Synthesis, Characterization, and Properties Evaluation of Methylcoumarin End-Functionalized Poly(methyl methacrylate) for Photoinduced Drug Release

Abstract

The synthesis of novel methylcoumarin end-functionalized poly(methyl methacrylate) of different molecular weights using atom transfer radical polymerization (ATRP) is reported. 7-(2′-Bromoisobutyryloxy)-4-methylcoumarin was used as the ATRP initiator at 70 °C using copper(I) bromide/1,1,4,7,7-pentamethyldiethylenetriamine (PMDETA) as the catalyst system. The theoretical and experimental number-average molecular weights Mn with narrow polydispersities (Mw/Mn = 1.1−1.4) agreed very well. Photochemical drug loading of the methylcoumarin end-functionalized polymer was performed in solution (chloroform/acetone 1:2) with benzophenone as additional photosensitizer using a 50-fold excess of the pro-drug 1-heptanoyl-5-fluorouracil (H5FU). UV/vis and NMR spectroscopy were used for the characterization of the polymer drug conjugate and indicated an almost quantitative conversion of coumarin moieties into photodimers. The change of polymer properties like thermal stability, glass transition, and molecular weight after photochemical drug immobilization was also studied. The glass transition temperature increased only negligibly, whereas the thermal decomposition commenced at considerably lower temperature for the polymer drug conjugate. The molecular weight distribution of the H5FU-loaded polymer showed no detectable chain degradation due to the applied UV irradiation. The characterization of the photoinduced drug release was investigated for a single photon absorption (SPA) process. The polymer drug conjugate was irradiated at λ = 266 nm to cleave the cyclobutane linker between the methylcoumarin moiety and the pro-drug H5FU. The drug release was monitored and quantified using high-performance liquid chromatography (HPLC). Assuming quantitative hydrolysis of H5FU, 4.76 µg of 5-fluorouracil (5FU) per 1 mg of polymer drug conjugate was released on irradiation.