目的:探讨负载奥沙利铂的聚乳酸-乙醇酸共聚物(PLGA)微粒大鼠体内外生物安全性,验证负载奥沙利铂的PLGA微粒的注射可行性。方法:采用细胞增殖实验法CCK-8检测微粒对小鼠上皮样成纤维细胞L929增殖速率的影响,评估其体外安全性。将微球注...目的:探讨负载奥沙利铂的聚乳酸-乙醇酸共聚物(PLGA)微粒大鼠体内外生物安全性,验证负载奥沙利铂的PLGA微粒的注射可行性。方法:采用细胞增殖实验法CCK-8检测微粒对小鼠上皮样成纤维细胞L929增殖速率的影响,评估其体外安全性。将微球注射于200~250 g SD雌性大鼠右侧小腿后侧肌肉,检测血常规(WBC、HGB、PLT、PCT)及血生化指标(ALT、AST、TP、ALB、ALP、BUN、Cre、CHO、TBIL)。主要器官(肝脏、肾脏、骨髓、肌肉)的病理切片进行H&E染色,验证纳米颗粒体内的生物安全性。结果:体外细胞增殖实验显示负载奥沙利铂的PLGA药物因缓释奥沙利铂功能可能表现出一定的细胞毒性,体内实验未表现出明显慢性毒性,病理组织切片H&E染色未提示重要组织慢性损伤。结论:负载奥沙利铂的PLGA微粒符合可注射要求,不会对注射部位造成损伤,注射后未引起明显急、慢性副作用,具有较高的安全性,有望应用于临床治疗胃癌提供新方法。展开更多
Herein,porous poly(lactic-co-glycolic acid)(PLGA)microspheres were prepared to load icariin andmiR-23b for the treatment of metastatic lung cancer.The microspheres exhibited desirable aerodynamic diameter,high drug lo...Herein,porous poly(lactic-co-glycolic acid)(PLGA)microspheres were prepared to load icariin andmiR-23b for the treatment of metastatic lung cancer.The microspheres exhibited desirable aerodynamic diameter,high drug loading and encapsulation efficiency,as well as a favorable drug release profile,which was beneficial for the deposition and exposure of drugs in the lung tissues.The release solution from microspheres exhibited a favorable anti-proliferative effect by inducting cell apoptosis and arresting the cell cycle at G1 phase,and meanwhile inhibited the migration and invasion of cancer cells.More importantly,the microspheres could be effectively inhaled and accumulated in the lung tissues to trigger the in situ apoptosis of tumor cells and suppress metastasis,using mice bearing melanoma-metastatic lung cancer as a model.Furthermore,inhalation of themicrospheres showed favorable biocompatibility,barely causing tissue damage.Overall,porous PLGA microspheres provide a promising platform for the inhalable co-delivery of drugs and genes to obtain ideal therapeutic efficacy in lung cancer and other pulmonary diseases.展开更多
ObjectiveTo develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).MethodsDEX microcrystals(MCs)were prepared via precipitation,while LA-loaded porous P...ObjectiveTo develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).MethodsDEX microcrystals(MCs)were prepared via precipitation,while LA-loaded porous PLGA microspheres(LPMPs)were fabricated using a double emulsion–solvent evaporation method.DEX MCs were physically perfused into LPMPs via negative pressure to form a combined system(DEX MCs+LPMPs).Physicochemical properties,in vitro drug release,pharmacokinetics,and biocompatibility were evaluated.Guinea pigs were used for intratympanic injections of DEX MCs,LPMPs,or DEX MCs+LPMPs.ResultsThe DEX MCs+LPMPs system enabled simultaneous release of both drugs,with DEX exhibiting superior pharmacokinetics(sustained perilymph concentrations up to 7 days)compared to DEX MCs alone.LA release from LPMPs demonstrated prolonged kinetics without burst release.SEM confirmed DEX MCs were localized within/on LPMPs and adhered to the round window membrane(RWM).Histological analysis revealed normal cochlear morphology and no inflammatory response,confirming biocompatibility.ConclusionsThis novel codelivery system combining microcrystals and porous microspheres achieves sustained dual-drug release,enhances therapeutic efficacy,and offers a promising strategy for managing hearing loss via intratympanic administration.展开更多
文摘目的:探讨负载奥沙利铂的聚乳酸-乙醇酸共聚物(PLGA)微粒大鼠体内外生物安全性,验证负载奥沙利铂的PLGA微粒的注射可行性。方法:采用细胞增殖实验法CCK-8检测微粒对小鼠上皮样成纤维细胞L929增殖速率的影响,评估其体外安全性。将微球注射于200~250 g SD雌性大鼠右侧小腿后侧肌肉,检测血常规(WBC、HGB、PLT、PCT)及血生化指标(ALT、AST、TP、ALB、ALP、BUN、Cre、CHO、TBIL)。主要器官(肝脏、肾脏、骨髓、肌肉)的病理切片进行H&E染色,验证纳米颗粒体内的生物安全性。结果:体外细胞增殖实验显示负载奥沙利铂的PLGA药物因缓释奥沙利铂功能可能表现出一定的细胞毒性,体内实验未表现出明显慢性毒性,病理组织切片H&E染色未提示重要组织慢性损伤。结论:负载奥沙利铂的PLGA微粒符合可注射要求,不会对注射部位造成损伤,注射后未引起明显急、慢性副作用,具有较高的安全性,有望应用于临床治疗胃癌提供新方法。
基金the National Natural Science Foundation of China(32271319 and 32071267)the Science and Technology Department of Jilin Province(YDZJ202301ZYTS537 and 20240402035GH)+1 种基金the Development and Reform Commission of Jilin Province(2023C015)the“Medicine+X”cross-innovation team of Bethune Medical Department of Jilin University“Leading the Charge with Open Competition”construction project(2022JBGS04).
文摘Herein,porous poly(lactic-co-glycolic acid)(PLGA)microspheres were prepared to load icariin andmiR-23b for the treatment of metastatic lung cancer.The microspheres exhibited desirable aerodynamic diameter,high drug loading and encapsulation efficiency,as well as a favorable drug release profile,which was beneficial for the deposition and exposure of drugs in the lung tissues.The release solution from microspheres exhibited a favorable anti-proliferative effect by inducting cell apoptosis and arresting the cell cycle at G1 phase,and meanwhile inhibited the migration and invasion of cancer cells.More importantly,the microspheres could be effectively inhaled and accumulated in the lung tissues to trigger the in situ apoptosis of tumor cells and suppress metastasis,using mice bearing melanoma-metastatic lung cancer as a model.Furthermore,inhalation of themicrospheres showed favorable biocompatibility,barely causing tissue damage.Overall,porous PLGA microspheres provide a promising platform for the inhalable co-delivery of drugs and genes to obtain ideal therapeutic efficacy in lung cancer and other pulmonary diseases.
基金supported by Capital’s Funds for Health Improvement and Research(CFH:2022-2-5072)the Tianjin Natural Science Foundation for Jingjinji Collaboration(23JCZXJC00240)+1 种基金Beijing Natural Science Foundation(J230006)the CAMS Innovation Fund for Medical Science(2021-I2M-1-052).
文摘ObjectiveTo develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).MethodsDEX microcrystals(MCs)were prepared via precipitation,while LA-loaded porous PLGA microspheres(LPMPs)were fabricated using a double emulsion–solvent evaporation method.DEX MCs were physically perfused into LPMPs via negative pressure to form a combined system(DEX MCs+LPMPs).Physicochemical properties,in vitro drug release,pharmacokinetics,and biocompatibility were evaluated.Guinea pigs were used for intratympanic injections of DEX MCs,LPMPs,or DEX MCs+LPMPs.ResultsThe DEX MCs+LPMPs system enabled simultaneous release of both drugs,with DEX exhibiting superior pharmacokinetics(sustained perilymph concentrations up to 7 days)compared to DEX MCs alone.LA release from LPMPs demonstrated prolonged kinetics without burst release.SEM confirmed DEX MCs were localized within/on LPMPs and adhered to the round window membrane(RWM).Histological analysis revealed normal cochlear morphology and no inflammatory response,confirming biocompatibility.ConclusionsThis novel codelivery system combining microcrystals and porous microspheres achieves sustained dual-drug release,enhances therapeutic efficacy,and offers a promising strategy for managing hearing loss via intratympanic administration.
