Two-photon absorption-controlled multidose drug release: a novel approach for secondary cataract treatment

Abstract

Tens of millions of cataract surgeries are done every year and the number is increasing heavily. Posterior capsule opacification is the major postoperative complication with an incidence of 10 to 50% within 5 years, depending on the age of the patient. We present a novel approach for secondary cataract treatment in a noninvasive manner. Photochemically triggered drug release from a polymer enables repeated drug applications for cataract treatment years after implantation of the intraocular lens, just when needed. However, light in the visible spectral range must pass through the lens but must not induce drug release. We demonstrate that two-photon absorption photochemistry is a powerful tool to overcome this problem. With wavelengths in the visible regime, a photochemical reaction that requires energies in the UV is triggered. The high intensities needed for this process never occur in any lighting condition in daily lives, but may be easily obtained with focused laser beams routinely used in ophthalmology. The properties of the therapeutic system are specified and the function is demonstrated by in-vitro cell tests. Noninvasive multidose photochemically triggered drug release from implanted intraocular lenses carrying a drug depot may be a therapeutic as well as an economic choice to established treatments of secondary cataracts.

A Polymeric Drug Depot Based on 7‐(2′‐Methacryloyloxyethoxy)‐4‐methylcoumarin Copolymers for Photoinduced Release of 5‐Fluorouracil Designed for the Treatment of Secondary Cataracts

“…1-Heptanoyl-5-fluorouracil (H5FU) (5) was synthesized starting with 5-fluorouracil (5FU) (7) according to a procedure described in the literature. [9,17] …”

“…[8][9][10][11][12] 5-Fluorouracil (5FU) is a well-studied chemotherapeutic agent and, recently, an interesting review article on the radiation and photoinduced activation of 5FU pro-drugs for selective treatment of cancers was published. [13] A pro-drug is a chemically modified form that is converted to the active form of the drug in the biological system and exerts its effect.…”

Two‐photon microscopy of deep intravital tissues and its merits in clinical research

“…Another implementation of 2-photon absorption called lens tuning to treat the poor visual performance after cataract surgery was reported by the same clinical research group (Kim et al, 2006;Träger et al, 2007). The refractive power of the implanted intraocular lens often does not have the value required for optimum vision.…”

“…Photochemistry triggered by 2-photon absorption opens up an interesting therapeutic approach to treat the posterior capsular opacification after cataract surgery and to avoid a secondary cataract in ophthalmology (Kim et al, 2006;Träger et al, 2007). The secondary cataract, taking place due to a posterior capsular opacification, always occurs after cataract surgery owning to the growth of epithelial cells over the face of the implanted artificial polymeric intraocular lens.…”

Short Electrospun Fibers by UV Cutting Method

“…PBMAOC was synthesized and characterized in accordance to the ref. [12,13] The copolymer composition of PBMAOC (n-butylmethacrylate/coumarin containing units) used in this work was 9-1 (molar ratio). The molecular weight (M n ) of polymer was about 100 000.…”