Researchers at the Vall d'Hebron Research Institute (VHIR) have developed a new injectable hydrogel made exclusively from natural polymers that enables local and sustained chemotherapy delivery. The system has demonstrated antitumor activity in models of ovarian cancer and glioblastoma, with high biocompatibility and the potential to reduce the systemic toxicity associated with conventional treatments. The results have been published in the journal Carbohydrate Polymer Technologies and Applications.

Systemic chemotherapy treatments have significant limitations, including low specificity, adverse effects, and the difficulty of maintaining high drug concentrations at the tumor site. To overcome these challenges, researchers from the Clinical Biochemistry, Drug Delivery and Therapy Group at VHIR designed a soft, injectable hydrogel composed of cellulose and chitosan, two biodegradable natural biopolymers, capable of acting as a local chemotherapy depot.

"Our goal was to develop a completely natural and sustainable platform capable of delivering treatment directly to the tumor and maintaining drug release over days or weeks, thereby minimizing side effects on healthy tissues," explains Diana Fernandes, researcher in the Clinical Biochemistry, Drug Delivery and Therapy Group at VHIR and principal investigator of the study.

To incorporate docetaxel, a highly potent but poorly soluble drug, the researchers encapsulated it in polymeric micelles approximately 72 nanometres in diameter, which were subsequently integrated into the hydrogel. Thanks to this dual strategy, the system was able to release approximately 70% of the drug over a period of 14 days while maintaining its structure for more than three weeks under physiological conditions.

From computational modelling to biological validation

Before manufacturing the hydrogel, the researchers used molecular simulations and computational modelling tools to predict the interactions among the different components of the system and optimize its formulation.

"The use of in silico models has enabled us to understand how the polymer network is organized and how the drug is incorporated, helping us design a stable and efficient formulation," says Magalí Sureda, researcher in the Clinical Biochemistry, Drug Delivery and Therapy Group at VHIR.

Rheological studies showed that the hydrogel exhibits thixotropic behaviour, meaning that it becomes more fluid during injection and recovers its structure once administered, forming a local depot at the application site. In addition, studies in mice confirmed its injectability and its ability to remain localized at the administration site*.

Efficacy in ovarian cancer and glioblastoma models

The researchers evaluated the biocompatibility of the system in healthy fibroblasts and observed that it did not induce toxicity or oxidative stress. They then assessed its antitumor activity in ovarian cancer and glioblastoma cell lines, as well as in three-dimensional glioblastoma models.

The results demonstrated that the micelles released by the hydrogel are capable of penetrating deeply into tumor spheroids and exerting sustained cytotoxic activity. Although the effect is more gradual than that of the free drug, this strategy allows prolonged exposure to the treatment while reducing the concentration peaks associated with increased toxicity.

“Tumors such as glioblastoma and ovarian cancer are particularly difficult to treat because they present barriers that limit drug delivery. A local and prolonged drug delivery system could improve treatment efficacy while reducing adverse effects”, highlights Diana Fernandes, beneficiary of the Junior Leader postdoctoral scholarship from the ”la Caixa” Foundation.

A versatile platform for new local therapies

Although the results are still limited to preclinical studies, the researchers believe that this technology could be adapted to other types of solid tumors and to different drugs.

"We believe this platform offers a promising alternative for developing more precise and less invasive therapies. Furthermore, the fact that it is composed exclusively of natural biomaterials and does not require chemical cross-linking agents facilitates its future translation into clinical applications," concludes Magalí Sureda.

The research was carried out with the participation of CIBER-BBN, the Functional Validation and Preclinical Research Platform (U20) of NANBIOSIS, the University of Barcelona, the Universitat Autònoma de Barcelona, and several international research centres. The study combines computational modelling, nanotechnology, and advanced biological validation to develop new strategies for the local treatment of cancer.

*Institutional Statement on the Use of Research Animals