Use of ultrasound in drug delivery systems: emphasis on experimental methodology and mechanisms

Figures & data

Figure 1. In vitro set up for sonication experiments. (A) A dish containing the sample (S) is positioned directly on top of the transducer (T) after applying acoustic gel to avoid air between the transducer and the dish. (B) Ultrasound travels horizontally through degassed distilled water to irradiate the sample positioned at a certain distance. At the far end is an ultrasound absorber (UA) that prevents reflection of ultrasound. (C) The tube containing the sample is positioned a few centimeters from the transducer and could be rotated during sonication for a more uniform exposure of its content. Ultrasound is directed upwards to hit the sample. (D) For small samples (such as those using 24 or 96 well plates), small transducers (e.g. less than 10 mm in diameter) can be dipped directly into the sample for sonication.

Table 1.  Advantages and disadvantages among experimental systems

Experimental system	Advantages	Disadvantages
Basic in vitro (See Figure 1 for sample set-ups)	• Generally easy to design • Economical • Suitable for processing large number of samples • Easy to do assay for drug delivery experiments on cultured cells	• Less reproducible in vivo • Set-ups are usually varied • Acoustic factors may be difficult to control
Ex vivo	• Less expensive than in vivo • In vitro or in vivo-simulated set-ups used for cell culture experiments may be applied in this system	• Some surgical skills may be required • Assays for cells experiments may not be suitable • Drug delivery may be difficult to quantify
In vivo-simulated (See Figure 2 for an example set-up)	• Greater reproducibility in vivo • Less expensive than in vivo • May use cultured cells for drug delivery experiments	• Generally difficult to design • May not be suited for large number of samples
In vivo	• Experimental design and results could be useful to design protocol for eventual clinical trials	• Can be expensive • More time may be needed before getting the end results • Limited options for assays to evaluate drug delivery experiments

Figure 2. In vivo-simulated set up. This is a novel in vitro set-up that simulates in vivo conditions. Close chamber containing cancer cells is sandwiched in between transmitting oil simulating soft tissue in the body and ultrasound absorber on the opposite side to minimize reflection of ultrasound waves.

Figure 3. Targeted drug delivery by ultrasound with microbubbles. Microbubbles can be engineered to carry therapeutic agents and at the same time carry with them ligands that specifically latches on to particular cells (e.g. cancer cells belonging to a cancer cell line). Conceptually, these engineered microbubbles will be injected intravenously into a cancer patient, allowing time for the microbubble to localize on the cancer cells before sonication. Sonication will release and deliver the therapeutic agent into the target cells. Ultrasound in this case should reach an acoustic pressure sufficient to destroy the bubbles, but may generate mechanical and thermal effects in the surrounding tissue without or with fewer microbubbles and less drug. The expected effect would be greater on the target cells and tissues, with minimal side effects.