A team of researchers from Coimbra invented a non-invasive and voluntary procedure for taking drugs, thinking about the well-being of the rodents used in the experiments. The innovation, which received a European award and is awaiting a patent, is proving to be promising, inside and outside the laboratory.

HaPILLness. The name says it all: pill and happiness. It is an innovative approach, started four years ago, and aimed at rodents used in pre-clinical laboratory tests, and which may represent the end of a painful process for guinea pigs: gavage. Instead of being administered the precise dosage of the compound to be tested by means of a gastric tube, the animals started to have, in their racks, small colored gums for this purpose.

Semi-solid matrices: the alternative to invasive methods of giving drugs to guinea pigs, saving them suffering and with promising applications

“The versatile semi-solid matrices incorporate bioactive compounds and allow for oral dosing and voluntary ingestion, safely and effectively”, clarifies the researcher in charge, Sofia Viana, who developed the invention with scientist Flávio Reis.

The project “HaPILLness” – Refining oral dosage in experimental animals” results from a partnership between the Faculty of Medicine of the University and the Polytechnic Institute of Coimbra and meets the European Directive on the Use of Guinea Pigs for Scientific Purposes.

The Coimbra team focused on refining the procedure in order to reduce as much as possible the limitations faced by researchers and guinea pigs: “Until now, the animal was restrained and subjected to a very invasive and stress-generating procedure, altering organic variables (heartbeats, stress hormones in circulation, etc) that compromised the results”, says the professor at the Polytechnic Institute of Coimbra.

Animal welfare in the administration of drugs to laboratory guinea pigs
To use the new non-invasive resource, it was necessary to adapt the characteristics of the matrices to the preferences of the animals, which mainly respond to the senses of touch and smell: “In training, we introduce the matrices, which work as treats, and without any active ingredient, until that they learn to ingest them completely.” This stage is reached in a period of three to five days. “Then we incorporate the drugs into the matrices and administer them.”

So far, more than 500 guinea pigs (in rats and mice), healthy and sick, have been dosed with the aim of evaluating the degree of effectiveness of various drugs – metformin, sitagliptin (antidiabetics), pravastatin (for cholesterol), fluoxetine (antidepressant ), prednisolone (anti-inflammatory) are some examples – and natural extracts (pre and probiotics).

Among the diseases studied, renal, metabolic and central nervous system diseases stand out. “We are currently testing the oral dosage of drugs in various disease models to see if there is any in which this methodology is not feasible”, she adds.

Two years ago, the innovation was awarded by the European Partnership for Alternative Approaches to Animal Testing (EPAA), a consortium that includes the European Union and stakeholders from the pharmaceutical, chemical, food and biotechnology industries and which aims to encourage the implementation of the 3Rs (Replacement, Reduction, Refinement) in laboratory experimentation.

This milestone represented a turning point and the opening of new horizons: “We started to be contacted by several companies and academies that showed interest in using our matrices.”

Now, the team has a partnership with BIOCANT – Parque Tecnológico de Cantanhede – and has received a grant from the Portuguese Society of Neurology to study the administration of drugs for multiple sclerosis.

The researchers also have funding from INOVC+ (Intelligent Innovation Ecosystem of the Central Region), and are interested in “proving the benefits of matrices in the immune system of guinea pigs, which is compromised by the gavage method, which induces stress.”

With the goal of combining science and animal welfare and transferring technology to society, Sofia Viana adds: “We hope to see this method patented by the end of the year and we want to make a product that is marketable.”

In the near future, this innovation may have other applications outside the laboratory, that is, in domestic animals such as dogs or cats, alleviating the dilemma of dosing oral medications.