Researchers at Jagiellonian University have developed a new way of administering a drug used in brain cancer therapy. The approach could potentially increase treatment effectiveness and improve patients’ quality of life. The solution enables the drug to be delivered in two ways: directly into the brain during tumor resection surgery, and as an aerosol through the patient’s nasal cavity.
The method is based on local delivery of temozolomide (TMZ)—currently the most commonly used chemotherapeutic agent for malignant brain glioma—using innovative biopolymer platforms. Thanks to their properties, these carriers meet key requirements for oncological therapy:
- They release the drug gradually, over an extended period, and only where it is needed—meaning the highly toxic therapeutic agent can act with maximum effectiveness while minimizing side effects.
- They help bypass the blood–brain barrier (the biochemical barrier separating the bloodstream from nervous tissue), which is one of the major challenges in current chemotherapy for the central nervous system.
- Their chemical composition is fully biocompatible with the patient’s body, and the carrier components have beneficial properties that may additionally support therapy.
- After administration, the carrier does not negatively affect healthy tissue cells.
The newly developed TMZ carriers are the result of several years of interdisciplinary collaboration at Jagiellonian University, conducted under the medical supervision of Dr. Ewelina Grzywna, MD, PhD, from the Department of Neurosurgery and Neurotraumatology at the University Hospital in Kraków.
Bypassing the blood–brain barrier
The driving force behind the research was the need to develop a solution that could become a supportive tool in glioma therapy. Standard chemotherapy with temozolomide can cause serious side effects, significantly reducing patients’ comfort. This is because the highly toxic drug is typically administered orally (or less often intravenously), and therefore acts systemically—on the entire body, not only on cancer cells.
“We wanted to develop a way to administer TMZ directly to the brain affected by the tumor, so as to bypass systemic circulation. If we succeed, TMZ will act with maximum effectiveness while the side effects of its use will be minimal. For several years we have been working on universal biopolymer systems which in the future could be widely used by the medical community as drug carriers. At this stage, I can say we have promising results,” says Dr. Ewelina Grzywna from the University Hospital in Kraków.
A drug delivered through the nose
Importantly, the formulations developed at Jagiellonian University make it possible to administer TMZ not only during tumor removal surgery (directly, as a lining substance placed in the cavity left after the tumor is removed), but also through the nasal cavity—in the form of an aerosol delivered with an atomizer.
“Intranasal administration of TMZ is minimally invasive. In this case, the drug, which is slowly released from the gel preparation, reaches the brain via nerve endings in the nasal cavity—specifically the olfactory and trigeminal nerves—without entering the patient’s bloodstream in significant amounts. The carrier we developed has mucoadhesive properties, which means it migrates more slowly from the nose to the throat with mucus and adheres to the mucosa, allowing it to act longer,” explains one of the technology’s co-creators, Dr. habil. Joanna Lewandowska-Łańcucka, Professor at JU, from the Faculty of Chemistry at Jagiellonian University.
“Applying TMZ directly to the cavity left after tumor removal, as well as via the intranasal route, may change current methods of treating brain tumors. There is not yet a single formulation of this drug approved for medical use anywhere in the world. At the same time, we emphasize that this novel method does not mean an attempt to eliminate traditional systemic chemotherapy. It may, however, serve as a complementary component of therapy—an option for patients who do not qualify for standard systemic treatment,” adds co-creator Aleksandra Krajcer, MSc, from the Doctoral School of Exact and Natural Sciences at Jagiellonian University.
Advanced research work
So far, the team has conducted a series of studies necessary to bring the technology into clinical practice. In in vitro tests, the researchers demonstrated that the new carrier releases the drug gradually and in a controlled manner, allowing the therapeutic agent to act for a longer period—thereby increasing its effectiveness. In addition, the formulation designed for intraoperative TMZ delivery has appropriately low swelling parameters, which is crucial for local application: the preparation does not compress tissue (the so-called mass effect) or cause local increases in pressure.
“Our studies showed that TMZ gradually released from the carrier inhibits glioma cancer cell division by 90% under laboratory conditions. Moreover, our composition successfully passed biocompatibility testing in in vitro/ex vivo settings. We know the drug carrier is not harmful to healthy cells,” says co-creator Dr. Alicja Hinz from the Faculty of Biochemistry, Biophysics and Biotechnology at Jagiellonian University.
What is the new TMZ carrier?
The technology is a specialized hydrogel obtained by combining methacrylated biopolymers: gelatin, chitosan, and hyaluronic acid. They are crosslinked using UV light in the presence of a photoinitiator. The resulting system can contain temozolomide (TMZ) embedded in its structure—both in a free form and in a modified form.
After administration, the preparation undergoes slow biodegradation, and the drug is released gradually. This offers significant benefits compared to systemic administration of higher TMZ doses. The toxic drug acts primarily at the site of administration rather than systemically, and its duration of action is extended.
It is worth noting that the components used to build the carriers—chitosan and hyaluronic acid—have beneficial effects on the human body. Chitosan exhibits anti-inflammatory, antibacterial, and anti-hemorrhagic activity, while hyaluronic acid, as a gel-like extracellular matrix, supports wound healing and also has anti-inflammatory effects.
The path to commercialization
The biopolymer TMZ carriers developed at Jagiellonian University, along with the methods of administration, are the subject of several patent applications. The Jagiellonian University Technology Transfer Center (CITTRU), which is responsible for commercializing the solutions, is currently establishing relationships with biomedical and pharmaceutical partners with whom further research can be carried out.
“We have reached a stage of technology development at which it is necessary to cooperate with specialized entities in order to conduct clinical trials. These trials will allow us to ultimately confirm that the developed methods of administering TMZ are effective and safe for patients. Clinical trial phases require substantial funding and are time-consuming; nevertheless, I trust that the technologies developed by our scientific team will reach the market in the future,” said Dr. Eng. Gabriela Konopka-Cupiał, Director of CITTRU at Jagiellonian University.
Co-creators of the presented technologies also include Dr. habil. Monika Bzowska, Professor at JU, and Sylwia Stankiewicz, MSc, from the Faculty of Biochemistry, Biophysics and Biotechnology at JU, as well as Adrian Grzonka from the Faculty of Chemistry at JU. The research was funded by the National Science Centre (NCN) under the OPUS 21 project titled: “In search of solutions to limitations in the use of temozolomide (TMZ) in the therapy of brain glioma.”
Jagiellonian University in brief
Jagiellonian University (JU) is the oldest university in Poland and one of the oldest in Europe, founded in 1364 by King Casimir III the Great. For more than 650 years, it has educated successive generations of students, researchers, and public leaders. Based in Kraków, Alma Mater Jagiellonica combines centuries-old academic tradition with a modern approach to science, teaching, and innovation.
JU comprises 16 faculties and offers programs in more than 80 fields, spanning the humanities, social sciences, natural sciences, medicine, and engineering. The university ranks among the top institutions in national and international rankings, and its alumni include Nicolaus Copernicus, Pope John Paul II, and Wisława Szymborska.
Jagiellonian University is also a major center of research and innovation. Through CITTRU and its special-purpose companies, it supports the commercialization of research results and cooperation with business. It also carries out numerous international projects in collaboration with leading universities worldwide.
Source: CEO.com.pl (article about JU’s new method of delivering temozolomide in glioma treatment).
