Translation. Region: Russian Federation –
Source: Peter the Great St. Petersburg Polytechnic University –
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Scientists from Peter the Great St. Petersburg Polytechnic University have developed a new dosage form with encapsulated antitumor compounds for use in the oral treatment of both primary and metastatic melanoma. The researchers synthesized nanoparticles from biocompatible and biodegradable polymers—gelatin (GNPs) and chitosan (ChNPs)—loaded with the therapeutic compound. Research has shown that the nanoparticles help the compound maintain its integrity while passing through the aggressive environment of the human gastrointestinal tract. This allows for maximum effectiveness in oral targeted cancer therapy. The study results were published in the International Journal of Biological Macromolecules.
According to research, melanoma is one of the most aggressive cancers with high metastatic activity. Metastases are the main cause of death in melanoma patients. Standard chemotherapy protocols typically use cytostatic and cytotoxic drugs to destroy cancer cells. However, this approach also has the side effect of destroying healthy cells. A new, modern method is targeted therapy, which destroys only tumor cells. Currently, more than 150 targeted compounds have been approved for the targeted therapy of various oncological diseases. The use of these drugs offers advantages over traditional chemotherapy, as they reduce toxicity to healthy tissue and minimize side effects. Scientists are developing both new, effective drugs and methods for improving their bioavailability.
Researchers are currently studying the efficacy of targeted small-molecule drugs, such as PARP (poly(ADP-ribose) polymerase) inhibitors, in melanoma treatment. Despite their effectiveness, their use is limited by their pharmacokinetics. The main problem with existing PARP inhibitors is their low oral bioavailability. The acidic environment, enzymes, and other biological barriers of the gastrointestinal tract degrade the drug, requiring high doses and reducing its effectiveness.
Scientists from the Institute of Biomedical Systems and Biotechnology at Peter the Great St. Petersburg Polytechnic University focused on creating an effective dosage form for PARP inhibitors that would allow the compounds to maintain their integrity in the gastrointestinal tract. The researchers synthesized nanocarriers based on biocompatible and biodegradable polymers—gelatin (GNPs) and chitosan (ChNPs). These nanoparticles encapsulated a PARP inhibitor synthesized by the study's authors, based on substituted 2-aminothiophene (2AT) derivatives.
In experiments on mice with a solid melanoma model, oral administration of the compound using the new dosage forms resulted in tumor growth suppression by 88–95% compared to the control group. In a model of metastatic melanoma with lung lesions, the nanoformulations of the drug demonstrated an 82% suppression of metastasis formation, noted Sergey Shipilovskikh, PhD in Chemistry and leading researcher at the Laboratory of Nano- and Microencapsulation of Biologically Active Substances at SPbPU.
Using bioimaging techniques (SPECT and fluorescence imaging), scientists have documented that the nanoparticles, after oral administration, effectively accumulate and remain for a long time in the gastrointestinal tract (stomach, small intestine, and colon). This confirms their ability to overcome gastrointestinal barriers and deliver the drug to its target. Studies including histological analysis of organs and blood biochemistry revealed no serious adverse effects from the new dosage forms. The drugs demonstrated a good safety profile.
"Our study demonstrates that encapsulating a PARP inhibitor in gelatin and chitosan nanoparticles increases its bioavailability and therapeutic efficacy when administered orally. This approach allows for effective treatment of not only the primary tumor but also metastases, which is critical for melanoma treatment," noted Anna Rogova, a research assistant at the Laboratory of Nano- and Microencapsulation of Biologically Active Substances at SPbPU and a postgraduate student in Biophysics.
The developed strategy opens up new prospects for the creation of effective and safe oral drugs for targeted therapy of oncological diseases.
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