Preparation of photolabile nanoparticles by coumarin-based crosslinker for drug delivery under light irradiation

Doxorubicin is (DOX) a hydrophobic cancer drug which can be encapsulated inside polymeric drug carriers to grant a prolonged circulation of DOX in blood. Moreover, sufficient stability of drug nanocarriers during their circulation time in blood flow is essential for efficient drug delivery and low cytotoxicity. However, destabilization of these drug carriers and efficient drug release in a spatiotemporal fashion when they reach target tissues. Herein, we have developed a new type of nanocarriers with photolabile crosslinker responding to UV light by complete cleavage of drug carriers that allows for active delivery of anticancer drug regulated by external photo-irradiation. Photolabile nanocarriers are synthesized in one step via distillation precipitation polymerization (DPP) of 2-hydroxyethyl methacrylate (HEMA) with the new photolabile crosslinker. This crosslinker is head-totail 7-(allyloxy)-4-methyl-2H-chromen-2-one dimer obtained by photodimerization of 7-(allyloxy)-4-methyl-2Hchromen-2-one which is prepared from 7-hydroxy-4-methylcoumarin and characterized using H-1 NMR, ATR-FTIR, UV-vis-NIR spectrophotometer, fluorescence spectroscopy, Ubbelohde capillary viscometer, and fluorescence microscopy. The shape and size of the resultant nanoparticles are investigated by means of FE-SEM images and their particle sizes are confirmed by dynamic light scattering (DLS). Prepared drug carriers are loaded with DOX and drug release behavior is observed at different conditions. Drug release studies indicated that photolabile nanoparticles showed excellent cumulative drug release during 48 h at acidic pH as found to be 93.2 +/- 2.1 and 96.8 +/- 1.7% for drug carriers with 10 and 15 mol. % photolabile crosslinker, respectively. Furthermore, due to less drug aggregation, photolabile crosslinked nanoparticles showed higher drug loading efficiency (DLE, 42-49%) than MBA crosslinked particles (DLE, 32-37%).