Site-Specific Prodrug Release Using Visible Light

Abstract

Approach Summary Licensing status Publication and contact information Drug delivery Photodynamic prodrug release system using visible light A nonenzymatic, photodynamic prodrug system could provide better control over drug delivery than systems that release drugs by enzymatic activation. With the new system, drugs bearing carbonyl groups were attached to a photosensitizer that allowed drug release upon visible light irradiation. Methyl esters of non-steroidal anti-inflammatory drugs (ibuprofen and naproxen) were linked to photosensitized porphyrin derivatives and within minutes were released by visible light illumination in high yields in vitro. Next steps were not disclosed. QLT Inc. and Novartis AG market Visudyne verteporfin photodynamic therapy to treat wet age-related macular degeneration. No fewer than six other companies have photodynamic therapies for multiple indications in developmental stages ranging from preclinical to marketed. Patent and licensing status undisclosed Jiang, M. et al.

Emerging Strategies for Controlling Drug Release by Using Visible/Near IR Light

“…It is proposed that this fiber optics-guided delivery of oxygen and PSs could be applied to hypoxic conditions. Activation of prodrugs by an SO-cleavable linker was demonstrated by Jiang et al [48] and Bio et al [49]. One of the key requirements of prodrugs is the release of the parent drug without any modification to drug structure.…”

“…One of the key requirements of prodrugs is the release of the parent drug without any modification to drug structure. Thus, Jiang et al conjugated a PS to a drug, bearing a carbonyl group through an SO-labile linker (Scheme 4a) [48]. Irradiation cleaved the SO-labile linkers releasing free drugs.…”

Photochemical Transformations Involving Porphyrins and Phthalocyanines

“…However, its quantum yield for singlet oxygen generation in liposomes (0.023) is much lower than that of Photofrin (0.19) (Gross et al 1993). Other examples are zinc, palladium, copper and free-base porphyrin complexes of 5-(4-(trimethylammonium)phenyl)-10,15,20-tris(2,4,6-trimethoxyphenyl)porphyrin iodide (Milanesio et al 2008) or compounds with photocleavable linkers as photodynamic prodrug systems (Bakar et al 2009, Jiang andDolphin 2008). Note, that zinc derivatives are not necessarily the best metal derivatives of phthalocyanines for use in PDT (Canti et al 1992).…”

A novel visible light responsive nanosystem for cancer treatment

“…It has been reported the spontaneous cleavage of aminoacrylates (β-enamino esters) following 2+2 cycloaddition reactions of singlet oxygen with olefins for the site-specific release of bioactive molecules. 26 Herein, we propose and demonstrate an innovative approach to design a new Vis light-responsive drug delivery nanosystem. To this aim, the pore outlets of drug-loaded MSN are blocked via sol-gel chemistry by grafting silylated porphyrin nanocaps incorporating ROS-cleavable bonds, which have been carefully designed and whose synthesis has been optimized in this work.…”