essential, yet challenging. In this study, a numerical model was developed to predict the regional dose as mass per surface area (for an inhaled mass of 2.5 mg), which is the biologically most relevant dose metric for drug delivery in the respiratory system. The role of aerosol diameter (particle diameter: 1 nm to 30 µm) and inhalation flow rate (4, 15 and 30 L/min) in optimal drug delivery to the vestibule, nasal valve, olfactory and nasopharynx is assessed. To obtain the highest doses in the olfactory region, we suggest aerosols with a diameter of 20 µm and a medium inlet air flow rate of 15 L/min. High deposition on the olfactory epithelium was also observed for nanoparticles below 1 nm, as was high residence time (slow flow rate of 4 L/min), but the very low mass of 1 nm nanoparticles is prohibitive for most therapeutic applications. Moreover, high flow rates (30 L/min) and larger micro-aerosols lead to highest doses in the vestibule and nasal valve regions. On the other hand, the highest drug doses in the nasopharynx are observed for nano-aerosol (1 nm) and fine microparticles (1–20 µm) with a relatively weak dependence on flow rate. Furthermore, using the 45 different inhalation scenarios generated by numerical models, different machine learning models with five-fold cross-validation are trained to predict the delivered dose and avoid partial differential equation solvers for future predictions. Random forest and gradient boosting models resulted in R2 scores of 0.89 and 0.96, respectively. The aerosol diameter and region of interest are the most important features affecting delivered dose, with an approximate importance of 42% and 47%, respectively. Full article
(This article belongs to the Special Issue Recent Advances on Acoustic, Ultrasonic, and Magnetic Drug Delivery)
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21 pages, 6095 KiB  
Article
Magnetic Nanoparticles for Drug Delivery through Tapered Stenosed Artery with Blood Based Non-Newtonian Fluid
by Muhammad Mubashir Bhatti, Sadiq M. Sait and Rahmat Ellahi
Pharmaceuticals 2022, 15(11), 1352; https://doi.org/10.3390/ph15111352 - 1 Nov 2022
Cited by 56 | Viewed by 3848
Abstract
Nanoparticles play an essential role in biomedical applications. A most promising area in nanomedicine is drug targeting which is done with the aid of magnetized nanoparticles. In this study, the hemodynamics of hybrid nanofluid flow with gold and copper nanoparticles suspended in it [...] Read more.
Nanoparticles play an essential role in biomedical applications. A most promising area in nanomedicine is drug targeting which is done with the aid of magnetized nanoparticles. In this study, the hemodynamics of hybrid nanofluid flow with gold and copper nanoparticles suspended in it is investigated. This research primarily focuses on magnetic drug delivery which is propagated through a tapered stenosed artery under three situations, including converging, diverging, and non-tapering arteries. To explore the rheological characteristics of blood, a Sutterby fluid, which is a non-Newtonian fluid, is postulated. The energy equation also incorporates the effects of the magnetic field and joule heating, as well as the viscous dissipation function. Lubrication theory provides a mathematical framework for model formulation. The hypothesized modeling is simplified to a set of nonlinear differential equations that are then solved using a perturbation method up to the second order of approximation. Graphs are used to describe the outcomes of different evolving parameters. The Sutterby fluid parameter opposes the flow negligibly, whereas the Hartmann number and thermal Grashof number strengthen the flow field. Copper nanoparticles (in the absence of gold nanoparticles) are observed to deplete the thermal profile substantially more than gold nanoparticles. Nevertheless, the thermal profile is enhanced by the presence of both nanoparticles (hybrid nanofluids). For greater values of the Sutterby fluid parameter, the wall shear stress has been observed to rise considerably, whereas the inverse is true for the Hartmann number and the thermal Grashof number. The present results have been improved to give significant information for biomedical scientists who are striving to study blood flow in stenosis situations, as well as for those who will find the knowledge valuable in the treatment of different diseases. Full article
(This article belongs to the Special Issue Recent Advances on Acoustic, Ultrasonic, and Magnetic Drug Delivery)
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