Light-activated drugs are compounds that are activated when they are irradiated by a beam of light – directed by an optical fibre – and thus generate a therapeutic effect in a controlled and local way on the target tissues. Now, a scientific team has promoted a new advance in the field of photopharmacology with the design of the first wireless device capable of activating a light-activated drug by remote control and making it have a therapeutic effect on specific organs. The new device has demonstrated its effectiveness in the treatment of pain in a study with a photosensitive molecule derived from morphine, one of the most widely used opioids due to its great analgesic capacity.
The work, carried out in animal models, opens up new perspectives for the design of safer, more effective and customizable analgesic treatments – especially in the context of chronic pain – and without causing the adverse effects derived from the use of opioids (addiction, dependence…). This innovation in pharmacology is announced in an article published in the journal Biosensors and Bioelectronics, whose main authors are Dr. Francisco Ciruela, leader of the Neuropharmacology and pain research group at IDIBELL, professor at the Faculty of Medicine and Health Sciences of the UB and member of the Institute of Neurosciences (UBNeuro), and the experts John Rogers, from Northwestern University (United States), Amadeu Llebaria, from the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC) and Jordi Hernando, from the Autonomous University of Barcelona (UAB).
Photopharmacology: The Power of Light
Light-activated drugs are chemical compounds that are inactive until they are activated with light of a specific wavelength. Thanks to this, they can act with more spatial and temporal precision, and without generating significant adverse effects on the body.
In the study, the team evaluated the effects of new wireless technology on pain management by using photolabile morphine (pc-Mor), which promotes the release of active morphine in pain-affected organs and tissues without causing side effects.
“Photolabile morphine is a molecule chemically modified to temporarily inactivate its analgesic function. This inactivation is achieved by the addition of a coumarin group that covalently binds to morphine via a bond. This binding blocks the morphine domain that is responsible for its interaction with opioid receptors,” explains Francisco Ciruela. “When the target tissue is irradiated with light of 405 nanometers wavelength, the bond is broken and the active morphine is released at the point where it is meant to act. This allows for precise pharmacological action in space and time, that is, it acts only where and when it is needed,” explains the expert.
The same effect as morphine given on a regular basis
According to the study’s conclusions, the analgesic effect of morphine released locally into the bone marrow with the photodevice was comparable to that of morphine administered systemically.
“However, the notable difference was the absence of the characteristic adverse effects of opioids, such as tolerance to the analgesic effect, rubbing, dependence or addiction,” Dr. Ciruela emphasizes. “Overcoming the potential dependence and side effects associated with opioids has been one of the main motivations for the new photopharmacological approach.”
To carry out the research, the team implanted in animal models a millimetre-sized device that incorporates a micro-LED as a light source to activate photolabile morphine in the spinal cord and induce analgesic effects. This configuration allows the micro-LED to be activated in a programmable and modulable way to induce the local photorelease of morphine only in the irradiated region.
The device integrates a mini radio frequency antenna that receives energy wirelessly – without wires or wiring – using NFC (near field communication) technology to turn on the micro-LED. Once implanted in animal models, the device facilitates free movement through the environment and eliminates physical barriers that could alter the therapeutic efficacy of the photopharmaceutical. The system also allows the intensity and frequency of the irradiated light to be regulated to improve the control of light doses and the pharmacological effect according to therapeutic needs.
New frontiers of wireless photopharmacology
Beyond pain treatment, the new wireless photopharmacology protocol could also be applied in various pathologies. In particular, in the personalised treatment of chronic diseases that require very precise pharmacological action or that involve risks associated with systemic adverse effects.
“In the case of epilepsy, the local release of anti-seizure drugs in specific regions of the brain could allow seizure control without affecting the rest of the central nervous system, thus avoiding sedation and other general side effects,” says Dr. Ciruela. “In neurodegenerative diseases, such as Parkinson’s, local photo-release of dopaminergic drugs or other modulators could be used to improve motor symptoms in a focal and safe manner. In psychiatric disorders, such as schizophrenia, light activation of antipsychotics in specific brain areas could increase therapeutic efficacy, reduce adverse effects, and improve patient adherence to treatment.”
In the fight against cancer, the photorelease of chemotherapy drugs directly into the tumour environment could be a strategy that would ensure a high local concentration of the drug and lower systemic toxicity.
In the future, clinical research in photopharmacology will address challenges such as evaluating the bioavailability, chemical stability, and safety of photolysis byproducts. From the technological side, the development and validation of implantable devices poses various challenges, such as biocompatibility, durability, miniaturization, energy management and their functional integration into the human body. “From a regulatory perspective, this technology will also require specific regulation for combination products, as it integrates a drug with a medical device, which complicates the process of approval and clinical supervision,” concludes the expert.
About IDIBELL
The Bellvitge Biomedical Research Institute (IDIBELL) is a research centre created in 2004 and specialising in cancer, neuroscience, translational medicine and regenerative medicine. It has a team of more than 1,500 professionals who, from 73 research groups, publish more than 1,400 scientific articles a year. IDIBELL is owned by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.
IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centres accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the HR Excellence in Research program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Centre of the AECC Scientific Foundation (FCAECC).
About the University of Barcelona
Founded in 1450, the University of Barcelona is the main public university in Catalonia and one of the most prestigious institutions of higher education in Spain. The UB is the only university in Spain that is part of the League of European Research Universities (LERU), an association that brings together the 23 most important university research centres on the continent. According to the Center for World University Rankings (CWUR), the UB is among the top 150 universities in the world and, according to The Times Higher Education, the UB is one of the top 25 in the world with more than 400 years of history.
The University of Barcelona has a wide range of training courses, covering 73 bachelor’s degrees, 158 official university master’s degrees and 48 doctoral programmes (2020-2021 academic year). It has more than 41,000 undergraduate students and 19,000 master’s, postgraduate and doctoral students. 15% of the students are international, of 137 different nationalities.
As a public institution, the UB, focused on academic excellence, is committed to continuing to provide the next generations of citizens – professionals, researchers, entrepreneurs, leaders – with the ability to work at the highest level anywhere in the world.