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
To ensure the delivery of antitumor drugs to tumor site and quick release in tumor cells, we designed and prepared pH-sensitive polymeric micelles by combining cationic ring-opening polymerization of 2-ethyl-2-oxazoli...To ensure the delivery of antitumor drugs to tumor site and quick release in tumor cells, we designed and prepared pH-sensitive polymeric micelles by combining cationic ring-opening polymerization of 2-ethyl-2-oxazoline （EOz） with vitamin E succinate （VES）, and then encapsulating paclitaxel （PTX） into the micelles self-assembled by poly（2-ethyl-2-oxazoline）-vitamin E succinate （PEOz-VES）. The structure of the synthesized PEOz-VES was confirmed by ^1H NMR spectrum, and the molecular weight measured by GPC was 1212 g/mol. The pKa of PEOz-VES with a low critical micelle concentration of （5.84±0.02） mg/L was determined to be 6.01. The PTX-loaded PEOz-VES polymeric micelles prepared by film hydration method were characterized to have a nanoscaled size of about 30 nm in diameter, a positive Zeta potential of 4.86 mV and uniform spherical morphology by TEM observation. The drug loading content and encapsulation efficiency were （2.63±0.16）% and （84.1±3.38）%, respectively. The in vitro release behavior of PTX from PEOz-VES micelles in PBS displayed pH-dependent pattern and was gradually accelerated with decrease of pH value, implying that the micelles could distinguish endo/lysosomal pH and tumor extracellular pH from physiological pH by accelerating drug release. Therefore, the designed PEOz-VES micelles might have significant promise for anti-cancer drug delivery.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, 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 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 ensure the delivery of antitumor drugs to tumor site and quick release in tumor cells, we designed and prepared pH-sensitive polymeric micelles by combining cationic ring-opening polymerization of 2-ethyl-2-oxazoline （EOz） with vitamin E succinate （VES）, and then encapsulating paclitaxel （PTX） into the micelles self-assembled by poly（2-ethyl-2-oxazoline）-vitamin E succinate （PEOz-VES）. The structure of the synthesized PEOz-VES was confirmed by ^1H NMR spectrum, and the molecular weight measured by GPC was 1212 g/mol. The pKa of PEOz-VES with a low critical micelle concentration of （5.84±0.02） mg/L was determined to be 6.01. The PTX-loaded PEOz-VES polymeric micelles prepared by film hydration method were characterized to have a nanoscaled size of about 30 nm in diameter, a positive Zeta potential of 4.86 mV and uniform spherical morphology by TEM observation. The drug loading content and encapsulation efficiency were （2.63±0.16）% and （84.1±3.38）%, respectively. The in vitro release behavior of PTX from PEOz-VES micelles in PBS displayed pH-dependent pattern and was gradually accelerated with decrease of pH value, implying that the micelles could distinguish endo/lysosomal pH and tumor extracellular pH from physiological pH by accelerating drug release. Therefore, the designed PEOz-VES micelles might have significant promise for anti-cancer drug delivery.
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.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.
