 | It has been suggested that this article be merged into Sonophoresis . (Discuss) Proposed since December 2023. |
Phonophoresis, also known as sonophoresis, is the method of using ultrasound waves to increase skin permeability in order to improve the effectiveness of transdermal drug delivery. This method intersects drug delivery and ultrasound therapy. By assisting transdermal drug delivery, phonophoresis can be a painless treatment and an alternative to a needle.
The primary purpose of phonophoresis is to assist in transdermal drug delivery, usually with the help of a coupling agent or medium. Transdermal drug delivery sometimes does not permeate the skin to reach a targeted area within the body because of the stratum corneum layer of the skin, a layer that prevents foreign substances from penetrating the body. [1] [2] [3] Transdermal drug delivery is patient-compliance, [4] usually avoids digestive system degradation, [5] and has the ability to use drugs with short half-lives. [6]
Phonophoresis can be performed using two main methods: The first is simultaneous treatment, where the drug can be applied at the same time as the ultrasound. The second method is pretreatment, where the ultrasound is used briefly before drug delivery. [5] [6] [7] [4] This is to ensure that the skin is permeable prior to the drug being applied.
When using an ultrasound, cavities will develop due to the pressure change. Stable cavitation describes the repetitive oscillations of a cavity bubble, while inertial cavitation describes the collapse of a cavity bubble. [5] If the developed cavities fall apart, the effect on the stratum corneum lipids will increase the permeability of the skin. [6] [3] These areas of increased permeability are often called localized transport regions, where there is lower electrical resistivity. [8] One potential method is to use cavitation seed at the surface of the skin. [9] Another potential method is to use ultrasound-responsive liquid-core nuclei (URLN). [3]
Low-frequency ultrasound is seen as the optimal level of ultrasound frequency. This is typically characterized as 20 to 100 kHz (sometimes 18 to 100 kHz). [4] Low frequency makes cavitation more likely. For reference, high frequency ultrasound is typically in the range of 1 to 3 MHz. [5]
The drug should be able to work together with the coupling agent. [6] In a 2019 study, they used the drug diclofenac in coordination with thiocolchioside gel to treat patients who suffer from acute lower back pain. [10] An application of a drug serving as a coupling agent is the use of piroxicam gel mixtures and dexamethasone sodium phosphate gel mixtures to treat patients who suffer from carpal tunnel syndrome. [11]
Various conditions that can be addressed include cervical spine pain, [12] acute lower back pain, [10] carpal tunnel syndrome, [11] muscle injury, [13] rheumatoid arthritis, [14] and venous thrombosis. [2] Examples of drugs that have been used with sonophoresis include hydrocortisone, mannitol, dexamethasone, and lidocaine. [6]
Several products have been marketed to use phonophoresis for transdermal drug delivery. [6]
A potential future application of phonophoresis is to use it with vaccines, as phonophoresis is considered a less painful alternative to needles. [8] [6] [4] [1] Another potential use is in cancer therapeutics; one such application that has been explored is the delivery of cisplatin for patients who have cervical cancer. [15] Genetic skin diseases and wound healing may be assisted by phonophoresis. [6]
At an optimal frequency, phonophoresis will be painless and have minimal to no risk. The heat that is emitted from ultrasound use can also be damaging to the surface of the skin, [7] and cavitation can potentially lead to tissue damage. [7] Nanoparticle toxicity is another potential risk. [7]
Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN), it forms a spectrum of disease, with SJS being less severe. Erythema multiforme (EM) is generally considered a separate condition. Early symptoms of SJS include fever and flu-like symptoms. A few days later, the skin begins to blister and peel, forming painful raw areas. Mucous membranes, such as the mouth, are also typically involved. Complications include dehydration, sepsis, pneumonia and multiple organ failure.
In pharmacology and toxicology, a route of administration is the way by which a drug, fluid, poison, or other substance is taken into the body.
Iontophoresis is a process of transdermal drug delivery by use of a voltage gradient on the skin. Molecules are transported across the stratum corneum by electrophoresis and electroosmosis and the electric field can also increase the permeability of the skin. These phenomena, directly and indirectly, constitute active transport of matter due to an applied electric current. The transport is measured in units of chemical flux, commonly μmol/(cm2*hour). Iontophoresis has experimental, therapeutic and diagnostic applications.
An infantile hemangioma (IH), sometimes called a strawberry mark due to appearance, is a type of benign vascular tumor or anomaly that affects babies. Other names include capillary hemangioma, strawberry hemangioma, strawberry birthmark and strawberry nevus. and formerly known as a cavernous hemangioma. They appear as a red or blue raised lesion on the skin. Typically, they begin during the first four weeks of life, growing until about five months of life, and then shrinking in size and disappearing over the next few years. Often skin changes remain after they shrink. Complications may include pain, bleeding, ulcer formation, disfigurement, or heart failure. It is the most common tumor of orbit and periorbital areas in childhood. It may occur in the skin, subcutaneous tissues and mucous membranes of oral cavities and lips as well as in extracutaneous locations including the liver and gastrointestinal tract.
Placenta praevia is when the placenta attaches inside the uterus but in a position near or over the cervical opening. Symptoms include vaginal bleeding in the second half of pregnancy. The bleeding is bright red and tends not to be associated with pain. Complications may include placenta accreta, dangerously low blood pressure, or bleeding after delivery. Complications for the baby may include fetal growth restriction.
High-intensity focused ultrasound (HIFU) is a non-invasive therapeutic technique that uses non-ionizing ultrasonic waves to heat or ablate tissue. HIFU can be used to increase the flow of blood or lymph or to destroy tissue, such as tumors, via thermal and mechanical mechanisms. Given the prevalence and relatively low cost of ultrasound generation mechanisms, The premise of HIFU is that it is expect a non-invasive and low-cost therapy that can at minimum outperform operating room care.
Sonophoresis also known as phonophoresis, is a method that utilizes ultrasound to enhance the delivery of topical medications through the stratum corneum, to the epidermis and dermis. Sonophoresis allows for the enhancement of the permeability of the skin along with other modalities, such as iontophoresis, to deliver drugs with lesser side effects. Currently, sonophoresis is used widely in transdermal drug delivery, but has potential applications in other sectors of drug delivery, such as the delivery of drugs to the eye and brain.
Transdermal is a route of administration wherein active ingredients are delivered across the skin for systemic distribution. Examples include transdermal patches used for medicine delivery. The drug is administered in the form of a patch or ointment that delivers the drug into the circulation for systemic effect.
Therapeutic ultrasound refers generally to any type of ultrasonic procedure that uses ultrasound for therapeutic benefit. Physiotherapeutic ultrasound was introduced into clinical practice in the 1950s, with lithotripsy introduced in the 1980s. Others are at various stages in transitioning from research to clinical use: HIFU, targeted ultrasound drug delivery, trans-dermal ultrasound drug delivery, ultrasound hemostasis, cancer therapy, and ultrasound assisted thrombolysis It may use focused ultrasound (FUS) or unfocused ultrasound.
Sonoporation, or cellular sonication, is the use of sound in the ultrasonic range for increasing the permeability of the cell plasma membrane. This technique is usually used in molecular biology and non-viral gene therapy in order to allow uptake of large molecules such as DNA into the cell, in a cell disruption process called transfection or transformation. Sonoporation employs the acoustic cavitation of microbubbles to enhance delivery of these large molecules. The exact mechanism of sonoporation-mediated membrane translocation remains unclear, with a few different hypotheses currently being explored.
Pulsed electromagnetic field therapy, also known as low field magnetic stimulation (LFMS) is the use of electromagnetic fields in an attempt to heal non-union fractures and depression. By 2007 the FDA had cleared several such stimulation devices.
Sonodynamic therapy (SDT) is a noninvasive treatment, often used for tumor irradiation, that utilizes a sonosensitizer and the deep penetration of ultrasound to treat lesions of varying depths by reducing target cell number and preventing future tumor growth. Many existing cancer treatment strategies cause systemic toxicity or cannot penetrate tissue deep enough to reach the entire tumor; however, emerging ultrasound stimulated therapies could offer an alternative to these treatments with their increased efficiency, greater penetration depth, and reduced side effects. Sonodynamic therapy could be used to treat cancers and other diseases, such as atherosclerosis, and diminish the risk associated with other treatment strategies since it induces cytotoxic effects only when externally stimulated by ultrasound and only at the cancerous region, as opposed to the systemic administration of chemotherapy drugs.
Nanoparticles for drug delivery to the brain is a method for transporting drug molecules across the blood–brain barrier (BBB) using nanoparticles. These drugs cross the BBB and deliver pharmaceuticals to the brain for therapeutic treatment of neurological disorders. These disorders include Parkinson's disease, Alzheimer's disease, schizophrenia, depression, and brain tumors. Part of the difficulty in finding cures for these central nervous system (CNS) disorders is that there is yet no truly efficient delivery method for drugs to cross the BBB. Antibiotics, antineoplastic agents, and a variety of CNS-active drugs, especially neuropeptides, are a few examples of molecules that cannot pass the BBB alone. With the aid of nanoparticle delivery systems, however, studies have shown that some drugs can now cross the BBB, and even exhibit lower toxicity and decrease adverse effects throughout the body. Toxicity is an important concept for pharmacology because high toxicity levels in the body could be detrimental to the patient by affecting other organs and disrupting their function. Further, the BBB is not the only physiological barrier for drug delivery to the brain. Other biological factors influence how drugs are transported throughout the body and how they target specific locations for action. Some of these pathophysiological factors include blood flow alterations, edema and increased intracranial pressure, metabolic perturbations, and altered gene expression and protein synthesis. Though there exist many obstacles that make developing a robust delivery system difficult, nanoparticles provide a promising mechanism for drug transport to the CNS.
Timothy Grant Leighton is the Professor of Ultrasonics and Underwater Acoustics at the University of Southampton. He is the inventor-in-chief of Sloan Water Technology Ltd., a company founded around his inventions. He is an academician of three national academies. Trained in physics and theoretical physics, he works across physical, medical, biological, social and ocean sciences, fluid dynamics and engineering. He joined the Institute of Sound and Vibration Research (ISVR) at the University of Southampton in 1992 as a lecturer in underwater acoustics, and completed the monograph The Acoustic Bubble in the same year. He was awarded a personal chair at the age of 35 and has authored over 400 publications.
Joseph Kost is an Israeli academic, currently holder of The Abraham and Bessie Zacks Chair in Biomedical Engineering and the past Dean of the Faculty of Engineering Sciences at the Ben-Gurion University of the Negev.
Mark Robert Prausnitz is an American chemical engineer, currently Regents’ Professor and J. Erskine Love, Jr. Chair in Chemical & Biomolecular Engineering at the Georgia Institute of Technology. He also serves as adjunct professor of biomedical engineering at Emory University and Adjunct Professor of Chemical & Biomolecular Engineering at the Korea Advanced Institute of Science and Technology. He is known for pioneering microneedle technology for minimally invasive drug and vaccine administration, which has found applications in transdermal, ocular, oral, and sustained release delivery systems.
Focused ultrasound for intracrainial drug delivery is a non-invasive technique that uses high-frequency sound waves to disrupt tight junctions in the blood–brain barrier (BBB), allowing for increased passage of therapeutics into the brain. The BBB normally blocks nearly 98% of drugs from accessing the central nervous system, so FUS has the potential to address a major challenge in intracranial drug delivery by providing targeted and reversible BBB disruption. Using FUS to enhance drug delivery to the brain could significantly improve patient outcomes for a variety of diseases including Alzheimer's disease, Parkinson's disease, and brain cancer.
Penetration enhancers are chemical compounds that can facilitate the penetration of active pharmaceutical ingredients (API) into or through the poorly permeable biological membranes. These compounds are used in some pharmaceutical formulations to enhance the penetration of APIs in transdermal drug delivery and transmucosal drug delivery. They typically penetrate into the biological membranes and reversibly decrease their barrier properties.
Ultrasound-triggered drug delivery using stimuli-responsive hydrogels refers to the process of using ultrasound energy for inducing drug release from hydrogels that are sensitive to acoustic stimuli. This method of approach is one of many stimuli-responsive drug delivery-based systems that has gained traction in recent years due to its demonstration of localization and specificity of disease treatment. Although recent developments in this field highlight its potential in treating certain diseases such as COVID-19, there remain many major challenges that need to be addressed and overcome before more related biomedical applications are clinically translated into standard of care.
Ultrasound assisted extraction (UAE) is the process of passing waves of ultrasonic energy through a liquid solvent containing solid particles. A force parallel to or perpendicular to the material's surface is produced as the waves collide with it.
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