Photoactivable drugs are activated when irradiated by a beam of light — via an optical fibre — thus generating a controlled and local therapeutic effect on target tissues. Now, a scientific team has pioneered a new breakthrough in the field of photopharmacology with the design of the first wireless capable of remotely activating a phtoactivable drug and causing it to have therapeutic effects on specific organs.
This new device has demonstrated its efficacy in the treatment of pain in a study with a photosensitive molecule derived from morphine, one of the most widely used opioids because of its great analgesic capacity.
The study, carried out on animal models, opens up new perspectives for the design of safer, more effective and customizable analgesic treatments — especially in the context of chronic pain — without causing the adverse effects derived from the use of opioids (addiction, dependence, etc.).
This innovation in pharmacology is now announced in an article published in the journal Biosensors and Bioelectronics, with Francisco Ciruela as lead author, professor at the Faculty of Medicine and Health Sciences of the University of Barcelona and member of the Institute of Neurosciences (UBneuro) and the Bellvitge Biomedical Research Institute (IDIBELL), and experts John Rogers, from Northwestern University (United States), Amadeu Llebaria, from the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), and Jordi Hernando, from Universitat Autònoma de Barcelona (UAB).
Photopharmacology: the power of light
Photoactivable drugs are chemical compounds that are inactive until activated by light of a specific wavelength. They can act with greater spatial and temporal precision, and without generating significant adverse effects in the body.
In the study, the team evaluated the effects of the wireless technology in the treatment of pain using photo-caged morphine (pc-Mor), which promotes the release of active morphine in organs and tissues affected by pain, without causing side effects.
“Photo-caged 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 photosensitive bond. This bond blocks the domain of morphine that is responsible for its interaction with opioid receptors”, explains Francisco Ciruela.
“When the target tissue is irradiated with 405 nanometre wavelength light, the photosensitive bond is broken and the active morphine is released at the point where it should act. This allows a precise pharmacological action in space and time, i.e. it acts only where and when it is needed”, the expert explains.
Same effect as morphine administered in the usual way
According to the findings, the analgesic effect of morphine released locally in the medulla with the photodevice is comparable to that of systemically administered morphine.
“However, the outstanding difference was the absence of the typical adverse effects of opioids, such as tolerance to the analgesic effect, constipation, dependence and addiction”, the expert stresses. “Overcoming the potential dependence and side effects associated with opioids was one of the main motivations”.
To conduct the research, the team implanted animal models with a small, millimetre-sized device incorporating a microled as a light source to activate photolabile morphine in the spinal cord and induce analgesic effects. This configuration allows the microled to be activated in a programmable and modulable way to induce local photoactivation of morphine only in the irradiated region.
The device integrates a mini radiofrequency antenna that receives power, wirelessly or wired, via NFC technology to turn the microled on. Once implanted in animal models, the device facilitates free movement in the environment by removing physical barriers that could alter the therapeutic efficacy of the photoactivable drug. The system also allows the intensity and frequency of the irradiated light to be regulated to improve control of light doses and pharmacological effect according to therapeutic needs.
New frontiers in wireless photopharmacology
Apart from pain treatment, the new wireless photopharmacology protocol, based on the local and controlled release of light-activated drugs, could also be applied to various pathologies. In particular, in the personalized treatment of chronic diseases that require very precise pharmacological action or involve risks associated with systemic adverse effects.
“In the case of epilepsy, local release of anticonvulsant 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 Ciruela. “In neurodegenerative diseases, such as Parkinson’s, local photoactivation of dopaminergic or other modulation drugs could be used to improve motor symptoms in a focal and safe manner. In psychiatric disorders such as schizophrenia, light activation of antipsychotic drugs in specific brain areas could increase therapeutic efficacy, reduce adverse effects and improve patient adherence to treatment”.
In the fight against cancer, photoactivation of chemotherapeutics directly into the tumour environment could be a strategy to ensure high local drug concentration and lower systemic toxicity.
In the future, clinical research in photopharmacology will face challenges such as assessing the bioavailability, chemical stability and safety of photolysis-derived products. On the technological side, the development and validation of implantable devices poses several challenges, such as biocompatibility, durability, miniaturization, energy management and 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 approval process and clinical supervision”, the expert concludes.