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Design of a low-cost photomodulator for in vivo photoactivation of a mGluR5 inhibitor

Ajieren, H.; Fox, A.; Biggs, E.; Albors, G.; Llebaria, A.; Irazoqui, P.

2023-10-10 pharmacology and toxicology
10.1101/2023.10.07.561310 bioRxiv
Show abstract

Severe side effects prevent the utilization of otherwise promising drugs in treatments. These side effects arise when drugs affect untargeted tissues due to poor target specificity. In photopharmacology, light controls the timing and the location of drug delivery, improving treatment specificity and pharmacokinetic control. Photopharmaceuticals have not seen widespread adoption in part because researchers do not always have access to reliable and reproducible light delivery devices at prices which fit within the larger research budget. In this work, we present a customizable photomodulator for use in both wearable and implantable devices. For experimental validation of the photomodulator, we photolyse JF-NP-26 in rats, producing raseglurant, a mGluR5 inhibitor shown to have antinociceptive effects in animal models. We show our photomodulator produces a significant reduction in pain response in the formalin model by photoreleasing raseglurant, indicating our photomodulator can successfully drive in vivo photopharmacology. We demonstrate modifications which enable the photomodulator to operate wirelessly. By documenting our photomodulator development, we hope to introduce researchers to a simple solution which significantly lowers the engineering barriers to photopharmacology research.

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