UV-cleavable unimolecular micelles: Synthesis and characterization toward photocontrolled drug release carriers

UV-cleavable star polymers composed of a well-defined 6-arm amphiphilic block copolymer and a UV-cleavable core with photolabile o-nitrobenzyl groups have been synthesized and characterized. The core of the star polymer is a cyclotriphosphazene, which can biodegrade to phosphate and ammonium ion. The resultant unimolecular micelles can be dissociated in a controlled manner by UV irradiation. The inner lipophilic poly(methyl methacrylate) (PMMA) and the outer hydrophilic poly[poly(ethylene glycol) methyl ether methacrylate] (PPEGMA) were grafted by atom transfer radical polymerization (ATRP), leading to the formation of star-PMMA-PPEGMA with different compositions. The effects of various factors, such as molecular weight, solution concentration, solvents (THF, toluene, and water) and monomers (MMA, PEGMA, and 2-(dimethylamino)ethyl methacrylate (DMA)) on the photodegradation rate of the star polymers were studied by gel permeation chromatography (GPC). The micellar behavior of star-PMMA-PPEGMA was unambiguously demonstrated by dynamic light scattering (DLS), fluorescence techniques and transmission electron microscopy (TEM). The formation of nanoparticles (star-AGG) from the aggregation of the two star-PMMA-PPEGMA polymer micelles in aqueous solution was detected by DLS with hydrodynamic radii of 86 and 111 nm. The critical aggregation concentration (CAC) of star-AGG-2 from star-PMMA₁₇₉-PPEGMA₈₉-2 was 0.0026 g L^-1 and 0.022 g L^-1 before and after UV-irradiation indicating the reduced stability of the polymer micellar structures after UV-irradiation due to the detachment of the amphiphilic arms from the cyclotriphosphazene core. As a result, spontaneous dissociation of cleaved micelles can be induced by the dilution effect in the human body for stimulus-controlled drug release.