Chemotherapy drugs in microcapsules

A microparticle-based chemopreparation delivery system has been created

Anna Stavina, XX2 century

Chemists from the University of Alabama at Birmingham have developed new microcapsules for chemotherapeutic drugs. Perhaps, thanks to this invention, targeted drug delivery will approach preclinical trials.

Multi-layer capsules have three advantages, which could not be combined in one object before. Firstly, the capsules have high contrast, so they are easy to observe with low-power ultrasound. Secondly, these shells are able to reliably and stably retain the drug doxorubicin, used for the treatment of many types of oncological diseases. And, finally, thirdly, capsules can be destroyed by both low–power and massive ultrasonic wave - this will lead to the release of the drug.

Drawing from the press release of UAB creates triple-threat cancer-fighting polymer capsules
for guided drug delivery – VM

The therapeutic effectiveness of the new development can be improved by modifying the surface of the capsules and increasing the accuracy of targeting. After that, doctors will be able to use an ultrasound diagnostic device to observe how nanocapsules are concentrated in the focus of the disease. Then, with the help of a more powerful pulse, the therapeutic ultrasound device will cause tiny "bombs" to discharge directly at the destination, protecting the rest of the body from the negative effects of doxorubicin or other chemotherapeutic agent. Thanks to the new system, it may be possible to overcome the limitations imposed on the dosage of the drug by its toxicity.

Since the developed delivery method will allow doctors to accurately determine the place and time of exposure to the tumor, over time this approach will be able to replace conventional surgery or systemic chemotherapy. This is reported by the authors of a study published in ACS Nano (Chen et al., Theranostic Multilayer Capsules for Ultrasound Imaging and Guided Drug Delivery).

"We decided to create a fundamentally new approach to the treatment of dense tumors of various subtypes, including metastatic lesions caused by bowel, breast, prostate or lung cancer, as well as melanomas. These capsules will be used as a delivery system," says Evgenia Kharlampieva, associate professor of chemistry at the University of Alabama. "They can protect the drug from recycling or premature leaching from the body."

Kharlampieva created "smart" particles, working at the junction of several fields of science: polymer chemistry, nanotechnology and biomedicine. According to the scientist, there is currently a huge, still unsatisfied need for managed drug delivery systems that would be easy to manufacture.

The new capsules consist of alternating layers of biocompatible tannin and poly-n-vinylpyrrolidone. The layers wrap around a core of silicon or porous calcium carbonate, which dissolves after the capsule is formed. By controlling the number of layers, the molecular weight of the polymer and the ratio of the thickness of the capsule and its diameter, scientists were able to change the physical properties of the particles and their sensitivity to ultrasound. Thanks to this, now the power required for splitting the ultrasonic wave capsule does not exceed the maximum permissible values.

To find out how well the particles will be displayed on the ultrasound scanner screen, the researchers created capsules with a diameter of 5 microns. Particles of this size could pass through the pulmonary capillaries – the diameter of red blood cells, for comparison, is from 6 to 8 microns. Larger particles would have greater contrast, but would hardly be able to solve the problem of delivering the drug directly to its destination. It turned out that empty capsules with a diameter of 5 microns, made of 8 layers of tannin and a "light" polymer, are comparable in contrast with the distributed contrast material based on Definity microspheres. And when doxorubicin was placed in the capsules, the contrast – depending on the scanner used – increased 2-8 times.

Microspheres with doxorubicin turned out to be extremely stable – their ability to be displayed on the ultrasound device screen did not change even after 6 months of storage.

The ultrasound wave of therapeutic power was able to destroy 50% of capsules filled with the drug with a diameter of 5 microns. The drug released in this case was enough to provide 97% cytotoxicity in human breast adenocarcinoma cell culture. Adenocarcinoma cells that were grown in the same container with intact microcapsules filled with doxorubicin remained alive.

Thus, according to Kharlampieva, the new development in combination with ultrasound has a significant "theranostic" potential. Using this term, the scientist designated the dual purpose of capsules – they are both a therapeutic agent and a diagnostic contrast agent. The next step of scientists will be the study of capsules on animal models. It is necessary to find out how long the particles remain in the blood and how they spread through the body.

Portal "Eternal youth" http://vechnayamolodost.ru  03.04.2017