Nanotechnology improves treatment of osteoarthritis in dogs

An unprecedented project in Brazil uses nanocrystals to advance veterinary medicine.

By Roseli Andrion  |  Agência FAPESP – Older dogs may limp, have difficulty getting up, or be reluctant to go for walks. These characteristics are typical of animals with arthritis and affect the quality of life of pets. Now, a drug improved by a Brazilian scientist may provide relief from these symptoms and transform the lives of millions of dogs.

Luiza de Oliveira Macedo has dedicated herself to finding a way to enhance the effectiveness of firocoxib, an anti-inflammatory drug already used to treat osteoarthritis in dogs. The drug is available in Brazil as a tablet, but it has low solubility, meaning it does not dissolve well in animals’ bodies. This hinders absorption and consequently reduces the drug’s therapeutic effect.

The challenge, then, was to improve the drug’s effectiveness. The solution came from nanotechnology. By transforming firocoxib into nanocrystals, which are very small particles almost invisible to the naked eye, the drug dissolves much more easily in the body. “In order to be absorbed and have an effect, it needs to dissolve. Nanotechnology is a resource for increasing the drug’s solubility and allowing it to combat the pain and inflammation caused by osteoarthritis,” she explains.

A conventional formula contains particles ranging from 20 to 30 micrometers (μm). However, a substance subjected to high-energy grinding can have particles reduced to 250 to 270 nanometers (nm). “The drug we obtained has 200 nm particles.” Although solutions with nanocrystals already exist for human medicines, the veterinary firocoxib developed by Macedo is pioneering in this field. “As far as we know, there’s nothing similar in the scientific literature or on the market.”

A union of willing minds

The proposal arose from Macedo’s desire to delve deeper into pharmaceutical technology. To this end, she sought out Professor Nádia Araci Bou-Chacra, her doctoral research advisor at the University of São Paulo (USP), and became involved in the project in partnership with Laboratório Duprat. The company wanted to explore the use of nanotechnology in veterinary medicine. “It was a union of willing minds. They wanted to innovate, and I wanted to learn more about this area.”

During the course of the research, Macedo developed a prototype for the new drug. Initial laboratory tests revealed the product’s characteristics. The experiment was then expanded to include testing on healthy dogs, and the results were surprising: “The concentration of the drug in the blood of these pets was twice that obtained with the conventional product. This shows that the new format is much more efficient.”

Since firocoxib is used to treat pain and inflammation, this gain in effectiveness can make a huge difference in the quality of life of sick animals. “This represents the potential to relieve the pain of these dogs much more quickly,” she explains.

Macedo has a degree in pharmacy from the Federal Rural University of Rio de Janeiro (UFRRJ) and has always focused on the human field. “When the chance to work with drugs for dogs came up, I saw an opportunity to learn something new and challenging,” she says. “There are several particularities that require specific solutions. Every detail needs to be studied specifically for dogs, from how the drug is absorbed to how it’s eliminated from the body. That fascinated me.”

This discovery comes at a time when pets are living longer and owners are taking better care of them. According to the Pet Brasil institute, there are more than 54 million dogs in the country. As pets age, diseases such as arthritis become more common, and more effective medications are needed to improve the lives of millions of families. “People have been taking better care of animals. As they live longer, these diseases can appear in the aging process,” she notes.

To the market

The prototype was synthesized in small quantities, about 7 grams at a time. The next step is to increase production to an industrial scale. “I did preliminary tests in a larger grinder and managed to produce 3 kilograms of medicine with the same characteristics,” she says. “This shows that the process has the potential to be scaled up.”

Despite the promising results, the drug still has a few steps to go before it hits the shelves. “I estimate that it’ll take three to four years to reach the market. We need to comply with several regulatory steps determined by the Ministry of Agriculture, Livestock, and Supply [MAPA],” she says. “We’ve already submitted a patent application to the National Institute of Industrial Property [INPI] to protect the innovation.”

According to Macedo, the patent was a constant concern during development. “New articles and patents involving nanocrystals are emerging all the time. During the process, there was a lot of concern that we could be overtaken by other researchers.” The patent ensures that the innovation developed in Brazil will be protected for 20 years – enough time for the company to recoup its investment and profit from the discovery.

Promotion

One of the project’s greatest assets was the support received from FAPESP’s Innovative Research in Small Businesses Program (PIPE). This was essential in building confidence in the partner company. “Since nanotechnology is new in the veterinary field, they were a little apprehensive,” she recalls.

In addition, the program encouraged the researcher to leave the laboratory and speak with veterinarians and pet owners to understand what they really needed. “FAPESP was essential. In addition to financial support, they encouraged us to talk to the market and understand what the customer was looking for,” she explains. “We had to determine what they expected from a veterinary product, and the answers were surprising. We discovered that they’re concerned not only with efficacy but also with the form of administration, taste, and even packaging.”

Macedo says she is proud to help bring science closer to the market. “Often, what we develop at the university goes unused. Seeing this project with a real chance of reaching animals is actually very rewarding,” she comments.

Versatility and possibilities

Although she does not yet know the price, Macedo estimates it will be similar to existing market prices. “The equipment used to prepare the nanocrystals isn’t very expensive,” she explains. “Even so, a product with nanotechnology has more added value.”

She points out that nanotechnology is highly versatile. “If the drug isn’t very soluble, we can try to improve it.” This discovery may therefore be useful in improving other formulas with similar absorption difficulties. “There’s a tendency to optimize drugs by reducing the dose or improving their effectiveness, for example. There’s room for growth in both human and veterinary medicine,” she says.

The project demonstrates how Brazilian science can generate innovations that directly benefit the population. “We developed it, characterized the material, and conducted toxicity and animal tests,” Macedo summarizes. All of this was done in Brazil with national resources and knowledge developed at public universities. “And the coolest thing is knowing that, in the end, it’s people – and their pets – who benefit.”