Synthesis and characterization of fluorescein isothiocyanate (FITC)-labeled PEO-PCL-PEO triblock copolymers for topical delivery

We present the synthesis of fluorescein isothiocyanate (FITC)-labeled poly(ethylene oxide)-block-poly(epsilon-caprolactone)-block-poly(ethylene oxide) (PEO-PCL-PEO) triblock copolymers and their applications for tracking the penetration behavior of FITC-labeled copolymers in the hairless mouse skin. In the first step, PEO-PCL diblock copolymers with different ratios of PCL to PEO (i.e., [CL]/[EO]) were prepared by ring opening polymerization of epsilon-caprolactone (CL), where monomethoxy poly(ethylene glycol) (mPEG, M-n = 2000 g mol(-1)) was used as a macro-initiator. FITC was successively reacted with octadecylamine. isophorone diisocyanate (IPDI), and then used as a linker to obtain PEO-PCL-PEO triblock copolymers from the PEO-PCL diblock copolymers. In aqueous solution, both FITC-labeled triblock copolymers show two UV absorption peaks at 489 and 455 nm, attributed to the monomeric FITC and H-aggregated FITC moieties, respectively. Due to the strong H-aggregation of FITC in the copolymer of high [CL]/[EO], fluorescent emission intensities considerably decreased at high concentrations of the copolymer. FITC-labeled copolymers exhibited more sharper polarized optical and fluorescence microscopic images compared to the mixtures of FITC and unlabeled copolymer in both solid crystalline and multiple emulsion state. Furthermore, the Frantz diffusion cell test was carried out to demonstrate the penetration behavior of the FITC-labeled copolymers in the hairless mouse skin. (C) 2009 Elsevier Ltd. All rights reserved.