Bone implants that support and release chemotherapeutical agents in ciclodextrin nanocapsule

For the localized treatment of tumors

Bone implants with the ability to carry chemotherapeutical drugs in conception in CICECO

Chemotherapy, followed by the surgical removal of the affected tissue is the treatment usually adapted to bone tumors. An implant which can fill the areas of subtraction, while releasing chemotherapeutical agents locally, in a controlled manner, during the treatment period, is the aim of a research led by the Research Centre in Ceramic Material and Composites (CICECO/UA). In these experiences, specialists are using potential "anti-tumor" drugs coated by nanocapsules.

The osteosarcoma is the most common malignant primary bone tumor. Its major incidence is in children and youngsters and usually involves the amputation of arms and legs. The treatment for this type of tumor implies chemotherapy, followed by the surgical removal of the affected tissue with a safety area, in order to avoid the tumor's reappearance. This area is then filled with a bone or synthetic biomaterial implant.

Considering how important it is to avoid repeating new chemo or radiotherapy treatments in these cases when neutralizing possible residual focus, 11 researchers from the Universities of Aveiro and Coimbra intend to develop an implant which can contain chemotherapeutical agents of specific ranges of action, and also release these components in a controlled manner for a specific and adequate period of time.

"The bone implants we are studying will serve as a support and releasing agent of capsulated drugs in a ciclodextrin nanocapsule. We are currently experimenting with an active molecule with anti-cancer properties specifically directed to osteosarcomas. Nevertheless, it is intended to broaden its application to other types of cancer".

For this person, and as explained by Prof. Rui Correia, project coordinator, there is the need to proceed with the study of its mechanic and biological characteristics. "When we develop projects for these purposes, we must bear in mind their mechanic resistance, as well as other characteristics which must be taken in consideration when performing its implant in the bone. In this specific case, we are working with porous supports that contain a silica gel, manipulated to function both as a nanocapsule deposit and releaser. Its physical form will vary according to the bone area to fill.

The gel matrix will receive the anti-tumor compost (cisplatin and metallic composts), capsulated at a molecular level with ciclodextrin, coloured gello capsules which are nothing more and nothing less that sugar rings.

Prof. Ana Gil explains this innovative technique:

"A subgroup within our team, lead by researcher Susana Braga, is by the one hand, developing new metallic composts with a therapeutic potential and, by the other hand, promoting its capsulation in ciclodextrins. The use of the ciclodextrin on the coating of the medicinal molecule increases the efficiency of the drug and reduces the necessary amount. To work at a nanometric scale allows us to improve the properties, both concerning its solubility and its range of activity, allowing us to make it more specific".

The nanocapsule protects the therapeutic agent from the contact with proteins which are irrelevant to the treatment and makes its located application simpler. The use of ciclodextrins as nanocapsules should protect the organism from the expected high toxicity of the new agents to the healthy cells.

This project, financed by the foundation for the Science and Technology, also presents an innovative aspect in what concerns the study of the metabolic effects of the new compounds (capsulated or not) on the human osteosarcoma cells, as explained by the researcher: "It is important to know the response of the cancer cells to the drugs, in order to be able to adjust and adapt the drug's nature and dosage, for an effective treatment. These studies use the spectroscopy of the RMN- Magnetic Nuclear Resonance in the characterization of the cells' metabolic profile and the application of adequate statistic treatments, which help identifying specific metabolic changes and their relation with the patterns of cellular death".

With the drug in nanocapsules, there will be two types of implants to choose from: permanent titanium and biodegradable (for regenerative purposes) implants. The differences between these two are clarified by Prof. Rui Correia: "The porous supports which will allow the introduction of a chemic component in the organism are conceived from two types of biomaterials: a bio-stable one (non-degradable and biocompatible) and a polymeric, with biodegradable characteristics. The first one will be used in cases where there is a lack of ability to regenerate the bone tissue and the second in situations where there is the probability of a full natural recovery of the bone. In this last case the implant will be absorbed and progressively replaced by the natural bone".

Besides the microstructural analysis, the researchers are proceeding with mechanic, physics and chemistry and in vitro rehearsals. There will also be performed metabolomics essays with cellular cultures which are subjected to the therapeutic agents, either molecularly encapsulated or not.