How non-invasive methods of drug administration work: nano-delivery of drugs, hydrogels and nano-plasters

All modern non-invasive methods of drug administration, as a rule, are a system of target

delivery of pharmaceuticals. This means selective transportation of drugs or substances to the necessary tissues, organs and cells through various carrier vehicles. Such mechanisms improve the pharmacological and therapeutic properties of conventional drugs and overcome such problems as limited solubility, drug aggregation, insufficient distribution of the drug in the tissues and the inability to choose a point treatment area, control the elimination of the drug and reduce damage to neighboring cells. Non-invasive methods can increase the time of exposure of the drug at the site of injury and introduce the optimal concentration of the substance.

Nanodelivery and hydrogels

System nanomedicine and nanodelivery -relatively new, but rapidly developing branch of science. Materials in the nanoscale range are used as diagnostic tools or for the delivery of therapeutic agents targeted, to the necessary organ, under the close supervision of a physician. Nanotechnology has many advantages in the treatment of chronic human diseases with the help of specific and targeted drug delivery.

Natural compounds have already shown their higheffective in treating cancer, diabetes, cardiovascular, inflammatory and microbial diseases. This is mainly due to the fact that drugs based on natural ingredients have lower toxicity and side effects, are relatively inexpensive and demonstrate good therapeutic potential.

However, issues related to biocompatibilitynatural compounds are a big problem when used as medicines. Consequently, many natural compounds do not undergo a clinical trial filter solely for these reasons. The introduction of drugs into the body through injections or using conventional film-coated tablets creates serious problems, including instability in vivo, poor bioavailability and solubility, insufficient absorption in the body, as well as possible side effects of drugs.

In vivo (from an armor. - "in (on) live") - “inside a living organism” or “inside a cell”.

In in vivo science means conducting experimentson (or inside) living tissue in vivo. Such use of the term excludes the use of a part of a living organism (as it is done in vitro tests) or the use of a dead organism. Animal testing and clinical trials are forms of in vivo research.

Neither injections nor pills guarantee hitmedication in the required organ or area. Consequently, the use of new drug delivery systems to target specific parts of the body may be an option that can solve these critical problems. Nanotechnology plays an important role in advanced drugs aimed at controlled release of drugs inside the body.

Why taking pills sometimes does not improve the patient's condition at all?

The first reason is pretty commonplace - somemedications work best when taken at a specific time of the day or with meals. People may simply forget to take the medicine on time or not pay due attention to the instructions of the doctor about the time of taking the drugs, which is not an empty whim of the therapist. In addition, even a parallel intake of vitamins or dietary supplements can affect the rate of absorption and other medications taken. In addition, patients are sometimes negligent of the recommended diet and do not follow it, despite the fact that the products can affect how the body takes the medications or how they work. Hormonal problems, poor metabolism, poor sleep, high blood pressure or unstable work of the gastrointestinal tract can also change the effect of drugs, so before prescribing drugs the doctor always asks the patient questions regarding his general condition. Any of the above problems can be considered a significant reason for changing the treatment regimen or the dosage of the prescribed drug.

Recent studies have shown that materials inhydrogel form can be used to deliver various drugs and substances through the stomach to a more alkaline environment. Hydrogels are three-dimensional, polymeric networks that are considered highly permeable to various medicinal compounds, can resist an acidic environment and swell, thereby releasing trapped molecules through their mesh surfaces.

Hydrogel, created at the Massachusetts Institute of Technology. Photo: MIT

Depending on the chemical composition of the gelVarious internal and external stimuli (for example, changes in pH, application of a magnetic or electric field, changes in temperature and ultrasonic radiation) can be used to trigger this effect. However, after this, the rate of captured drug release is determined solely by the crosslinking coefficient of the polymer network.

Over the past two decades of researchHydrogel delivery systems have focused primarily on systems containing the main chains of polyacrylic acid (PAA). PAA hydrogels are known for their superabsorbing ability and ability to form long polymer networks by means of hydrogen bonds. In addition, they have the qualities of excellent natural adhesives. This means that they can stick to the mucous membrane of the gastrointestinal tract for a long period of time, slowly releasing the encapsulated drugs.

Adhesive - a substance capable of combining materials bysurface clutch. Adhesives are natural and synthetic. The adhesive action of the adhesive is based on the creation of molecular bonds between it and the surfaces of the materials being joined. Microscopic irregularities filled with adhesive, increase the contact area between adjacent surfaces. After curing the adhesive, they stick together.

In 1997, chemical engineers from the UniversityPurdue in West Lafayette, Indiana, under the direction of Nicholas A. Peppas, reported on the synthesis of a glucose-sensitive hydrogel that can be used to inject insulin into diabetic patients using an internal pH trigger. This system has an insulin-containing "reservoir" formed by a hydrogel membrane in which glucose oxidase was placed.

Unlike hydrogel systems thatsecrete trapped medicinal substances when swelling, this system works in the opposite way, compressing the membrane "gates". The exact trigger for this mechanism involves creating an acidic environment around the gel. This is achieved when the body produces high levels of sugar; glucose interacts with immobilized glucose oxidase at the gate, forming gluconic acid, which, in turn, lowers the body's pH and causes the gate to open. Thus, your own glucose levels determine and guide the delivery of insulin. Researchers are currently studying ways to accurately control the speed of drug delivery, considering the effects of varying gate size, trapped insulin concentration, and the speed at which the gate can open and close.

Tablets on a string

The task in the development of delivery systemsmedicines for treating diseases such as tuberculosis, is to balance the simplicity and safety of administration and optimize the dosage of drugs at several levels. During the intensive treatment phase, a 60-pound tuberculosis patient swallows nearly 100 g of antibiotics per month. Taking the medication through the gastrointestinal tract provides many benefits, including ease of administration, immuno-tolerance to a wide range of materials, and the ability to optimize the dosage with an accuracy of one gram in accordance with existing tuberculosis treatment regimens.

Development of an acid resistant systemstomach (GRS, Gastric resistant system - “High-tech”), is conducted in order to ensure that patients who need daily medication, timely and complete treatment. Tablets, literally strung on a superstable material - nitinol wire, are inserted through the nose with a tube, which after the location of the system is taken out. GRS is in the gastric cavity all the prescribed time for taking drugs, medicinal substances are systematically absorbed through the walls of the stomach. After completion of treatment, the patient is again placed a tube, at the end of which there is a search device for attaching and removing the GRS from the cavity of the stomach. The search device consists of a sensor and a magnet that can detect and attach to magnets at either end of the GRS. The dotted circles in the picture below indicate the linkage of the search device with the GRS. The components of both ends of the GRS are also shown - glue, retainer and a cap of polycaprolactone.

GRS due to superelasticity of nitinol cancurl back to its original spiral shape for a compact arrangement in the gastric cavity after passing through the esophagus, which should help avoid the feeling of foreignness and discomfort in patients The system was tested on pigs weighing from 30 to 75 kg. After a long stay of the system in the stomach on the mucous membranes of the stomach of animals there was no damage, erosion or ulceration. In addition, they did not experience weight loss, signs of obstruction of the gastrointestinal tract or restrictions in the passage of food or fluids. Tablets for the system are made by mixing drugs with silicones, in addition, they are coated with a polymer coating. The diameter of each tablet is 4 mm.

Sidebar

Scientists have high hopes for this system.as a means of combating tuberculosis, primarily through the DOTS program. In 1994, WHO endorsed the Direct Observation Strategy with the Short Course of Treatment (DOTS), which is currently adopted worldwide. DOTS includes taking oral combination anti-TB drugs at a particular clinic in the presence of a health professional every day or three times a week. Currently, achieving the desired results requires a substantial infrastructure with properly staffed medical staff, but GRS does not require weekly in-patient monitoring.

"Hightech" already wrote about how the groupResearchers from the University of California presented the development of a reactive tablet, which with the help of titanium dioxide and magnesium nanoparticles will deliver drugs.

Innovative methods of cancer diagnosis and treatment

  • Liquid biopsy. Scientists from universities of California and Sun Yatsenhave developed a new method for diagnosing liver cancer. This method is based on the detection of tumor DNA in a blood test. Liquid biopsies will detect fragments of the genetic material of a tumor that has entered the blood. Such biopsies are minimally invasive and allow doctors to track molecular changes in a tumor in real time. You can identify a tumor that is not yet visible on an MRI. In addition, through such a study, you can find out exactly whether this tumor is malignant or not. A conventional biopsy can only answer this question about a particular piece of tumor taken for analysis. In their study, researchers analyzed hundreds of thousands of blood samples from healthy people and patients suffering from liver cancer. They were able to identify the specific composition of methylation markers inherent in this particular oncological disease. DNA methylation is a process that can regulate gene generation. Increased methylation of tumor suppressor genes is a clear sign that a tumor has appeared in the body.
  • Nanomachines delivering medicine in the treatment of cancer in the brain. To develop reactive cancer treatmentsResearch is also being conducted in the field of gene therapy, which is aimed at reducing the genetic causes of diseases. Scientists focus on the principle of introducing a drug based on nucleic acid into the bloodstream — a small interfering RNA that binds to a specific gene causing problems and deactivates it. Modern nanoparticles are about 100 nm wide, but for some cancers they are too large to reach the goal. Cancer of the pancreas is surrounded by fibrous tissues, and cancer of the brain is tightly connected by vascular cells. In both cases, the available gaps are much smaller than 100 nm. Scientists have already created a fairly compact RNA carrier that can penetrate through these gaps in tissues.
  • Implant for cancer treatment. The MIT and Central Research GroupMassachusetts Hospital has developed an implant for the introduction of chemotherapy drugs directly into the tumor of the pancreas. Injections of chemotherapy drugs do not always give results, because the tumor contains few blood vessels and is located deep enough - the medicine needs to pass too many barriers to the goal. In addition, the pancreas is surrounded by a thick, wiry layer that prevents the penetration of drugs. A PLGA film, developed by scientists, is rolled into a thin tube and inserted into a catheter, after which it is implanted. When the film reaches the gland, it unfolds and adapts to the shape of the tumor. Medicines applied to the film begin to act after a specified period of time. The reverse side of the implant is not covered by them to minimize unwanted side effects.

Nano-plasters

In January 2019, David Hoy, GeneralDirector of Vaxxas, spoke about the work on improving the effectiveness of vaccines using a new technology for delivering vaccines called Nanopatch (nano-plaster - "High-tech"). The principle of Nanopatch is to use thousands of microneedles in one small area, which perforate the outer layers of the skin without serious consequences. At the ends of the Nanopatch microneedles, the scanty substance of the vaccine, which reacts with immune cells directly beneath the surface of the skin. This allows you to effectively deliver antigens to the lymph nodes for a quick immune response. During animal tests, it was proved that only from 1/10 to 1/100 of the current dose of the vaccine, which entered the body using a nano-plaster, can trigger an immune response equivalent to a full dose, with a syringe injection. In addition to this, the vaccines applied to the nanopayment can be designed so that they do not require special storage conditions, and this is a huge potential victory for the markets of developing countries. In addition, to get a vaccine from a nano-plaster, you will not have to resort to the help of health workers, the method of its use is so simple that it can be used at home.

Nano plaster

Researchers have suggested using microneedlesto deliver to the retina patients who are at risk of losing sight due to its detachment, a drug that can prevent this process is lucentis. The needles will dissolve within just 30 seconds, and the patient will not experience pain.

Also nanoplastic technology can be usedas a contraceptive. The microneedles of a nanoplaster are made of polymers, and they contain levonorgestrel as an active substance. The components of microneedles gradually dissolve in the blood and within a month protect from unwanted pregnancy.

Perhaps soon our future is drasticallywill change. We will be treated completely differently - the nanotubes will deliver drugs directly to the stomach or in the form of hydrogel-based preparations, and we will vaccinate ourselves at home. Despite this, it will still be important to monitor your health, consult a doctor in a timely manner and not just rely on new medical technologies.