Size is one of the most important characteristics of nanoparticles to influence their biodistribution and antitumoral efficacy.Particles with large sizes have difficulty in deep tumor penetration,while small particles...Size is one of the most important characteristics of nanoparticles to influence their biodistribution and antitumoral efficacy.Particles with large sizes have difficulty in deep tumor penetration,while small particles are easily removed from tumor tissues due to the high tumor interstitial fluid pressure.To address these issues,an intelligent core-crosslinked polyion complex micelle(cPCM)with a reversibly sizeswitchable feature was engineered in this study.The micelles are consisting of methoxy poly(ethylene glycol)-poly(D,L-lactide)copolymer(mPEG-PLA),mPEG-PLA-(HE)6CC,and mPEG-PLA-(RG)6CC at an optimal mass ratio of 6:1:1 with an antiangiogenic compound,dabigatran etexilate(DE),encapsulated.The net charge inside the micelles is switchable when exposed to different pH conditions,thereby leading to revisable size-change of micelles.DE-loaded micelles(DE@cPCM)can swell and release drugs at the tumor sites with a mildly acidic pH,while they shrink and protect the cargo from leaking into the blood circulation with a neutral pH.Results indicated that DE@cPCM can inhibit tumor angiogenesis in vitro and in vivo,thereby efficiently restraining tumor growth in a 4T1-bearing mouse model.Collectively,the sizeswitchable cPCM is a promising nanoplatform for targeting delivery of anticarcinogens into the matrix of tumor tissues.展开更多
A rotundine-polyion complex(PIC)release system was prepared first by granulation of rotundine containing chitosan acetate solution and then by complexing with carboxymethyl glucomannan(CMGM)solution on the granular su...A rotundine-polyion complex(PIC)release system was prepared first by granulation of rotundine containing chitosan acetate solution and then by complexing with carboxymethyl glucomannan(CMGM)solution on the granular surface.The granules have an average diameter of 1.38-1.53 mm and the drug content reaches 62.89％.The external release tests showed T_(50) to be 45 rain and the total release time 4 h in an artificial gastric juice,while no more than 60％ of the drug was released in the same period of time in an ar- tificial intestinal fluid.The various factors affecting the external release were examined.展开更多
Polyion complex （PIC） micelles were spontaneously formed in aqueous solutions through electrostatic interaction between two oppositely charged block copolymers, poly（N-isopropylacrylamide）-b-poly（L-glutamic acid...Polyion complex （PIC） micelles were spontaneously formed in aqueous solutions through electrostatic interaction between two oppositely charged block copolymers, poly（N-isopropylacrylamide）-b-poly（L-glutamic acid） and poly（N-isopropylacrylamide）-b-poly（L-lysine）. Their controlled synthesis was achieved via the ring opening polymerization of N-carboxyanhydrides （NCA）, ε-benzyloxycarbonyl-L-lysine （Lys（Z）-NCA） or γ-benzyl-L-glutamate （BLG-NCA） with amino-terminated poly（N-isopropylacrylamide） macroinitiator and the subsequent deprotection reaction. The formation of PIC micelles was confirmed by dynamic light scattering and transmission electron microscopy. Turbidimetric characterization suggested that the formed PIC micelles had a concentration-dependent thermosensitivity and their phase transition behaviors could be easily adjusted either by the block length of coplymers or the concentration of micelles.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81972894,22278442,82273882)。
文摘Size is one of the most important characteristics of nanoparticles to influence their biodistribution and antitumoral efficacy.Particles with large sizes have difficulty in deep tumor penetration,while small particles are easily removed from tumor tissues due to the high tumor interstitial fluid pressure.To address these issues,an intelligent core-crosslinked polyion complex micelle(cPCM)with a reversibly sizeswitchable feature was engineered in this study.The micelles are consisting of methoxy poly(ethylene glycol)-poly(D,L-lactide)copolymer(mPEG-PLA),mPEG-PLA-(HE)6CC,and mPEG-PLA-(RG)6CC at an optimal mass ratio of 6:1:1 with an antiangiogenic compound,dabigatran etexilate(DE),encapsulated.The net charge inside the micelles is switchable when exposed to different pH conditions,thereby leading to revisable size-change of micelles.DE-loaded micelles(DE@cPCM)can swell and release drugs at the tumor sites with a mildly acidic pH,while they shrink and protect the cargo from leaking into the blood circulation with a neutral pH.Results indicated that DE@cPCM can inhibit tumor angiogenesis in vitro and in vivo,thereby efficiently restraining tumor growth in a 4T1-bearing mouse model.Collectively,the sizeswitchable cPCM is a promising nanoplatform for targeting delivery of anticarcinogens into the matrix of tumor tissues.
基金This project was supported by National Natural Science Foundation of China
文摘A rotundine-polyion complex(PIC)release system was prepared first by granulation of rotundine containing chitosan acetate solution and then by complexing with carboxymethyl glucomannan(CMGM)solution on the granular surface.The granules have an average diameter of 1.38-1.53 mm and the drug content reaches 62.89％.The external release tests showed T_(50) to be 45 rain and the total release time 4 h in an artificial gastric juice,while no more than 60％ of the drug was released in the same period of time in an ar- tificial intestinal fluid.The various factors affecting the external release were examined.
基金financially supported by the National Natural Science Foundation of China (Nos. 20904053, 51021003,51173184)the Ministry of Science and Technology of China (International cooperation program 2011RI0001)the Program of the Science and Technology of Changchun (No. 2010061)
文摘Polyion complex （PIC） micelles were spontaneously formed in aqueous solutions through electrostatic interaction between two oppositely charged block copolymers, poly（N-isopropylacrylamide）-b-poly（L-glutamic acid） and poly（N-isopropylacrylamide）-b-poly（L-lysine）. Their controlled synthesis was achieved via the ring opening polymerization of N-carboxyanhydrides （NCA）, ε-benzyloxycarbonyl-L-lysine （Lys（Z）-NCA） or γ-benzyl-L-glutamate （BLG-NCA） with amino-terminated poly（N-isopropylacrylamide） macroinitiator and the subsequent deprotection reaction. The formation of PIC micelles was confirmed by dynamic light scattering and transmission electron microscopy. Turbidimetric characterization suggested that the formed PIC micelles had a concentration-dependent thermosensitivity and their phase transition behaviors could be easily adjusted either by the block length of coplymers or the concentration of micelles.
