This study aimed to explore the link between block copolymers’interfacial properties and nanoscale carrier formation and found out the influence of length ratio on these characters to optimize drug delivery system.A ...This study aimed to explore the link between block copolymers’interfacial properties and nanoscale carrier formation and found out the influence of length ratio on these characters to optimize drug delivery system.A library of diblock copolymers of PEG-PCL and triblock copolymers with additional PEI(PEG-PCL-PEI)were synthesized.Subsequently,a systematic isothermal investigation was performed to explore molecular arrangements of copolymers at air/water interface.Then,structural properties and drug encapsulation in self-assembly were investigated with DLS,SLS and TEM.We found the additional hydrogen bond in the PEG-PCL-PEI contributes to film stability upon the hydrophobic interaction compared with PEG-PCL.PEG-PCL-PEI assemble into smaller micelle-like(such as PEGPCL4006-PEI)or particle-like structure(such as PEG-PCL8636-PEI)determined by their hydrophilic and hydrophobic block ratio.The distinct structural architectures of copolymer are consistent between interface and self-assembly.Despite the disparity of constituent ratio,we discovered the arrangement of both chains guarantees balanced hydrophilic-hydrophobic ratio in self-assembly to form stable construction.Meanwhile,the structural differences were found to have significant influence on model drugs incorporation including docetaxel and siRNA.Taken together,these findings indicate the correlation between molecular arrangement and self-assembly and inspire us to tune block compositions to achieve desired nanostructure and drug loading.展开更多
To improve the oral absorption of poorly water-soluble drugs by overcoming the intestinal epithelium barrier, calcium carbonate nanoparticles targeting to intestine peptide transporter 1(Pep T1) were fabricated by m...To improve the oral absorption of poorly water-soluble drugs by overcoming the intestinal epithelium barrier, calcium carbonate nanoparticles targeting to intestine peptide transporter 1(Pep T1) were fabricated by modification of the surface of calcium carbonate nanoparticles with Gly-Sar. Gly-Sar-conjugated TPGS was successfully synthesized and characterized, and coumarin 6-loaded Gly-Sar modified calcium carbonate nanoparticles were then prepared and characterized to have a nano-scaled size of about 193 nm in diameter, cracked surface morphology under a scanning electron microscope, and high drug loading efficiency(60.5±5.9)%. Moreover, the Gly-Sar-modified calcium carbonate nanoparticles exhibited better drug loading stability during the process of their transcellular transport, and evidently enhanced intestinal absorption of poorly water-soluble agents. Therefore, the designed intestine Pep T1-targeted calcium carbonate nanoparticles might have a promising potential for oral delivery of poorly water-soluble drugs.展开更多
The intestinal epithelium is the main barrier to the oral delivery of poorly water-soluble drugs. Based on the specific transporters expressed on the apical membrane of the intestinal epithelium, novel polymer micelle...The intestinal epithelium is the main barrier to the oral delivery of poorly water-soluble drugs. Based on the specific transporters expressed on the apical membrane of the intestinal epithelium, novel polymer micelles targeting to the organic cation transporter 2(OCTN2) were constructed by combining carnitine conjugated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)(Car-PEOz-PLA) with monomethoxy poly(ethylene glycol)-poly(D,L-lactide)(mP EG-PLA). The structure of the synthesized Car-PEOz-PLA was confirmed by -1H NMR, TLC and ammonium reineckate precipitation reaction, and the number-average molecular weight determined by GPC was 7260 g/mol with a low PDI of 1.44. Coumarin 6-loaded carnitine modified polymeric micelles prepared by film hydration method were characterized to have a nano-scaled size of about 31 nm in diameter, uniform spherical morphology, high drug loading content of 0.098%±0.03% and encapsulation efficiency of 92.67%±2.80%. Moreover, the carnitine-modified micelles exhibited the similar in vitro release behavior in SGF and SIF, and evidently enhanced intestinal absorption of poorly water-soluble agent. Therefore, the designed OCTN2-targeted micelles might have a promising potential for oral delivery of poorly water-soluble drugs.展开更多
In the present study,a total of 11 compounds were isolated from the aerial parts of Glycyrrhiza uralensis,including two new compounds,glycyuralin Q(1)and glycyuralin R(2),and nine known compounds,including licoripheno...In the present study,a total of 11 compounds were isolated from the aerial parts of Glycyrrhiza uralensis,including two new compounds,glycyuralin Q(1)and glycyuralin R(2),and nine known compounds,including licoriphenone(3),orobol(4),trifoliol(5),7,2′,4′-trihydroxy-5-methoxy-3-arylcoumarin(6),11-hydroxy-9(Z),12(Z)-octadecadienoic acid(7),11-hydroxy-9(E),12(E)-octadecadienoic acid(8),licoricone(9),glycyrin(10),and 2′-hydroxyformononetin(11).Structures of the new compounds were identified by 1 D,2 D NMR and HR-MS data analyses.Compounds 1,2 and 10 showed potent inhibitory activities against PTP1 B,with IC50 values of 1.43,4.71 and 3.79μM,respectively.Compounds 2,4 and 10 inhibitedα-glucosidase with IC50 values of 13.61,11.13 and 17.48μM,respectively.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
基金the NSFC(Nos.81673365,81973258 and 81473156,China)the Fangzheng Foundation(China)for funding of the work
文摘This study aimed to explore the link between block copolymers’interfacial properties and nanoscale carrier formation and found out the influence of length ratio on these characters to optimize drug delivery system.A library of diblock copolymers of PEG-PCL and triblock copolymers with additional PEI(PEG-PCL-PEI)were synthesized.Subsequently,a systematic isothermal investigation was performed to explore molecular arrangements of copolymers at air/water interface.Then,structural properties and drug encapsulation in self-assembly were investigated with DLS,SLS and TEM.We found the additional hydrogen bond in the PEG-PCL-PEI contributes to film stability upon the hydrophobic interaction compared with PEG-PCL.PEG-PCL-PEI assemble into smaller micelle-like(such as PEGPCL4006-PEI)or particle-like structure(such as PEG-PCL8636-PEI)determined by their hydrophilic and hydrophobic block ratio.The distinct structural architectures of copolymer are consistent between interface and self-assembly.Despite the disparity of constituent ratio,we discovered the arrangement of both chains guarantees balanced hydrophilic-hydrophobic ratio in self-assembly to form stable construction.Meanwhile,the structural differences were found to have significant influence on model drugs incorporation including docetaxel and siRNA.Taken together,these findings indicate the correlation between molecular arrangement and self-assembly and inspire us to tune block compositions to achieve desired nanostructure and drug loading.
基金The National Natural Science Foundation of China(Grant No.81673366)the National Key Science Research Program of China(973 Program,Grant No.2015CB932100)
文摘To improve the oral absorption of poorly water-soluble drugs by overcoming the intestinal epithelium barrier, calcium carbonate nanoparticles targeting to intestine peptide transporter 1(Pep T1) were fabricated by modification of the surface of calcium carbonate nanoparticles with Gly-Sar. Gly-Sar-conjugated TPGS was successfully synthesized and characterized, and coumarin 6-loaded Gly-Sar modified calcium carbonate nanoparticles were then prepared and characterized to have a nano-scaled size of about 193 nm in diameter, cracked surface morphology under a scanning electron microscope, and high drug loading efficiency(60.5±5.9)%. Moreover, the Gly-Sar-modified calcium carbonate nanoparticles exhibited better drug loading stability during the process of their transcellular transport, and evidently enhanced intestinal absorption of poorly water-soluble agents. Therefore, the designed intestine Pep T1-targeted calcium carbonate nanoparticles might have a promising potential for oral delivery of poorly water-soluble drugs.
基金The National Natural Science Foundation of China(Grant No.81673366)the National Key Science Research Program of China(973 Program,Grant No.2015CB932100)
文摘The intestinal epithelium is the main barrier to the oral delivery of poorly water-soluble drugs. Based on the specific transporters expressed on the apical membrane of the intestinal epithelium, novel polymer micelles targeting to the organic cation transporter 2(OCTN2) were constructed by combining carnitine conjugated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)(Car-PEOz-PLA) with monomethoxy poly(ethylene glycol)-poly(D,L-lactide)(mP EG-PLA). The structure of the synthesized Car-PEOz-PLA was confirmed by -1H NMR, TLC and ammonium reineckate precipitation reaction, and the number-average molecular weight determined by GPC was 7260 g/mol with a low PDI of 1.44. Coumarin 6-loaded carnitine modified polymeric micelles prepared by film hydration method were characterized to have a nano-scaled size of about 31 nm in diameter, uniform spherical morphology, high drug loading content of 0.098%±0.03% and encapsulation efficiency of 92.67%±2.80%. Moreover, the carnitine-modified micelles exhibited the similar in vitro release behavior in SGF and SIF, and evidently enhanced intestinal absorption of poorly water-soluble agent. Therefore, the designed OCTN2-targeted micelles might have a promising potential for oral delivery of poorly water-soluble drugs.
基金National Natural Science Foundation of China(Grant No.81891010/81891011)National Mega-project for Innovative Drugs(Grant No.2018ZX09711001-008-003)Science&Technology Department of Xinjiang Uygur Autonomous Region(Grant No.2018AB012).
文摘In the present study,a total of 11 compounds were isolated from the aerial parts of Glycyrrhiza uralensis,including two new compounds,glycyuralin Q(1)and glycyuralin R(2),and nine known compounds,including licoriphenone(3),orobol(4),trifoliol(5),7,2′,4′-trihydroxy-5-methoxy-3-arylcoumarin(6),11-hydroxy-9(Z),12(Z)-octadecadienoic acid(7),11-hydroxy-9(E),12(E)-octadecadienoic acid(8),licoricone(9),glycyrin(10),and 2′-hydroxyformononetin(11).Structures of the new compounds were identified by 1 D,2 D NMR and HR-MS data analyses.Compounds 1,2 and 10 showed potent inhibitory activities against PTP1 B,with IC50 values of 1.43,4.71 and 3.79μM,respectively.Compounds 2,4 and 10 inhibitedα-glucosidase with IC50 values of 13.61,11.13 and 17.48μM,respectively.
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.