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Preparation and Characterization of polymeric micelles from Poly (D, L-lactide) and Methoxypolyethylene Glycol Block Copolymers as Potential Drug Carriers

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Tsinghua Science and Technology 2007年第4期12卷 493-496页

作者：张建峥姜维赵秀文王运东 State Key Laboratory of Chemical Engineering Department of Chemical Engineering Tsinghua University

Amphiphilic diblock copolymers composed of methoxy polyethylene glycol （MePEG） and poly（D,L-lactide）（PDLLA） were prepared for the preparation of polymeric micelles, The use of MePEG-PDLLA as drug carriers has been reported in the open literature, but there are only few data on the application of a series of MePEG-PDLLA copolymers with different lengths in the medical field, The shape of the polymeric micelles is also important in drug delivery, Studies on in vitro drug release profiles require a good sink condition. The critical micelle concentration of a series of MePEG-PDLLA has a significant role in drug release. To estimate their feasibility as a drug carrier, polymeric micelles made of MePEG-PDLLA block copolymer were prepared by the oil in water （O/VV） emulsion method. From dynamic light scattering （DLS） measurements, the size of the micelle formed was less than 200 nm, The critical micelle concentration of polymeric micelles with various compositions was determined using pyrene as a fluorescence probe. The critical micelle concentration decreased with increasing number of hydrophobic segments. MePEG-PDLLA micelles have a considerably low critical micelle concentration （0.4～0.5 μg/mL）, which is apparently an advantage in utilizing these micelles as drug carriers. The morphology of the polymeric micelles was observed using scanning electron microscopy （SEM） and transmission electron microscopy （TEM）, The micelles were found to be nearly spherical. The yield of the polymeric micelles obtained from the O/W method is as high as 85%.

关键词： poly(D,L-lactide) methoxy polyethylene glycol polymeric micelle drug carrier

ROS-removing nano-medicine for navigating inflammatory microenvironment to enhance anti-epileptic therapy

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Acta Pharmaceutica Sinica B 2023年第3期13卷 1246-1261页

作者： Zheng Zhou Keying Li Yongchao Chu Chao Li Tongyu Zhang Peixin Liu Tao Sun Chen Jiang Department of Pharmaceutics School of PharmacyFudan University、Key Laboratory of Smart Drug DeliveryMinistry of Education、State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceShanghai 201203China

As a neurological disorder in the brain,epilepsy is not only associated with abnormal synchronized discharging of neurons,but also inseparable from non-neuronal elements in the altered ***-epileptic drugs(AEDs)merely focusing on neuronal circuits frequently turn out deficient,which is necessitating comprehensive strategies of medications to cover over-exciting neurons,activated glial cells,oxidative stress and chronic inflammation ***,we would report the design of a polymeric micelle drug delivery system that was functioned with brain targeting and cerebral microenvironment *** brief,reactive oxygen species(ROS)-sensitive phenylboronic ester was conjugated with poly-ethylene glycol(PEG)to form amphiphilic ***,dehydroascorbic acid(DHAA),an analogue of glucose,was applied to target glucose transporter 1(GLUT1)and facilitate micelle penetration across the blood‒brain barrier(BBB).A classic hydrophobic AED,lamotrigine(LTG),was encapsulated in the micelles via *** administrated and transferred across the BBB,ROS-scavenging polymers were expected to integrate anti-oxidation,anti-inflammation and neuro-electric modulation into one ***,micelles would alter LTG distribution in vivo with improved ***,the combined anti-epileptic therapy might provide effective opinions on how to maximize neuroprotection during early epileptogenesis.

关键词： Epilepsy polymeric micelle Reactive oxygen species Inflammation Gliosis Neuroprotection

Enhanced bioavailability and biosafety of cannabidiol nanomicelles for effective anti-inflammatory therapy

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Particuology 2022年第10期20卷 1-9页

作者： Yuan Rao Runwei Li Saixing Liu Linchao Meng Qilin Wu Qipeng Yuan Hao Liang Meng Qin College of Life Science and Technology Beijing University of Chemical TechnologyBeijing 100029China StarHealth Botanical Technology Corporation Beijing 100005China

Cannabidiol(CBD)shows great anti-inflammatory potential;however,the hydrophobicity and strong first-pass effect of CBD leads to its extremely low oral *** 407(P407)is a tri-block copolymer composed of(poly)ethylene oxide(PEO)and(poly)propylene oxide(PPO)*** has a PEO-PPO-PEO structure,which is widely used in the preparation of drug delivery systems that are highly *** it reaches a certain concentration in water,P407 can self-assemble into a micelle structure containing a hydrophobic core and a hydrophilic shell.A potential approach to enhanc-ing the oral bioavailability of hydrophobic drugs incorporating them into the hydrophilic *** prepared CBD nanomicelles with a drug loading of 14.29%by a cosolvent evaporation method using P407 with appropriate *** experiments indicated that anti-inflammatory markers(IL-4 and IL-10)increased,while inflammatory markers(TNF-αand IL-6)***,animal experiments showed that inflammatory cells were inhibited by CBD nanomicelles,and the anti-inflammatory effect of micelles was better than that of CBD,while no obvious evidence indicated toxicity to the liver and kidney.

关键词： CBD Poloxamer 407 polymeric micelle Anti-inflammatory Cytotoxicity

FOLATE-TARGETED OPTICAL AND MAGNETIC RESONANCE DUAL-MODALITY PCL-b-PEG micelleS FOR TUMOR IMAGING

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Chinese Journal of Polymer Science 2011年第4期29卷 427-430页

作者：唐建斌 Center for Bionanoengineering and the State Key Laboratory for Chemical Engineering Department of Chemical and Biological EngineeringZhejiang University

A biodegradable tumor targeting nano-probe based on poly（ε-caprolactone）-b-poly（ethylene glycol） block copolymer （PCL-b-PEG）micelle functionalized with a magnetic resonance imaging （MRI） contrast agent diethylenetriaminepentaacetic acid-gadolinium （DTPA-Gd＋） on the shell and a near-infrared （NIR） dye in the core for magnetic resonance and optical dual-modality imaging was prepared. The longitudinal relaxivity （rl） of the PCL-b-PEG- DTPA-Gd3＋ micelle was 13.4 （mmol/L）^-1s^-1, three folds of that of DTPA-Gd3＋, and higher than that of many polymeric contrast agents with similar structures. The in vivo optical imaging of a nude mouse bearing xenografied breast tumor showed that the dual-modality micelle preferentially accumulated in the tumor via the folic acid-mediated active targeting and the passive accumulation by the enhanced permeability and retention （EPR） effect. The results indicated that the dualmodality micelle is a promising nano-probe for cancer detection and diagnosis.

关键词： Dual-modality polymeric micelle MRI contrast agent Fluorescence Tumor imaging.

PEG-g-poly(aspartamide-co-N,N-dimethylethylenediamino aspartamide):Synthesis,characterization and its application as a drug delivery system

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Progress in Natural Science:Materials International 2009年第10期19卷 1305-1310页

作者： Dong Yang,Xiaohong Zhang,Li Yuan,Jianhua Hu Key Laboratory of Molecular Engineering of Polymers(Ministry of Education),Laboratory of Advanced Materials,Department of Macromolecular Science,Fudan University,Shanghai 200433,China Key Laboratory of Molecular Engineering of Polymers (Ministry of Education) Laboratory of Advanced Materials Department of Macromolecular Science Fudan University Shanghai 200433 China

PEG-g-poly(aspartamide-co-N,N-dimethylethylenediamino aspartamide)(PEG-DMEDA-PASP) was synthesized by two-step ring-opening reactions of polysuccinimide(PSI) with a-methoxy-x-amino-poly(ethylene glycol) and N,*** polymer structure was confirmed by 1H NMR and *** resultant PEG-DMEDA-PASP with ammonium glycyrrhizinate(AMG) could form polymeric micelles in aqueous *** results of transmission electron microscopy(TEM) and dynamic light scattering(DLS) measurements revealed that these polymeric micelles were spherical particles with a narrow diameter distribution and that their average diameter was ca.70 *** polymeric micelles had high-loading capacity(58%) and encapsulation efficiency(70%) for *** results of in vitro release experiments showed that these polymeric micelles possessed sustained-release effects,with a release rate of 25% within 3 h and 90% within 24 h.

关键词： PEG-g-poly(aspartamide-co-N,N-dimethylethylenediamino aspartamide) polymeric micelle Drug delivery system Ammonium glycyrrhizinate

Amphiphilic Block Copolymer micelles for Gene Delivery

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Chemical Research in Chinese Universities 2022年第6期38卷 1368-1379页

作者： LI Qin JIN Bixin LUO Yunjun LI Xiaoyu School of Material Science and Engineering Beijing Institute of TechnologyBeijing100081P.R.China Key Laboratory of High Energy Density Materials Ministry of EducationBeijing Institute of TechnologyBeijing100081P.R.China Experimental Centre of Advanced Materials Beijing Institute of TechnologyBeijing100081P.R.China

Gene therapy is a promising method to treat acquired and inherited diseases by introducing exogenous genes into specific recipient *** micelles with different nanoscopic morphologies and properties hold great promise for gene delivery *** cationic polymers,poly(ethyleneimine)(PEI),poly(L-lysine)(PLL),poly(2-dimethylaminoethyl methacrylate)(PDMAEMA)and novel cationic polymers poly(2-oxazoline)s(POxs),have been incorporated into block copolymers and decorated with targeting moieties to enhance transfection *** order to minimize cytotoxicity,nonionic block copolymer micelles are utilized to load gene through hydrophilic and hydrophobic interactions or covalent conjugations,*** our perspective,properties(shape,size,and mechanical stiffness,etc.)of block copolymer micelles may significantly affect cytotoxicity,transfection efficiency,circulation time,and load capacity of gene vectors in vivo and in *** review briefly sums up recent efforts in cationic and nonionic amphiphilic polymeric micelles for gene delivery.

关键词： polymeric micelle Block copolymer Gene delivery