Material allows local and controlled release of medications, minimizing side effects
The side effects, often devastating, that certain drugs used in chemotherapy cause in the body are known. Intended to attack cells that spread quickly, such as cancer cells, they also destroy healthy cells. The most visible and well-known effect is hair loss, whose cells naturally renew themselves at a greater speed than other cells in the body and, therefore, are more vulnerable.
To minimize these harmful actions, nanoparticles have been created that transport drug molecules directly to diseased cells, a resource that has been extended to the healing of organs affected by different diseases. Within this perspective, the line of research coordinated by professor Cátia Cristina Capelo Ornelas Megiatto, from the Department of Organic Chemistry of the Institute of Chemistry (IQ) at Unicamp, has as its main focus the development of organic and hybrid nanomaterials for applications in nanomedicine, aiming to controlled release of drugs at specific sites. This is shown in the doctoral thesis recently presented by his advisor Tiago Branco Becher, who worked on the formulation of new injectable hydrogels and biodegradable nano-hydrogels for use in drug delivery.
Although, in the longer term, the objective of the studies guided by the professor is nanorobots, currently the materials developed by the group to obtain nanoparticles are quite diverse. Nano-hydrogels are among them, along with injectable hydrogels produced and tested for application in specific locations or for topical use. The studies also involve obtaining dendrimers, molecular compounds with tree-like structures, an arrangement that allows the addition of agents with different functions to each branch, both those aimed at attacking specific diseases such as prostate, breast and ovarian cancer. , such as those that allow you to follow the drug’s route through images.
The group also works with nanoparticles from natural polymers derived from molecules of a type of sugar, duly modified for the encapsulation of drugs. In fact, studies are being carried out with a view to obtaining nano-particles that make it possible to conduct a cocktail of antibiotics in order to make them reach more directly and powerfully the most resistant bacteria, which helps to minimize the organism's growing resistance to these bacteria. medications. All of these works involve different stages: initially, the formulation of the material suitable for the production of nano-particles with the desired properties is developed; then tests are carried out vitro with the aim of verifying the biocompatibility of the material used; finally, still invitro, Biological tests are carried out with nanoparticles functionalized by drugs in diseased cells.
Cátia Megiatto, who came to Unicamp five years ago attracted by its international prestige, graduated in chemistry from the University of Madeira, Portugal, studied for a doctorate at the Université de Bordeaux 1, France, and completed five years of post-doctorate at three universities American universities: Arizona State University, University of California Berkeley and New York University.
A specific study
In relation to the work of her advisor Tiago Becher, the IQ professor distinguishes two parts. The first aimed to develop a new type of hybrid hydrogel – consisting of a polymer, silica nanodiscs and around 95% water – aiming for its injectable application for controlled release of drugs in specific locations, for example, directly at the site of a recently removed tumor to eliminate any remaining cancer cells. The hydrogels obtained turned out to be biocompatible, biodegradable and robust, that is, their particles remain intact and self-recoverable – although the gel turns into a liquid during injection, once the syringe pressure stops, it returns to gel; and do not undergo swelling, volume expansion due to the absorption of water, which would lead to the explosion of the particles. All of these properties are fundamental in injectable hydrogels.
The results obtained led to a collaboration with the research group led by professor François Berthod, from the University of Laval, in Quebec (Canada), in which hydrogels are being tested as possible candidates for accelerating skin healing. Another cooperation was established with the research group coordinated by professor Marcelo Bispo, from the Institute of Biology (IB) at Unicamp, which tests the hydrogel in vivo in mice, aiming at the recovery of the sciatic nerve. In both studies, preliminary results show high biocompatibility of the material in vivo and efficiency in the controlled release of drugs.
In the second part of the work, the best formulations found to obtain macroscale hydrogels were then also tested on the nanoscale, with the particles obtained through a nanoemulsion process, resulting in nanodroplets with a diameter between 100 and 200 nm (one nanometer corresponds to to 10-7 cm). In this form, the material is injected into the bloodstream, which takes it to the desired location. Tiago Becher managed to add up to three drugs to the nano-hydrogel simultaneously. To combat cancer cells in general, the addition of this cocktail of drugs did not prove to be more effective than the use of a single drug. However, for breast cancer, the efficiency of the cocktail developed was ten times greater than the drug currently used, a very important result for combating more advanced cases of the disease, in which the cells are more resistant.
The professor explains that when cancer cells grow, they do so in such an uncontrolled way that pores appear between them that are larger than those found in healthy tissues, where they are distributed in an organized and well-defined way. The nanoparticles, although small, are still large enough to penetrate the pores involved by benign cells, but small enough to reach the pores resulting from the disordered growth of cancer cells, where the drugs are then progressively released. This mechanism gives a general idea of its use in nanomedicine.
Cátia Megiatto emphasizes that the hydrogel can be functionalized according to different medical needs, such as in cases of post-surgical cancer therapy, in which it is placed at the tumor extraction site; injection to recover the sciatic nerve; of topical application for skin regeneration. Nanohydrogels also offer the ability to carry several drugs simultaneously, increasing the probability of attacking more advanced stages of cancer cells. Studies have demonstrated a significant increase in the efficiency of anticancer drugs when incorporated into the structure of nanohydrogels, which highlights the great potential of these new materials.