The method allows the drug to be delivered either directly to the tumor site during glioma resection surgery or intranasally through the nasal cavity.

The TMZ carriers were developed over several years by an interdisciplinary team of scientists at Jagiellonian University under the medical supervision of Ewelina Grzywna from the Department of Neurosurgery and Neurotraumatology at the University Hospital in Kraków. According to the university, the method has the potential to increase therapeutic effectiveness and improve patients’ quality of life.

Currently, temozolomide, the most commonly used chemotherapy drug for malignant glioma, is administered orally or intravenously. This approach exposes the entire body to the highly toxic drug, often causing significant side effects. The researchers aimed to bypass the blood-brain barrier and deliver TMZ locally, minimizing systemic exposure.

“We wanted to develop a method for administering TMZ directly to the brain affected by cancer, bypassing the patient's systemic circulation. If this condition can be met, TMZ will be maximally effective and its side effects minimal. For several years, we have been working on universal biopolymer systems that could be widely used by the medical community as drug carriers in the future. At this stage of research, I can say that we have promising results,” Grzywna said.

The new method uses hydrogels made from methacrylated biopolymers — gelatin, chitosan, and hyaluronic acid — cross-linked with UV light in the presence of a photoinitiator. These hydrogels can incorporate TMZ in both free and modified forms, releasing the drug gradually over an extended period and directly where it is needed. Their chemical composition is biocompatible and does not damage healthy tissue, while the carriers themselves may have beneficial properties that support therapy.

The system allows two delivery options. TMZ can be applied directly to the tumor bed during surgery, lining the cavity left by the removed tumor, or administered intranasally using an atomizer.

“The intranasal method of administering TMZ is minimally invasive. In this case, the drug, slowly released from the gel formulation, reaches the brain through the nerve endings of the olfactory and trigeminal nerves located in the nasal cavity, without significantly penetrating the patient's bloodstream. The carrier we developed has mucoadhesive properties, meaning it migrates more slowly from the nose to the throat along with the mucus and adheres to the mucosa, allowing it to act longer,” said co-inventor Joanna Lewandowska-Łańcucka.

According to the researchers, combining intranasal delivery with direct tumor-bed administration could transform brain tumor treatment, as no approved TMZ formulation exists for these delivery methods worldwide.

“However, it can be a complementary therapy, a solution for those who are not eligible for standard whole-body treatment,” said Aleksandra Krajcer, co-inventor of the technology.

The research team has conducted a series of studies necessary for introducing the technology into clinical practice. The biopolymer carriers and delivery methods are the subject of multiple patent applications. Jagiellonian University Centre for Technology Transfer CITTRU is managing commercialization and establishing partnerships with biomedical and pharmaceutical companies to continue development.

The research was funded by the Polish National Science Centre as part of the OPUS 21 project. (PAP)

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