Novel Biodegradable Fluorescent Copolymer Anhydride Synthesis, Characterization And Application

Polyanhydrides have been widely used in biomedical field due to their good biocompatibility and biodegradability. In our previous works, we initially found a class of polyanhydrides displaying strong fluorescent properties with the excitation of ultraviolet (UV) or visible light, such as poly(p-(carboxyethylformamido) benzoic anhydride) (PCEFB) and poly(p-carboxy phenyl succinic monoester anhydride) (PCPS). The chemical structure of the polyanhydrides is like [OC(O)ArXC(O)(CH2)2C(O)]m, where Ar was (substituted) phenylene and X was O or NH. The maximum emission wavelength varies with the excitation wavelength, 480 and 520 nm with the excitation wavelength at 470 nm and 430 nm at 356 nm. Copolyanhydrides containing the fluorophoric diacid can also emit fluorescence. In this paper, CPP was selected as co-monomer for copolymerizing with CEFB in order to modulate the degradation rate of the fluorescent polyanhydrides since PCPP has been approved to be biocompatible and its degradation duration can be up to several years. In addition, a novel types of fluorescent poly(anhydride-ester), poly(di(p-carboxyphenyl) succinate anhydride) (P(dCPS)), which has similar structure to PCPS, was synthesized with a very convenient scheme and high yield. The polymers can also emit strong fluorescence with the excitation of ultraviolet (UV) or visible light. And the maximum emission wavelength is 410 nm with an excitation wavelength at 327 nm, and 476 and 510 nm at 462 nm. The degradation rate can be modulated from several days to months simply by copolymerization with sebacic acid.Our work includes two parts:Part I: Synthesis, characterization and degradation of a novel class of fluorescent poly[1,3-bis(p-carboxyphenoxy) propane: p-(carboxyethylformamido) benzoic anhydride] (P(CPP:CEFB))One class of fluorescent copolyanhydrides were synthesized by melt copolycondensation of the fluorophoric diacid, p-(carboxyethylformamido)benzoic acid (CEFB), with 1,3-bis(p-carboxyphenoxy) propane (CPP). 1HNMR spectra of the copolymers confirm their chemical structures. All the copolymers can give off fluorescence with the excitation of both UV (356 nm) and visible light (470 nm). Thefluorescence intensity increases with an increase in CEFB fraction. The degradation rate of the copolyanhydrides can be modulated by the polymer components, increasing with a decrease in CPP content. In addition, CEFB segments in the copolymers degraded rapider than CPP segments, resulting in an increase in CPP fraction in the degraded copolyanhydrides. Morphology change of the copolyanhydrides during degradation was also examined by SEM. It was found that the outer layers of the degraded samples erode faster than the inner layers. Fluorescence intensity of the degraded copolyanhydrides diminished with time.Part II: Novel Polyanhydrides Combining Strong Inherent Fluorescence and Wide Biodegradability: Synthesis, Characterization and in vitro DegradationA novel diacid monomer which is derived from natural-occurring products and can emit strong fluorescence when polymerizes to polyanhydride was synthesized with a very convenient scheme. Chemical structure of the monomer is like HOC(O)ArOC(O)(CH2)2C(O)OArC(O)OH (dCPS). Copolyanhydrides composed of dCPS and sebacic acid (SA) were further prepared by melt copolycondensation and characterized by IR, NMR, UV-Vis, DSC and fluorometer. The emission wavelength ( em) of the copolymers could be tuned by the excitation wavelength ( ex). Fluorescence intensity increased with an increase in dCPS content. The microspheres fabricated from the copolymer with dCPS content as low as 10% could be clearly visualized with fluorescence microscopy. Either blue or green images of the microspheres could be captured with an excitation of UV and visible light. Degradation rate of the copolyanhydrides decreased as dCPS fraction increased, and the degradation duration could be modulated from several days to more than three months. In addition, it was found that the copolyanhydrides displayed typical surface-degradation characteristics. The advantages of...