In order to improve the cancer-targeting and selective activity of antineoplastic agent [5-fluorouracil （5-FU）], a novel pH-responsive drug delivery system [pullulan acetate/sulfonamide （PA/SDM） conjugate] was syn...In order to improve the cancer-targeting and selective activity of antineoplastic agent [5-fluorouracil （5-FU）], a novel pH-responsive drug delivery system [pullulan acetate/sulfonamide （PA/SDM） conjugate] was synthesized by a diafiltration method. Sulfonamide was grafted to the hydrophobicaUy modified pullulan acetate to enhance the pH sensitivity for better cancer-targeting delivery. 5-FU was loaded into the self-assembled nanoparticles by the same method. The drug-loaded self-assembled nanoparticles were successfully obtained and characterized in terms of particle size, morphology and drug loading and release profile at various pHs. The results showed that the mean diameter of the self-assembled particles was approximately 100nm, with uniform size and good spherical morphology. The nanoparticles showed good stability at pH 7.4, which is equal to that of the normal body fluid, but shrank and aggregated below pH 6.8, which is close to the pH with tumors. The loading efficiency and concentration of released 5-FU was monitored at 269 nm on the UVNis spectrophotometer. The release profile was heavily pH-dependent around phvsiological pH, and the release rate was significantly enhanced under pH of 6.8.展开更多
The aim of this work was to synthesize a pantoprazole-imprinted polymer(MIPs)and study its binding and release properties in an aqueous media.Methacrylic acid(MAA),methacrylamide(MAAM),hydroxyethyl methacrylate(HEMA),...The aim of this work was to synthesize a pantoprazole-imprinted polymer(MIPs)and study its binding and release properties in an aqueous media.Methacrylic acid(MAA),methacrylamide(MAAM),hydroxyethyl methacrylate(HEMA),and 4-vinyl pyridine(4VP)were tested as functional monomers.Different solvents were also applied as polymerization media under heat or UV radiation.The optimized MIP was prepared in chloroform as a solvent,4-vinyl pyridine as a functional monomer,and ethylene glycole dimethacrylate(EGDMA)as a crosslinker monomer under UV irradiation.Binding and release properties of MIP were studied in comparison with a non-imprinted polymer(NIP)in aqueous media,at different pH values.The protective effect of polymer for drugs against acidic conditions was evaluated at pH 2.Results indicated that the MIP had superior binding properties compared to NIP for pantoprazole.The percentage of drug released from MIP was significantly less than from NIP at all pH values,which was attributed to the presence of imprinted cavities in the MIP matrix.MIP also had a stronger protective effect for pantoprazole in acidic media,in comparison with NIP.展开更多
In the present study, we designed and fabricated pH-sensitive polymeric micelles based on the conjugate of poly（2-ethyl-2-oxazoline）-poly（D,L-lactide）（PEOz-PLA） with doxorubicin（PEOz-PLA-imi-DOX） to efficientl...In the present study, we designed and fabricated pH-sensitive polymeric micelles based on the conjugate of poly（2-ethyl-2-oxazoline）-poly（D,L-lactide）（PEOz-PLA） with doxorubicin（PEOz-PLA-imi-DOX） to efficiently inhibit tumor cell growth. Hence, PEOz-PLA-imi-DOX was successfully synthesized by connecting DOX to the hydrophobic end of pH-sensitive PEOz-PLA via acid cleavable benzoic imine linker and characterized by 1 H NMR spectrum and thin layer chromatography. The critical micelle concentration of PEOz-PLA-imi-DOX was determined to be（14.84±3.85） mg/L. The conjugate micelles（denoted as PP-DOX-PM） formed by PEOz-PLA-imi-DOX using film-hydration method were characterized to have a nano-scaled size of about 21 nm in diameter, and the drug loading content was 1.67%. PP-DOX-PM showed pH-dependent drug release behavior with gradually accelerated release of DOX with decrease of pH value, illustrating the micelles＇ distinguishing feature of endo/lysosomal pH from physiological pH by accelerating drug release. As anticipated, PP-DOX-PM maintained the cytotoxicity of DOX against MDA-MB-231 cells. Collectively, PP-DOX-PM might have great potential for effective suppression of tumor growth.展开更多
文摘In order to improve the cancer-targeting and selective activity of antineoplastic agent [5-fluorouracil （5-FU）], a novel pH-responsive drug delivery system [pullulan acetate/sulfonamide （PA/SDM） conjugate] was synthesized by a diafiltration method. Sulfonamide was grafted to the hydrophobicaUy modified pullulan acetate to enhance the pH sensitivity for better cancer-targeting delivery. 5-FU was loaded into the self-assembled nanoparticles by the same method. The drug-loaded self-assembled nanoparticles were successfully obtained and characterized in terms of particle size, morphology and drug loading and release profile at various pHs. The results showed that the mean diameter of the self-assembled particles was approximately 100nm, with uniform size and good spherical morphology. The nanoparticles showed good stability at pH 7.4, which is equal to that of the normal body fluid, but shrank and aggregated below pH 6.8, which is close to the pH with tumors. The loading efficiency and concentration of released 5-FU was monitored at 269 nm on the UVNis spectrophotometer. The release profile was heavily pH-dependent around phvsiological pH, and the release rate was significantly enhanced under pH of 6.8.
基金the Vice Chancellor of Research,Mashhad University of Medical Sciences,for financial support through Grant 89434
文摘The aim of this work was to synthesize a pantoprazole-imprinted polymer(MIPs)and study its binding and release properties in an aqueous media.Methacrylic acid(MAA),methacrylamide(MAAM),hydroxyethyl methacrylate(HEMA),and 4-vinyl pyridine(4VP)were tested as functional monomers.Different solvents were also applied as polymerization media under heat or UV radiation.The optimized MIP was prepared in chloroform as a solvent,4-vinyl pyridine as a functional monomer,and ethylene glycole dimethacrylate(EGDMA)as a crosslinker monomer under UV irradiation.Binding and release properties of MIP were studied in comparison with a non-imprinted polymer(NIP)in aqueous media,at different pH values.The protective effect of polymer for drugs against acidic conditions was evaluated at pH 2.Results indicated that the MIP had superior binding properties compared to NIP for pantoprazole.The percentage of drug released from MIP was significantly less than from NIP at all pH values,which was attributed to the presence of imprinted cavities in the MIP matrix.MIP also had a stronger protective effect for pantoprazole in acidic media,in comparison with NIP.
基金National Natural Science Foundation of China(Grant No.81673366)the National Key Science Research Program of China(973 Program,Grant No.2015CB932100)
文摘In the present study, we designed and fabricated pH-sensitive polymeric micelles based on the conjugate of poly（2-ethyl-2-oxazoline）-poly（D,L-lactide）（PEOz-PLA） with doxorubicin（PEOz-PLA-imi-DOX） to efficiently inhibit tumor cell growth. Hence, PEOz-PLA-imi-DOX was successfully synthesized by connecting DOX to the hydrophobic end of pH-sensitive PEOz-PLA via acid cleavable benzoic imine linker and characterized by 1 H NMR spectrum and thin layer chromatography. The critical micelle concentration of PEOz-PLA-imi-DOX was determined to be（14.84±3.85） mg/L. The conjugate micelles（denoted as PP-DOX-PM） formed by PEOz-PLA-imi-DOX using film-hydration method were characterized to have a nano-scaled size of about 21 nm in diameter, and the drug loading content was 1.67%. PP-DOX-PM showed pH-dependent drug release behavior with gradually accelerated release of DOX with decrease of pH value, illustrating the micelles＇ distinguishing feature of endo/lysosomal pH from physiological pH by accelerating drug release. As anticipated, PP-DOX-PM maintained the cytotoxicity of DOX against MDA-MB-231 cells. Collectively, PP-DOX-PM might have great potential for effective suppression of tumor growth.
