Interview with representative from "Petru Poni" Institute of Macromolecular Chemistry
1. What kind of activities does the "Petru Poni" Institute carry out?
Within this project, we dealt with the design and production of nanostructures to carry out the transport of drugs in the tumor tissue.
2. What is the technology of anticancer drugs based on micellar constructions?
Anticancer drug technology based on pH-dependent micellar constructs represents a promising approach in the development of cancer treatments. This technology involves the use of micelles, which are spherical aggregates of amphiphilic molecules (molecules with a hydrophobic and a hydrophilic part) to transport and release drugs in a specific way to tumor areas. Micelles show different properties depending on the pH of the environment around them. These assemblies can undergo a structural change in response to variations in pH. They are usually stable at higher pH, such as normal plasma pH, but may disaggregate at lower pHs, such as those in the tumor environment. A key feature of this technology is the ability to specifically target tumor tissues. Due to the characteristic pH changes in the tumor environment (lower pH), the pH-dependent micelles can release drugs selectively within the tumor. This helps minimize drug exposure to healthy tissues and maximize treatment effectiveness. Micellar technology can be used to transport a variety of anticancer drugs, including chemotherapeutic agents and biologically targeted drugs such as monoclonal antibodies. This technology is constantly developing, and researchers are exploring different types of micellar assemblies, drugs, and delivery strategies to improve the efficacy of anticancer treatments based on pH-sensitive micelles.
Our concept is based on the use of specific extratumoral pH values as a trigger for localized and targeted delivery of modular nanoassemblies based on polyhistidine-polyethylene glycol copolymers capable of self-assembling into micelles or vesicles.
3. What is the difference between medicines based on micellar assemblies and existing ones?
Medicines based on micellar assemblies present several significant differences compared to traditional medicines on the market. One of the main differences is the ability of micellar assemblies to accumulate and release drugs specifically in tumor areas. Due to the pH-shifting reaction characteristic of the tumor environment, these assemblies can be designed to release drugs only in cancer-affected tissues, thus minimizing the exposure of healthy tissues to the drug. Also, drugs based on micellar assemblies can provide a controlled and gradual release of the drug over time. Because drugs are delivered more precisely to target tissues and are protected by micellar assemblies during transport, this can lead to reduced toxicity to healthy tissues in the body.
4. What is the main index/substance/criterion in the medicine based on micellar assemblies?
The system we developed represents an innovative approach to cancer treatment, based on the use of micellar assemblies modified with Trastuzumab. This strategy allows us to have precise control over the delivery of the drug and obtain a double benefit: both the specific targeting of cancer cells and the direct therapeutic effect on them.
Trastuzumab is a monoclonal antibody recognized for its ability to bind to HER2 receptors on the surface of cancer cells, particularly in HER2-positive breast cancer. It acts as a targeting agent, guiding micellar assemblies to tumor areas, where HER2 receptors are overexpressed.
In addition to its role as a targeting agent, Trastuzumab can also have a direct therapeutic effect on cancer cells, inhibiting their proliferation and survival. Therefore, the combination with micellar assemblies loaded with cancer cell-specific AXL inhibitors represents a smart strategy to address several aspects of tumor development.
AXL inhibitors are compounds that specifically target the AXL receptor, which is often overexpressed in cancer and may play an important role in tumor progression and metastasis. By delivering these inhibitors using micellar assemblies to the tumor site, we can interfere with the survival and proliferation mechanisms of cancer cells, helping to shrink the tumor and slow its spread.
5. What is the path of innovative medicines from manufacturers to patients?
The journey of innovative medicines from manufacturers to patients is a complex and rigorous process involving several critical stages, including research, development, testing, regulatory approval and distribution. It can take years and involve significant development and production costs. It is a complex and strictly regulated process to ensure the safety and effectiveness of innovative medicines. Regulatory authorities and health organizations play a critical role in evaluating, approving and monitoring these drugs to protect public health.
6. How long does it take to introduce a new innovative drug to the market?
The time it takes to bring an innovative new drug to market can vary significantly and can take anywhere from 10 to 15 years or even longer. The process is complex and involves several steps, each with strict testing and regulatory requirements.
7. What is the stage of preparation of the proposed system within the project you are coordinating?
Currently, the system we developed has gone through a detailed characterization and testing process, demonstrating its effectiveness at various stages of development. Our system was subjected to rigorous characterization to understand in detail the structure and behavior of micellar assemblies decorated with Trastuzumab and loaded with AXL inhibitors. This step was essential to ensure optimal control over the drug delivery process.
We performed in vitro tests using breast cancer cell lines. These tests demonstrated the ability of the system to specifically target these cancer cells and exert an effective therapeutic effect on them. The positive results obtained in the cell culture medium confirmed the therapeutic potential of the system.
We advanced the development process by testing our system in animal models, specifically mice. These in vivo studies have shown success in targeting and shrinking breast cancer tumors. This step is particularly significant because it reflects the behavior of the system in a more complex environment, similar to that of the human body.
These positive results in our in vitro and in vivo studies represent a significant advance in the development of our system. They highlight the system's potential to provide an effective and targeted therapeutic option for breast cancer patients and pave the way for further advancement in its development and testing in clinical stages.
8. What are the prospects for implementation?
The prospects for the implementation of the previously discussed systems based on the micellar assemblies modified with Trastuzumab and loaded with AXL inhibitors for the treatment of breast cancer are promising and may provide significant benefits in the medical field. One of the next important steps is the further development of the system and the transition to clinical stages. This involves testing on human patients to assess the safety and efficacy of the system in a clinical setting. If the clinical results are positive, the system could become a viable treatment for breast cancer patients.
9. Are innovative medicines based on micellar assemblies more expensive than existing ones?
The cost of innovative drugs, such as those based on micellar assemblies decorated with Trastuzumab and loaded with AXL inhibitors, can vary considerably and be higher than that of existing drugs on the market. There are several reasons for this: the process of developing innovative drugs involves extensive research and expensive clinical trials over many years. This can generate significant costs, and these costs can be reflected in the final price of the drug.
Pharmaceutical companies that develop innovative drugs generally obtain patents for these drugs, which give them market exclusivity for a certain period of time (usually 20 years). During this period, they can charge higher prices to recoup their investment and make a profit.
Breakthrough drugs may involve new technologies or complex manufacturing procedures, which may increase manufacturing costs. Although innovative drugs may be more expensive, they can offer significant benefits in terms of efficacy, reduced side effects, or the treatment of conditions that previously had no adequate therapeutic options. These benefits may justify the higher costs for some patients.
10. What are the risks generated by medicines based on micellar assemblies compared to existing ones?
Drugs based on micellar assemblies, such as those decorated with Trastuzumab and loaded with AXL inhibitors, may present specific risks and differences compared to existing drugs. It is important to consider these aspects. Certain components of micellar assemblies or the drug may trigger hypersensitivity reactions in some patients. This may include severe allergic reactions that require immediate treatment.
Micellar assemblies are delicate structures and can be sensitive to temperature or pH variations. This may influence the stability of the medicine and may require special storage or handling conditions.
Due to the complexity of micellar assemblies, they can interact with other drugs a patient is taking, altering their effects or toxicity. It is important for the doctor to be aware of all the medications a patient is taking to avoid such interactions.
11. Are there any important adverse reactions?
It is true that at the current stage of development of new systems, such as those based on micellar assemblies, it is difficult to fully anticipate all possible side effects. Usually, side effects are better understood and documented during clinical trials, when the drug is tested on a larger number of patients. Clinical trials are essential steps in drug development because they provide the opportunity to evaluate the drug's safety and effectiveness on larger groups of patients under the close supervision of medical experts. As clinical trials progress, a safety and efficacy profile is developed for the drug, which provides detailed information on side effects, their frequency, and their severity. It is important to emphasize that, in most cases, the therapeutic benefits of a drug are weighed against the potential risks of side effects. In the case of innovative medicines, they can bring significant benefits, but it is essential to continue monitoring and reporting side effects to ensure an appropriate balance between efficacy and safety in the treatment of patients.