In this study, a p H-sensitive micelle self-assembled from poly(L-histidine) based triblock copolymers of poly(ethylene glycol)–poly(D,L-lactide)–poly(L-histidine)(mPEG-PLA-PHis) was prepared and used as the intrace...In this study, a p H-sensitive micelle self-assembled from poly(L-histidine) based triblock copolymers of poly(ethylene glycol)–poly(D,L-lactide)–poly(L-histidine)(mPEG-PLA-PHis) was prepared and used as the intracellular doxorubicin(Dox) delivery for cancer chemotherapy. Dox was loaded into the micelles by thin-film hydration method and a Box–Behnken design for three factors at three levels was used to optimize the preparations. The optimized mPEG-PLA-Phis/Dox micelles exhibited good encapsulation efficiency of 91.12%,a mean diameter of 45 nm and narrow size distribution with polydispersity index of 0.256.In vitro drug release studies demonstrated that Dox was released from the micelles in a p Hdependent manner. Furthermore, the cellular evaluation of Dox loaded micelles displayed that the micelles possessed high antitumor activity in vitro with an IC50 of 35.30 μg/ml against MCF-7/ADR cells. The confocal microscopy and flow cytometry experiments indicated that m PEG-PLA-Phis micelles mediated efficient cytoplasmic delivery of Dox with the aid of poly(Lhistidine) mediated endosomal escape. In addition, blank m PEG-PLA-Phis micelles were shown to be nontoxic to MCF-7/ADR cells even at a high concentration of 200 μg/ml. The pHsensitive mPEG-PLA-PHis micelles have been demonstrated to be a promising nanosystem for the intracellular delivery of Dox for MDR reversal.展开更多
In order to enhance the efficiency and specificity of anticancer drug delivery and realize intelligently controlled release,a new multi-functional nanoparticle drug carrier was synthesized.The drug carrier was prepare...In order to enhance the efficiency and specificity of anticancer drug delivery and realize intelligently controlled release,a new multi-functional nanoparticle drug carrier was synthesized.The drug carrier was prepared by functionalizing multi-walled carbon nanotubes(MWCNTs) with polyethylenimines(PEI),fluorescein isothiocyanate(FITC) and glycyrrhizic acid(GL).After detailed characterization,doxorubicin(DOX) was loaded onto the obtained MWCNT composites through π-π stacking interactions.The drug loading capacity of the GL-functionalized material was up to 92%,and the release behavior was significantly pH-sensitive.Release at pH = 5.8(typical of the tumor cell microenvironment) was much more rapid and reached a greater extent than release under normal physiological conditions(pH = 7.4).The modified MWCNTs had high biocompatibility with the liver cancer cell line SMMC-7721,but were able to induce cell death after 24 h incubation if loaded with DOX.Tests with shorter incubation time(2 h) were undertaken to investigate the selectivity of the MWCNT composites,showed that the nanocomposites could specifically target cancer cells.The above results suggest that the functionalized carbon nanotubes-based material has potential applications for targeted delivery and controlled release of anticancer drug.展开更多
The protectivity of the natural honey has been assessed against the toxicity of Doxorubicin (DOX) in liver tissues of 106 male Albino mice Mus musculus strain weighing 37 ± 3 gm. The body and liver weights, morph...The protectivity of the natural honey has been assessed against the toxicity of Doxorubicin (DOX) in liver tissues of 106 male Albino mice Mus musculus strain weighing 37 ± 3 gm. The body and liver weights, morphological behavior changes, liver function and pathological effects on liver were recorded. Toxicity study of DOX showed that the LD50 and LD were 20 and 30 mg/Kg, respectively. Intra-peritoneal (i.p.) injection of DOX induced significant (p ≤ 0.01-0.001) pathological changes in the health, i.e. general weakness, a few morphological changes associated with bleedings, ulceration of skin, hair loss, dimorphism of limbs and bosselation. Daily ingestion of natural honey for seven weeks has led to significant (p ≤ 0.01-0.001) improvement of these symptoms which appeared as increases in both body and liver weights in comparison with control animals. The natural honey had enhanced the function of liver in treated animals with DOX + honey and reduced the pathological effects of DOX on the above morphological symptoms as well as in the hepatocytes. It is concluded that the ingestion of natural honey has a protective potency against the toxic effects of DOX.展开更多
文摘In this study, a p H-sensitive micelle self-assembled from poly(L-histidine) based triblock copolymers of poly(ethylene glycol)–poly(D,L-lactide)–poly(L-histidine)(mPEG-PLA-PHis) was prepared and used as the intracellular doxorubicin(Dox) delivery for cancer chemotherapy. Dox was loaded into the micelles by thin-film hydration method and a Box–Behnken design for three factors at three levels was used to optimize the preparations. The optimized mPEG-PLA-Phis/Dox micelles exhibited good encapsulation efficiency of 91.12%,a mean diameter of 45 nm and narrow size distribution with polydispersity index of 0.256.In vitro drug release studies demonstrated that Dox was released from the micelles in a p Hdependent manner. Furthermore, the cellular evaluation of Dox loaded micelles displayed that the micelles possessed high antitumor activity in vitro with an IC50 of 35.30 μg/ml against MCF-7/ADR cells. The confocal microscopy and flow cytometry experiments indicated that m PEG-PLA-Phis micelles mediated efficient cytoplasmic delivery of Dox with the aid of poly(Lhistidine) mediated endosomal escape. In addition, blank m PEG-PLA-Phis micelles were shown to be nontoxic to MCF-7/ADR cells even at a high concentration of 200 μg/ml. The pHsensitive mPEG-PLA-PHis micelles have been demonstrated to be a promising nanosystem for the intracellular delivery of Dox for MDR reversal.
基金Science and Technology Commission of Shanghai Municipality,China(No.16410723700)"111 Project" Biomedical Textile Materials Science and Technology,China(No.B07024)the UK-China Joint Laboratory for Therapeutic Textiles
文摘In order to enhance the efficiency and specificity of anticancer drug delivery and realize intelligently controlled release,a new multi-functional nanoparticle drug carrier was synthesized.The drug carrier was prepared by functionalizing multi-walled carbon nanotubes(MWCNTs) with polyethylenimines(PEI),fluorescein isothiocyanate(FITC) and glycyrrhizic acid(GL).After detailed characterization,doxorubicin(DOX) was loaded onto the obtained MWCNT composites through π-π stacking interactions.The drug loading capacity of the GL-functionalized material was up to 92%,and the release behavior was significantly pH-sensitive.Release at pH = 5.8(typical of the tumor cell microenvironment) was much more rapid and reached a greater extent than release under normal physiological conditions(pH = 7.4).The modified MWCNTs had high biocompatibility with the liver cancer cell line SMMC-7721,but were able to induce cell death after 24 h incubation if loaded with DOX.Tests with shorter incubation time(2 h) were undertaken to investigate the selectivity of the MWCNT composites,showed that the nanocomposites could specifically target cancer cells.The above results suggest that the functionalized carbon nanotubes-based material has potential applications for targeted delivery and controlled release of anticancer drug.
文摘The protectivity of the natural honey has been assessed against the toxicity of Doxorubicin (DOX) in liver tissues of 106 male Albino mice Mus musculus strain weighing 37 ± 3 gm. The body and liver weights, morphological behavior changes, liver function and pathological effects on liver were recorded. Toxicity study of DOX showed that the LD50 and LD were 20 and 30 mg/Kg, respectively. Intra-peritoneal (i.p.) injection of DOX induced significant (p ≤ 0.01-0.001) pathological changes in the health, i.e. general weakness, a few morphological changes associated with bleedings, ulceration of skin, hair loss, dimorphism of limbs and bosselation. Daily ingestion of natural honey for seven weeks has led to significant (p ≤ 0.01-0.001) improvement of these symptoms which appeared as increases in both body and liver weights in comparison with control animals. The natural honey had enhanced the function of liver in treated animals with DOX + honey and reduced the pathological effects of DOX on the above morphological symptoms as well as in the hepatocytes. It is concluded that the ingestion of natural honey has a protective potency against the toxic effects of DOX.
