目的合成聚乙二醇单甲醚-聚乳酸(mPEG-PDLLA)嵌段共聚物,制备去氧鬼臼毒素mPEG-PDLLA嵌段共聚物(DPT-PM),提高去氧鬼臼毒素在水中的溶解度。方法以开环聚合反应合成mPEG-PDLLA,并通过IR、1H-HMR确证其结构,芘荧光探针法测定其临界胶束浓...目的合成聚乙二醇单甲醚-聚乳酸(mPEG-PDLLA)嵌段共聚物,制备去氧鬼臼毒素mPEG-PDLLA嵌段共聚物(DPT-PM),提高去氧鬼臼毒素在水中的溶解度。方法以开环聚合反应合成mPEG-PDLLA,并通过IR、1H-HMR确证其结构,芘荧光探针法测定其临界胶束浓度(CMC);采用溶剂蒸发法制备DPT-PM溶液,并将其冷冻干燥;分别采用动态光散射法(DLS)、透射电子显微镜(TEM)、差示扫描量热法(DSC)、高效液相色谱法(HPLC)等手段对胶束形态、粒径与分布、载药量、包封率等进行表征,并采用透析法考察DPT-PM体外释放,并对释放机制进行探讨。结果制备了去氧鬼臼毒素共聚物胶束,透射电镜下观察为近球形,平均粒径为22.0±8.9nm,载药量为20.67%,包封率为99.63%。结论 m PEG-PDLLA聚合物胶束可作为疏水性药物去氧鬼臼毒素的载体,具有较高的载药性能,能一定程度提高去氧鬼臼毒素在水中的溶解度。展开更多
Engineering small-molecule drugs into nanoparticulate formulations provides an unprecedented opportunity to improve the performance of traditional chemo drugs,but suffers from poor compatibility between drugs and nano...Engineering small-molecule drugs into nanoparticulate formulations provides an unprecedented opportunity to improve the performance of traditional chemo drugs,but suffers from poor compatibility between drugs and nanocarriers.Stimuli-responsive mPEG-PDLLA–drug conjugate-based nanomedicines can facilitate the exploitation of beneficial properties of the carrier and enable the practical fabrication of highly efficacious self-assembled nanomedicines.However,the influence of hydrophobic length on the performance of this type of nanomedicine is little known.Here we synthesized two acid-sensitive ketal-linked mPEG-PDLLA–docetaxel prodrugs with different lengths of PDLLA,and engineered them into self-assembled sub-20 nm micellar nanomedicines for breast cancer chemotherapy.We found that the nanomedicine consisting of a mPEG-PDLLA–docetaxel prodrug with the shorter length of PDLLA stood out due to its potent cytotoxicity,deep penetration into multicellular spheroids,and improved in vivo anticancer performance.Additionally,our prodrug-based nanomedicines outperformed the generic formulation of commercial Nanoxel in terms of safety profile,tolerated doses,and tumor suppression.Our findings indicate that the hydrophobic content of a polymeric prodrug nanomedicine plays an important role in the performance of the nanomedicine,and should be instructive for developing polymeric prodrug-based nanomedicines with clinical translational potential.展开更多
Injectable filling material is a simple and efficient method for soft tissues reconstruction and is extremely popular in not only plastic surgery but also cosmetic industry.However,there is a lack of soft tissue fille...Injectable filling material is a simple and efficient method for soft tissues reconstruction and is extremely popular in not only plastic surgery but also cosmetic industry.However,there is a lack of soft tissue fillers with perfect performance on the market currently.Here,we constructed a new microsphere/hydrogel composite and evaluated its potential as a candidate for soft tissue augmentation.mPEG-PDLLA micro-spheres were prepared by utilizing a SPG membrane emulsifier which endowed microspheres with good sphericity and particle size uniformity.PDLLA-PEG-PDLLA hydrogel which shared the same component with the mPEG-PDLLA copolymer acted as a carrier and fixed the microspheres at the injected sites.The mPEG-PDLLA microsphere/PDLLA-PEG-PDLLA hydrogel composite was flowable in room temperature and transformed into gel after being heated to body temperature.This feature is convenient for subcutaneous filling.In vivo assessment on mice showed good safety profile of the composite.Moreover,the density of collagen fibers increased over 13 weeks.Overall,this biocompatible microsphere/hydrogel composite involves simple component and no extra crosslinking agents,and has the ability to stimulate collagen production,thus,may be a candidate for soft tissue augmentation.展开更多
Multiple myeloma(MM)is the second most common hematological tumor characterized by the proliferation of monoclonal plasma cells.Melphalan(MEL)is commonly used in the treatment of MM and is especially essential for pat...Multiple myeloma(MM)is the second most common hematological tumor characterized by the proliferation of monoclonal plasma cells.Melphalan(MEL)is commonly used in the treatment of MM and is especially essential for patients undergoing autologous stem cell transplantation(ASCT).Although many drugs for MM have been developed in recent years,chemotherapy followed by ASCT remains the optimal option.Melphalan,the backbone of the conditioning regimen,brings severe toxicities at a high dose.Nanodrug delivery systems enable drugs to be highly effective and have low toxicity.In this study,methoxy poly(ethylene glycol)-poly(D,L-lactide)copolymer(MPEG-PDLLA)was chosen to encapsulate melphalan,and the characteristics,effectiveness,and safety of MEL/MPEG-PDLLA in vitro and in vivo were investigated.MEL/MPEG-PDLLA showed slow release and was easily engulfed by MM cells despite a result of the antitumor assay comparable to that of free melphalan in vitro.The in vivo results showed that MEL/MPEG-PDLLA could significantly alleviate tumor burden and prolong survival time without increasing the toxicity to vital organs.In addition,MEL/MPEG-PDLLA could significantly reduce the damage to the intestinal mucosa caused by melphalan.In conclusion,MEL/MPEG-PDLLA shows improved antitumor activity and has the potential to alleviate pains of MM patients undergoing ASCT.展开更多
文摘目的合成聚乙二醇单甲醚-聚乳酸(mPEG-PDLLA)嵌段共聚物,制备去氧鬼臼毒素mPEG-PDLLA嵌段共聚物(DPT-PM),提高去氧鬼臼毒素在水中的溶解度。方法以开环聚合反应合成mPEG-PDLLA,并通过IR、1H-HMR确证其结构,芘荧光探针法测定其临界胶束浓度(CMC);采用溶剂蒸发法制备DPT-PM溶液,并将其冷冻干燥;分别采用动态光散射法(DLS)、透射电子显微镜(TEM)、差示扫描量热法(DSC)、高效液相色谱法(HPLC)等手段对胶束形态、粒径与分布、载药量、包封率等进行表征,并采用透析法考察DPT-PM体外释放,并对释放机制进行探讨。结果制备了去氧鬼臼毒素共聚物胶束,透射电镜下观察为近球形,平均粒径为22.0±8.9nm,载药量为20.67%,包封率为99.63%。结论 m PEG-PDLLA聚合物胶束可作为疏水性药物去氧鬼臼毒素的载体,具有较高的载药性能,能一定程度提高去氧鬼臼毒素在水中的溶解度。
基金financially supported by National Natural Science Foundation of China(Nos.32171386 and 32201157)the Natural Science Foundation of Tianjin of China(No.21JCZDJC01250)the China Postdoctoral Science Foundation(No.2021M690793)。
文摘Engineering small-molecule drugs into nanoparticulate formulations provides an unprecedented opportunity to improve the performance of traditional chemo drugs,but suffers from poor compatibility between drugs and nanocarriers.Stimuli-responsive mPEG-PDLLA–drug conjugate-based nanomedicines can facilitate the exploitation of beneficial properties of the carrier and enable the practical fabrication of highly efficacious self-assembled nanomedicines.However,the influence of hydrophobic length on the performance of this type of nanomedicine is little known.Here we synthesized two acid-sensitive ketal-linked mPEG-PDLLA–docetaxel prodrugs with different lengths of PDLLA,and engineered them into self-assembled sub-20 nm micellar nanomedicines for breast cancer chemotherapy.We found that the nanomedicine consisting of a mPEG-PDLLA–docetaxel prodrug with the shorter length of PDLLA stood out due to its potent cytotoxicity,deep penetration into multicellular spheroids,and improved in vivo anticancer performance.Additionally,our prodrug-based nanomedicines outperformed the generic formulation of commercial Nanoxel in terms of safety profile,tolerated doses,and tumor suppression.Our findings indicate that the hydrophobic content of a polymeric prodrug nanomedicine plays an important role in the performance of the nanomedicine,and should be instructive for developing polymeric prodrug-based nanomedicines with clinical translational potential.
基金supported by the National Natural Science Foundation of China(Nos.NSFC31930067,NSFC31771096,and NSFC31525009)the National Key Research and Development Pro-gram of China(No.2017YFC1103502)the 1·3·5 Project for Disci-plines of Excellence,West China Hospital,Sichuan University(No.ZYGD18002)。
文摘Injectable filling material is a simple and efficient method for soft tissues reconstruction and is extremely popular in not only plastic surgery but also cosmetic industry.However,there is a lack of soft tissue fillers with perfect performance on the market currently.Here,we constructed a new microsphere/hydrogel composite and evaluated its potential as a candidate for soft tissue augmentation.mPEG-PDLLA micro-spheres were prepared by utilizing a SPG membrane emulsifier which endowed microspheres with good sphericity and particle size uniformity.PDLLA-PEG-PDLLA hydrogel which shared the same component with the mPEG-PDLLA copolymer acted as a carrier and fixed the microspheres at the injected sites.The mPEG-PDLLA microsphere/PDLLA-PEG-PDLLA hydrogel composite was flowable in room temperature and transformed into gel after being heated to body temperature.This feature is convenient for subcutaneous filling.In vivo assessment on mice showed good safety profile of the composite.Moreover,the density of collagen fibers increased over 13 weeks.Overall,this biocompatible microsphere/hydrogel composite involves simple component and no extra crosslinking agents,and has the ability to stimulate collagen production,thus,may be a candidate for soft tissue augmentation.
基金supported by the National Natural Science Foundation of China(Nos.U21A20417,31930067,32271450,31700868)PostDoc Research Project,West China Hospital,Sichuan University(No.2020HXBH165)1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYGD18002)。
文摘Multiple myeloma(MM)is the second most common hematological tumor characterized by the proliferation of monoclonal plasma cells.Melphalan(MEL)is commonly used in the treatment of MM and is especially essential for patients undergoing autologous stem cell transplantation(ASCT).Although many drugs for MM have been developed in recent years,chemotherapy followed by ASCT remains the optimal option.Melphalan,the backbone of the conditioning regimen,brings severe toxicities at a high dose.Nanodrug delivery systems enable drugs to be highly effective and have low toxicity.In this study,methoxy poly(ethylene glycol)-poly(D,L-lactide)copolymer(MPEG-PDLLA)was chosen to encapsulate melphalan,and the characteristics,effectiveness,and safety of MEL/MPEG-PDLLA in vitro and in vivo were investigated.MEL/MPEG-PDLLA showed slow release and was easily engulfed by MM cells despite a result of the antitumor assay comparable to that of free melphalan in vitro.The in vivo results showed that MEL/MPEG-PDLLA could significantly alleviate tumor burden and prolong survival time without increasing the toxicity to vital organs.In addition,MEL/MPEG-PDLLA could significantly reduce the damage to the intestinal mucosa caused by melphalan.In conclusion,MEL/MPEG-PDLLA shows improved antitumor activity and has the potential to alleviate pains of MM patients undergoing ASCT.
