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 targeted

delivery of pharmaceuticals.This means the selective transport of drugs or substances to the desired tissues, organs and cells through various carrier media. Such mechanisms improve the pharmacological and therapeutic properties of conventional drugs and overcome problems such as limited solubility, drug aggregation, insufficient drug distribution in tissues and lack of choice of targeted treatment area, control of drug elimination and reduction of damage to neighboring cells. Non-invasive methods can increase the time of exposure of the drug to the lesion site and introduce the optimal concentration of the drug.

Nanodelivery and hydrogels

Nanomedicine and nanodelivery system -a relatively new but rapidly developing branch of science. Materials in the nanoscale range are used as diagnostic tools or for the targeted delivery of therapeutic agents to the required organ, under the constant supervision of a physician. Nanotechnology has many advantages in treating chronic human diseases through specific and targeted drug delivery.

Natural compounds have already shown their higheffectiveness in the treatment of cancer, diabetes, cardiovascular, inflammatory and microbial diseases. This is mainly because 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 does taking pills sometimes not improve the patient’s condition at all?

The first reason is quite banal - somemedications work best when taken at certain times of the day or with meals. People may simply forget to take medications on time or not pay due attention to the doctor's instructions about when to take medications, which is not an idle whim of the therapist. In addition, even parallel intake of vitamins or dietary supplements can affect the rate of absorption of other medications taken. In addition, patients are sometimes careless about the recommended diet and do not follow it, despite the fact that the foods may affect how the body accepts medications or how they work. Hormonal problems, poor metabolism, poor sleep, high blood pressure or gastrointestinal instability can also change the effect of drugs, so before prescribing drugs, the doctor always asks the patient questions about his general condition. Any of the above problems may be considered a significant reason to change the treatment regimen or 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 into a more alkaline environment. Hydrogels are three-dimensional, polymeric networks that are considered to be highly permeable to various drug compounds and can withstand acidic environments and swell, thereby releasing trapped molecules through their network 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 joining materials bysurface adhesion. Adhesives can be natural or synthetic. The fastening effect of an adhesive is based on the creation of molecular bonds between it and the surfaces of the materials being joined. Microroughness filled with adhesive increases the contact area between adjacent surfaces. After the adhesive hardens, 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

Challenge when developing delivery systemsof drugs to treat diseases such as tuberculosis is to balance ease and safety of administration and optimize drug dosage at multiple levels. During the intensive phase of treatment, a 60-kg patient with tuberculosis ingests almost 100 g of antibiotics in a month. Taking drugs through the gastrointestinal tract offers many advantages, including ease of administration, immunotolerance to a wide range of materials, and the ability to optimize dosage down to the gram to match existing TB treatment regimens.

Development of a system resistant to acidic environmentsstomach (GRS, Gastric resistant system - Hi-Tech), is carried out in order to provide patients who need daily medication with timely and complete treatment. The tablets, literally strung on a super-resistant material - nitinol wire, are inserted through the nose using a tube, which is removed after positioning the system. GRS is in the gastric cavity during the entire prescribed time of taking the drugs; drugs are systematically absorbed through the walls of the stomach. After treatment is completed, the patient is placed back into a tube with a retrieval device at the end to attach and remove the GRS from the stomach cavity. 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 coupling of the search device with the GRS. Also shown are the components of both ends of the GRS - adhesive, retainer and polycaprolactone plug.

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.


Scientists have high hopes for this systemas a means of combating tuberculosis, primarily within the framework of the DOTS program. In 1994, WHO endorsed the direct observation short course (DOTS) strategy, which is now adopted worldwide. DOTS involves taking oral combination anti-TB drugs in a designated clinic with a health care professional every day or three times a week. Currently, significant infrastructure with adequately staffed medical personnel is required to achieve the desired results, but GRS does not require weekly hospital 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 that deliver drugs to treat 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.MIT and Central Research GroupMassachusetts General Hospital has developed an implant to inject chemotherapy drugs directly into a pancreatic tumor. Injections of chemotherapy drugs do not always work because the tumor contains few blood vessels and is located quite deep - the medicine must pass through too many obstacles on the way to its target. In addition, the pancreas is surrounded by a thick, sinewy layer that prevents the penetration of medications. The PLGA film developed by the 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 specified periods of time. The reverse side of the implant is not covered with them to minimize unwanted side effects.


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.