New drug delivery system developed for prolonged pain relief
The treatment of musculoskeletal pain is a key challenge due to the short duration of the anaesthetic effect produced by existing clinical treatments, in addition to their potential side effects. In this line, researchers from the CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), from the Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, from the Instituto de Investigación Sanitaria de Aragón (IIS Aragón), in collaboration with researchers from the Faculty of Veterinary Medicine of the University of Zaragoza, have developed nanogels loaded with nanocrystals of bupivacaine (anaesthetic commonly used in epidural anaesthesia and postoperative pain control) obtaining a high drug content for a prolonged duration of local anaesthesia.
These nanogels are an alternative to the most commonly prescribed analgesics (antipyretics, steroids and opioids), which often have adverse effects such as nausea, vomiting, dizziness and physical dependence, among others. They are made of a biocompatible polymer derived from polyethylene glycol (PEG) that has thermosensitive properties, so that they would be injected at room temperature and when they reach body temperature after administration they undergo a change in their structure, resulting in a reduction of their volume and transforming into a hydrophobic structure, thus controlling the release of the drug encapsulated inside.
According to Manuel Arruebo, a researcher at the Instituto de Nanociencia y Materiales de Aragón, INMA and CIBER-BBN, “we have validated this new way of dispensing the local anaesthetic both in cell cultures and in animal experiments, demonstrating that it doubles the duration of sciatic nerve blockade compared to the same dose of free anaesthetic”.
The prolonged duration of anaesthetic action can be explained by the regional immobilisation of the nanogels at the injection site around the sciatic nerve due to their hydrophobic character, preventing diffusion of the drug particles and their rapid elimination while interacting efficiently with the tissues thanks to their temperature-induced conformational change. Studies have shown that this delivery system has low toxicity and does not lead to an inflammatory response due to the slow release of the drug and the high biocompatibility of the polymer used.
A promising strategy with low toxicity
Nanocrystal encapsulation of drugs is a promising strategy, reducing the total amount of drug needed to produce pain relief with the consequent benefits of reduced toxicity.
For their part, researchers Teresa Alejo and Victor Sebastian INMA researchers and CIBER-BBN researchers say that “through these systems are seeking to obtain an effective vehicle capable of prolonging the anesthetic effect in place of action, avoiding as far as possible the side effects. In this way they could be used to avoid systemic administration, reduce high concentrations in the blood and reduce the undesirable side effects of some conventional treatments, as they make it possible to control the release of the drug within the desired therapeutic range, avoiding the consequences of an excess of drug and the negative effects that this entails”.
50% of short absences from work and 60% of permanent absences from work
In addition, this technique is designed for the patient’s comfort and convenience, as a single dosage would achieve a prolonged therapeutic effect. In Europe, with more than 500 million sick days per year, musculoskeletal pain causes almost 50% of all absences from work lasting at least three days and 60% of permanent absences from work. Consequently, pain has a huge impact on work productivity. Some data indicate that the annual cost of pain is higher than the cost of heart disease, cancer and diabetes.
Therefore, the development of an effective injectable local anaesthetic with a prolonged duration of action may improve the quality of life of patients affected by these diseases.
Reference article:
“Nanogels with high loading of anesthetic nanocrystals for extended duration of sciatic nerve block”. ACS Appl. Mater. Interfaces 2021, 13, 15, 17220-17235. Teresa Alejo, Laura Usón, Guillermo Landa, Martín Prieto, Cristina Yus Argón, Sara García-Salinas, Ricardo de Miguel, Ana Rodríguez-Largo, Silvia Irusta, Víctor Sebastián, Gracia Mendoza and Manuel Arruebo. https://pubmed.ncbi.nlm.nih.gov/33821601/.
Foto:
Víctor Sebastián (INMA), Laura Usón (INMA), Silvia Irusta (INMA), Teresa Alejo (INMA), Manuel Arruebo (INMA), Cristina Yus (INMA).
11/06/2021
