Two-photon absorption triggered drug delivery from a polymer for intraocular lenses in presence of an UV-absorber

Two-photon-absorption (TPA) triggered photochemistry is a versatile tool to photochemically release compounds in an uncaging reaction where the desired reaction should occur behind an UV absorbing barrier, e.g. as in intraocular lenses (IOLs). Nonlinear effects of the UV-absorbing barrier, in this case the cornea, are negligible as long as the laser light passes through it at an intensity low enough that nonlinear effects do not occur. Only in the focus of the beam, i.e. inside the IOL, the required intensities are reached and TPA triggered photo cleavage occurs. The situation becomes complicated as soon as UV-absorbers are admixed to the polymer material. We show that typical concentrations of an UV-absorber only slightly affect the TPA-triggered uncaging reaction rate. As a testbed we used a newly synthetized acrylic polymer derivatized with an o-nitrobenzyl linker group carrying 5-fluorouracil as the model drug to be released. No photochemical decomposition of the UV absorber was observed. The release rate of 5-fluorouracil in presence of the UV absorber was reduced by about 6% only. Further the polymer presented here, is the first to release unmodified 5-fluorouracil without any auxiliary groups attached. This is important for potential applications in humans.

► Synthesis of a photo active monomer with o-nitrobenzyl-5FU moiety for drug delivery. ► SPA quantum yield results to 0.27 and TPA cross-section is calculated to 2.41 GM. ► TPA induced drug delivery in presence of an UV-absorber is shown. ► TPA induced drug delivery from prototype intraocular lens is shown.