Ultrasounds for Improving Drug Delivery
Reporter: Danut Dragoi, PhD
Using the property of sounds to proppagate in aqueous media, such that in human body, researcher from MIT and Massachusetts General Hospital (MGH) have found a way to enable ultra-rapid delivery of drugs to the gastrointestinal (GI) tract where this approach could make it easier to deliver drugs to patients suffering from GI disorders with inflammatory bowel disease, ulcerative colitis, and Crohn’s disease.
As we know from Physics the speed of sound in liquids, for example in water is 1,507 m/sec at 30 C degrees which is greater than that in air, 340m/sec, we can call them ultrasounds. Any sounds in human fluid or fluid composite carries on an accoustic energy that can excert a pressure or movement to any molecule of disolved drugg, that usually has a good solubility in water. If the molecules dissolved in GI truct that belongs to a specific drug are under a sonic field they can be moved accordingly, increasing the probability to get inside the targeted cells to be cured by that specific drug.
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http://news.mit.edu/2015/ultrasound-drug-delivery-inflammatory-bowel-disease-1021
Currently, GI diseases are usually treated with drugs administered as an enema, which must be maintained in the colon for hours while the drug is absorbed. However, this can be difficult for patients who are suffering from diarrhea and incontinence. To overcome that, the researchers sought a way to stimulate more rapid drug absorption. The novelty of drugg delivery efficiently using ultrasounds is that of an enhanced delivery.
Ultrasound improves drug delivery by a mechanism known as transient cavitation. When a fluid is exposed to sound waves, the waves induce the formation of tiny bubbles that implode and create micro-jets that can penetrate and push medication into tissue. In the study shown here , the researchers first tested their new approach in the pig GI tract, where they found that applying ultrasound greatly increased absorption of both insulin, a large protein, and mesalamine, a smaller molecule often used to treat colitis. In order to demonstrate a better treatment the researchers next investigated whether ultrasound-enhanced drug delivery could effectively treat disease in animals.
In tests of mice, the researchers found that they could resolve colitis symptoms by delivering mesalamine followed by one second of ultrasound every day for two weeks. Giving this treatment every other day also helped, but delivering the drug without ultrasound had no effect.
They also showed that ultrasound-enhanced delivery of insulin effectively lowered blood sugar levels in pigs.
It is worth mentioning that a modeling of ultrasound -induced micro-bubble oscillations in a capillary blood vessel exists here
in which a study is focused on the transient blood–brain barrier disruption (BBBD) for drug delivery applications.
In other studies, the ultrasound mediated drug delivery for cancer treatment is shown as a review of therapeutic ultrasound used to thermally ablate solid tumors since the 90s. A variety of cancers are presently being treated clinically, taking advantage of ultrasound- or MR-imaging guidance. A review summary of in vivo ultrasound-based strategies shows the deliver drug payloads to tumor environments, to enhance permeability of vessel walls and cell membranes, and to activate drugs and genes in situ.
An important physical effect of ultrasounds is their action decrease with the square distance from the source. In order to avoid increasing power of ultrasounds with negative effects on human body, the study shown in here considers the mechanisms responsible for how ultrasound and biological materials interact and how ultrasound-induced bio-effect or risk studies focus on issues related to the effects of ultrasound on biological materials. Whenever ultrasonic energy is propagated into an attenuating material such as tissue, the amplitude of the wave decreases with distance. The wave attenuation is due to either
- absorption
- or scattering
Absorption is a mechanism that represents that portion of ultrasonic wave that is converted into heat, and scattering can be thought of as that portion of the wave, which changes direction. Because the medium can absorb energy to produce heat, a temperature rise may occur as long as the rate of heat production is greater than the rate of heat removal. Current interest with thermally mediated ultrasound-induced bioeffects has focused on the thermal isoeffect concept. The non-thermal mechanism that has received the most attention is acoustically generated cavitation wherein ultrasonic energy by cavitation bubbles is concentrated. Acoustic cavitation, in a broad sense, refers to ultrasonically induced bubble activity occurring in a biological material that contains pre-existing gaseous inclusions. Cavitation-related mechanisms include radiation force, microstreaming, shock waves, free radicals, microjets and strain. It is more challenging to deduce the causes of mechanical effects in tissues that do not contain gas bodies.
SOURCE
[1] http://news.mit.edu/2015/ultrasound-drug-delivery-inflammatory-bowel-disease-1021
[2] https://www1.ethz.ch/ltnt/publications/Journal/pubimg/2012_Wiedemair1.pdf
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