In recent years, organic-inorganic hybrid nanocarriers are explored for effective drug delivery and preferable disease treatments. In this study, using 5-fluorouracil(5-FU)as electronegative model drug, a new type of ...In recent years, organic-inorganic hybrid nanocarriers are explored for effective drug delivery and preferable disease treatments. In this study, using 5-fluorouracil(5-FU)as electronegative model drug, a new type of organic-inorganic hybrid drug delivery system(LDH/HA-PEG/5-FU)was conceived and manufactured by the adsorption of PEGylated hyaluronic acid(HA-PEG)on the surface of layered double hydroxide(LDH, prepared via hydrothermal method)and the intercalation of 5-FU in the interlamination of LDH via ion exchange strategy. The drug loading amount of LDH/HA-PEG/5-FU achieved as high as 34.2%. LDH, LDH/5-FU and LDH/HA-PEG/5-FU were characterized by FT-IR, XRD, TGA, laser particle size analyzer and SEM. With the benefit of p Hdegradable feature of LDH and enzyme-degradable feature of HA, LDH/HA-PEG/5-FU showed p H-degradable and enzyme-degradable capacity in in vitro drug release. Moreover, the drug carrier LDH/HA-PEG contained biocompatible PEG and tumor-targeted HA, resulting in lower cytotoxicity and better endocytosis compared with LDH in vitro. It was suggested that the organic-inorganic hybrid drug delivery system, which was endowed with the properties of controlled release, low toxicity and tumor-targeting delivery for ameliorative cancer therapy, was advisable and might be applied further to fulfill other treatments.展开更多
To reduce the problems of poor solubility,high in vivo dosage requirement,and weak targeting ability of paclitaxel(PTX),a hyaluronic acid-octadecylamine(HA-ODA)-modified nano-structured lipid carrier(HA-NLC)was constr...To reduce the problems of poor solubility,high in vivo dosage requirement,and weak targeting ability of paclitaxel(PTX),a hyaluronic acid-octadecylamine(HA-ODA)-modified nano-structured lipid carrier(HA-NLC)was constructed.HA-ODA conjugates were synthesized by an amide reaction between HA and ODA.The hydrophobic chain of HA-ODA can be embedded in the lipid core of the NLC to obtain HA-NLC.The HA-NLC displayed strong internalization in cluster determinant 44(CD44)highly expressed MCF-7 cells,and endocytosis mediated by the CD44 receptor was involved.The HA-NLC had an encapsulation efficiency of PTX of 72.0%.The cytotoxicity of the PTXloaded nanoparticle HA-NLC/PTX in MCF-7 cells was much stronger than that of the commercial preparation Taxol.In vivo,the HA-NLC exhibited strong tumor targeting ability.The distribution of the NLCs to the liver and spleen was reduced after HA modification,while more nanoparticles were aggregated to the tumor site.Our results suggest that HA-NLC has excellent properties as a nano drug carrier and potential for in vivo targeting.展开更多
基金Supported by the National Natural Science Foundation of China(No.81371667,No.31271073)
文摘In recent years, organic-inorganic hybrid nanocarriers are explored for effective drug delivery and preferable disease treatments. In this study, using 5-fluorouracil(5-FU)as electronegative model drug, a new type of organic-inorganic hybrid drug delivery system(LDH/HA-PEG/5-FU)was conceived and manufactured by the adsorption of PEGylated hyaluronic acid(HA-PEG)on the surface of layered double hydroxide(LDH, prepared via hydrothermal method)and the intercalation of 5-FU in the interlamination of LDH via ion exchange strategy. The drug loading amount of LDH/HA-PEG/5-FU achieved as high as 34.2%. LDH, LDH/5-FU and LDH/HA-PEG/5-FU were characterized by FT-IR, XRD, TGA, laser particle size analyzer and SEM. With the benefit of p Hdegradable feature of LDH and enzyme-degradable feature of HA, LDH/HA-PEG/5-FU showed p H-degradable and enzyme-degradable capacity in in vitro drug release. Moreover, the drug carrier LDH/HA-PEG contained biocompatible PEG and tumor-targeted HA, resulting in lower cytotoxicity and better endocytosis compared with LDH in vitro. It was suggested that the organic-inorganic hybrid drug delivery system, which was endowed with the properties of controlled release, low toxicity and tumor-targeting delivery for ameliorative cancer therapy, was advisable and might be applied further to fulfill other treatments.
基金Project supported by the Zhejiang Provincial Natural Science Foundation of China(No.LY14H160016)。
文摘To reduce the problems of poor solubility,high in vivo dosage requirement,and weak targeting ability of paclitaxel(PTX),a hyaluronic acid-octadecylamine(HA-ODA)-modified nano-structured lipid carrier(HA-NLC)was constructed.HA-ODA conjugates were synthesized by an amide reaction between HA and ODA.The hydrophobic chain of HA-ODA can be embedded in the lipid core of the NLC to obtain HA-NLC.The HA-NLC displayed strong internalization in cluster determinant 44(CD44)highly expressed MCF-7 cells,and endocytosis mediated by the CD44 receptor was involved.The HA-NLC had an encapsulation efficiency of PTX of 72.0%.The cytotoxicity of the PTXloaded nanoparticle HA-NLC/PTX in MCF-7 cells was much stronger than that of the commercial preparation Taxol.In vivo,the HA-NLC exhibited strong tumor targeting ability.The distribution of the NLCs to the liver and spleen was reduced after HA modification,while more nanoparticles were aggregated to the tumor site.Our results suggest that HA-NLC has excellent properties as a nano drug carrier and potential for in vivo targeting.
