Descripción del proyecto
Implantes de liberación de medicamentos controlados por luz azul
La incapacidad de utilizar la luz azul ultravioleta como una señal para la administración de medicamentos a demanda activada por la luz se debe a una barrera fisiológica formidable. Esto convierte la luz roja en la única alternativa. Sin embargo, la luz roja posee intrínsecamente menos energía y un valor limitado en las reacciones fotoquímicas, porque la fotorruptura de los enlaces covalentes suele requerir luz ultravioleta. El proyecto financiado con fondos europeos PADRE utilizará luz azul ultravioleta para desencadenar y controlar con precisión implantes de administración de medicamentos a demanda. El proyecto utilizará luz generada mediante conversión ascendente de fotones o fuentes lumínicas integradas. El primer método permitirá la conversión ascendente de aniquilación de triplete-triplete rojo-a-azul ultravioleta pionera y eficaz en un entorno de hidrogel. El segundo permitirá la generación de luz mediante una fuente de luz coimplantada.
Objetivo
This proposal introduces a next-generation platform for next generation optimally personalised drug therapy: on-demand drug releasing implants triggered and controlled by blue/UV light. The technology is based on novel light generation pathways and a light-sensitive nanocellulose drug reservoir.
A formidable physiological barrier for light-triggered drug release has been the inability to use high-energy blue/UV light as the triggering signal. This is because the penetration depth of light drops to from a few cm to under 100 micrometers when moving from near-infrared to UV light, making deeper targets within tissues accessible only to red light. However, red light, with its intrinsically lower energy, has limited value in photochemical reactions because the photocleavage of covalent bonds typically requires UV-light. This is why many groups are looking at e.g. red-to-blue photon upconversion strategies. The major objective in PADRE is to circumvent the issue of unavailable blue light in implants through local light generation. Having access to light with higher energy will enable a much wider chemical toolbox, including photocleavable linkers.
I will use blue/UV light to trigger and precisely control drug release. The approach creates an unconventional way to modulate the release profiles without unwanted drug leakage. The light will be generated through either 1) photon upconversion, or 2) integrated light sources. With the first approach, I will pioneer efficient red-to-blue/UV triplet-triplet annihilation upconversion in a hydrogel environment, while in the second approach I will generate light by a co-implanted light source. Both approaches are feasible according to my preliminary results on efficient triplet-triplet annihilation upconversion and photoresponsive liposomes and will be demonstrated in a working implant prototype. The core breakthrough of PADRE will be a viable solution to employ blue excitation in precisely-tailored drug-releasing implants.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
00014 Helsingin Yliopisto
Finlandia