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CD-PEI
INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2015 · IF 3.65

Improvement of pulmonary absorption of poorly absorbable macromolecules by hydroxypropyl-β-cyclodextrin grafted polyethylenimine (HP-β-CD-PEI) in rats

Hailong Zhang,Xiaoyan Huang,Ya Sun,Guangyou Lu,Ke Wang,Zhigang Wang,Jianfeng Xing,Yang Gao

Effects of hydroxypropyl-β-cyclodextrin grafted polyethylenimine (HP-β-CD-PEI) including HP-β-CD-PEI 600 , HP-β-CD-PEI 1800 , HP-β-CD-PEI 10000 on the pulmonary absorption of insulin, calcitonin, 5(6)-carboxyfluorescein (CF) and fluorescein isothiocyanate dextrans (FDs) with various molecular weights (FD4, FD10 and FD70) were examined by an pulmonary absorption study in rats. Pulmonary absorptions of these poorly absorbable drugs were significantly enhanced by HP-β-CD-PEI 1800 and HP-β-CD-PEI 10000 , and HP-β-CD-PEI 1800 with the concentration of 5% (w/v) provided maximal absorption enhancing effect on pulmonary absorption of these model drugs. The toxicity study demonstrated that HP-β-CD-PEI did not induce any toxic action to rat pulmonary membranes. In addition, zeta potential of insulin solution changed to positive by addition of various HP-β-CD-PEI, meanwhile, the degree of positive charge was linearly correlated with absorption enhancing effect of HP-β-CD-PEI, suggesting that positive charge of HP-β-CD-PEI might be related to their absorption enhancing mechanisms for enhancing pulmonary absorption of insulin in rats. In conclusion, HP-β-CD-PEI is a potential and safe absorption enhancer for improving absorption of hydrophilic macromolecules especially peptide and protein drugs by pulmonary delivery.

研究领域: 药理学 · 生物医学工程
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COMPOSITES PART B-ENGINEERING · 2022 · IF 11.322

β-CD/PEI/PVA composite hydrogels with superior self-healing ability and antibacterial activity for wound healing

Dan Liu,Jiajun Qiu,Ru Xu,Junyu Liu,Jiayin Feng,Liping Ouyang,Shi Qian,Yuqin Qiao,Xuanyong Liu

Bacterial infections in wounds often delay the healing process which threaten human health and life. The development of biocompatible hydrogels with antibacterial activity and self-healing to achieve excellent wound closure effectiveness is highly desirable in clinical applications. Herein, a new class of highly stretchable, biocompatible, and antibacterial hydrogel dressings called BPP hydrogel is designed and prepared by chemically cross-linking β-CD with PEI and then physically cross-linking with PVA. The BPP hydrogel exhibits superior properties including excellent antibacterial properties against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli , good biocompatibility for mouse fibroblasts , mouse embryonic fibroblasts and human umbilical vein endothelial cells, outstanding deformability and self-healing performance to protect the wound completely even in special scenes such as pulling and bending. Besides, after damage, the broken BPP hydrogel could heal together, and the healed BPP hydrogel could be stretched to 150% breaking deformation. Furthermore, in vivo experiments further verify that BPP hydrogel has excellent sterilization and healing effect on infectious wounds. This work proves that BPP hydrogel would be a promising material for wound healing and has good prospect for clinical translation.

研究领域: 材料科学 · 医学 · 生物工程
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DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY · 2016 · IF 2.429

Efficacy, safety and mechanism of HP-β-CD-PEI polymers as absorption enhancers on the intestinal absorption of poorly absorbable drugs in rats

Hailong Zhang,Xiaoyan Huang,Yongjing Zhang,Yang Gao

Context: Oral bioavailability of some hydrophilic therapeutic macromolecules was very poor, thus leading to their limited application in clinic.Objective: To investigate the efficacy, safety and mechanism of HP-β-CD-PEI polymers on the intestinal absorption of some poorly absorbable drugs in rats.Methods: Effects of HP-β-CD-PEI polymers on the intestinal absorptions of drugs were investigated by an in situ closed loop method in rats. The safety of HP-β-CD-PEI polymer was evaluated by measurement of lactate dehydrogenase (LDH) activity and amount of protein released from rat intestinal perfusate. The absorption enhancing mechanisms were explored by the measurement of zeta potential, transepithelial electrical resistance (TEER) and in vitro transport of FD4 (a paracellular marker) across rat intestinal membranes, respectively.Results: HP-β-CD-PEI polymers, especially HP-β-CD-PEI1800, demonstrated excellent absorption enhancing effects on drug absorption in a concentration-dependent manner and the enhancing effect was more efficient in the small intestine than that in the large intestine. Five percent (w/v) HP-β-CD-PEI1800 obviously decreased the TEER, accompanied with increase in the intestinal transport of FD4, indicating that absorption enhancing actions of HP-β-CD-PEI polymers were possibly performed by loosening tight junctions of intestinal epithelium cells, thereby increasing drug permeation via a paracellular pathway. A good liner relationship between absorption enhancing effects of HP-β-CD-PEI polymers and their zeta potentials suggested the contribution of positive charge on the surface of these polymers to their absorption enhancing effects.Conclusion: HP-β-CD-PEI polymers might be potential and safe absorption enhancers for improving oral delivery of poorly absorbable macromolecules including peptides and proteins.

CAS / MDL: 47931-85-1 11061-68-0
研究领域: 药剂学 · 药物递送 · 药理学
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Analytical Methods · 2021 ·Vol. 13 ·期 17 ·2011-2020 · IF 2.896

Supramolecular assembly induced chiral interface for electrochemical recognition of tryptophan enantiomers

Yi-Xin Sun,Dan-Dan Zhang,Yang Sheng,Defeng Xu,Rong Zhang,Mark Bradley

The β-CD@PEI-Fc chiral interface was prepared based on the supramolecular host–guest interaction between ferrocene (Fc) grafted polyethyleneimine (PEI-Fc) and chiral β-cyclodextrin (β-CD). SEM results show that β-CD@PEI-Fc interface has a regular spatial structure, which can effectively distinguish tryptophan (Trp) enantiomers. Under the optimal conditions, differential pulse voltammetry shows that the peak current ratio (ID/IL) of Trp enantiomers can reach 2.84 at 15 °C. More interestingly, the β-CD@PEI-Fc/GCE exhibited chiral recognition of D-Trp and L-Trp via water contact angle measurements. There was a good linear relationship between the peak current and the concentration of Trp enantiomers in the range from 0.005 mM to 0.10 mM. Finally, the chiral interface can be applied for quick detection of the proportion of isomers in Trp racemic solution, which is very important for chiral recognition in racemic mixture of chiral compounds. Meanwhile, the β-CD@PEI-Fc/GCE showed good stability and reproducibility.

研究领域: 分析化学 · 电化学 · 手性 · 材料科学
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International Journal of Polymeric Materials and Polymeric Biomaterials · 2021 · IF 2.604

Fluorescent carbon dots loading nitric oxide for bacterial labeling and killing

Ziheng Chen,Song Peng,Shixin Liu,Chengpeng Li,Xiang Cai,Dong Ma,Wu Zhang

Bacterial infection is a serious threat to human health. In this work, carbon dots (CDs) based on the polyethyleneimine (PEI) was prepared by hydrothermal carbonization method and then reacted with nitric oxide (NO) to form the NO-loaded CDs (CD-PEI/NONOate). CD-PEI/NONOate showed a high NO payload and outstanding fluorescence characteristics. It was found that CD-PEI/NONOate could inhibit the growth of Gram-negative bacteria Pseudomonas aeruginosa by more than 99%. Moreover, CD-PEI/NONOate showed no cytotoxicity to 3T3 cells at concentrations used in vitro. These results indicated that the prepared CD-PEI/NONOate has a potential application in the diagnosis and treatment of bacterial infection.

CAS / MDL: 9002-98-6 6119-70-6
研究领域: 材料科学 · 微生物学 · 生物医学工程
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ACS Applied Materials & Interfaces · 2020 · IF 8.758

A Sequentially Responsive Nanosystem Breaches Cascaded Bio-barriers and Suppresses P-Glycoprotein Function for Reversing Cancer Drug Resistance

Jia Liu,Lei Zhao,Lin Shi,Ye Yuan,Daan Fu,Zhilan Ye,Qilin Li,Yan Deng,Xingxin Liu,Qiying Lv,Yanni Cheng,Yunruo Xu,Xulin Jiang,Guobin Wang,Lin Wang,Zheng Wang

Cancer chemotherapy is challenged by multidrug resistance (MDR) mainly attributed to overexpressed transmembrane efflux pump P-glycoprotein (P-gp) in cancer cells. Improving drug delivery efficacy while co-delivering P-gp inhibitors to suppress drug efflux is an often-used nanostrategy for combating MDR, which is however challenged by cascaded bio-barriers en route to cancer cells and P-gp inhibitors’ adverse effects. To effectively breach the cascaded bio-barriers while avoiding P-gp inhibitors’ adverse effects, a stealthy, sequentially responsive doxorubicin (DOX) delivery nanosystem (RCMSNs) is fabricated, composed of an extracellular-tumor-acidity-responsive polymer shell (PEG-b-PLLDA), pH/redox dual-responsive mesoporous silica nanoparticle-based carriers (MSNs-SS-Py), and cationic β-cyclodextrin-PEI (CD-PEI) gatekeepers. The PEG-b-PLLDA corona makes RCMSNs stealthy with prolonged blood circulation time. Once tumors are reached, extracellular acidity degrades PEG-b-PLLDA, reversing nanosystem’s surface charges to be positive, which drastically improves RCMSNs’ tumor accumulation, penetration, and cellular internalization. Within cancer cells, CD-PEI gatekeepers detach to allow DOX unloading in response to intracellular acidity and glutathione and functionally act as a P-gp inhibitor, dampening P-gp’s efflux activity by impairing ATP production. Thus, the resultant high-efficacy drug delivery along with reduced P-gp function cooperatively reverses MDR in vitro. Importantly, in preclinical tumor models, DOX@RCMSNs potently suppress MDR tumor growth without eliciting systemic toxicity, demonstrating their potential of clinical translation.

研究领域: 纳米技术 · 药学 · 肿瘤学 · 生物医学工程 · 药物递送系统 · 癌症治疗
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

Multistage Anticoagulant Surfaces: A Synergistic Combination of Protein Resistance, Fibrinolysis, and Endothelialization

Jian Feng,Jinghong Wang,Huanhuan Wang,Xinyin Cao,Xiaoliang Ma,Yu Rao,Huimin Pang,Sulei Zhang,Yuheng Zhang,Lei Wang,Xiaoli Liu,Hong Chen

Anticoagulant surface modification of blood-contacting materials has been shown to be effective in preventing thrombosis and reducing the dose of anticoagulant drugs that patients take. However, commercially available anticoagulant coatings, that is, both bioinert and bioactive coatings, are typically based on a single anticoagulation strategy. This puts the anticoagulation function of the coating at risk of failure during long-term use. Considering the several pathways of the human coagulation system, the synergy of multiple anticoagulation theories may provide separate, targeted effects at different stages of thrombosis. Based on this presumption, in this work, negatively charged poly(sodium p-styrenesulfonate-co-oligo(ethylene glycol) methyl ether methacrylate) and positively charged poly(lysine-co-1-adamantan-1-ylmethyl methacrylate) were synthesized to construct matrix layers on the substrate by electrostatic layer-by-layer self-assembly (LBL). Amino-functionalized β-cyclodextrin (β-CD-PEI) was subsequently immobilized on the surface by host–guest interactions, and heparin was grafted. By adjusting the content of poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA), the interactions between modified surfaces and plasma proteins/cells were regulated. This multistage anticoagulant surface exhibits inertness at the initial stage of implantation, resisting nonspecific protein adsorption (POEGMA). When coagulation reactions occur, heparin exerts its active anticoagulant function in a timely manner, blocking the pathway of thrombosis. If thrombus formation is inevitable, lysine can play a fibrinolytic role in dissolving fibrin clots. Finally, during implantation, endothelial cells continue to adhere and proliferate on the surface, forming an endothelial layer, which meets the blood compatibility requirements. This method provides a new approach to construct a multistage anticoagulant surface for blood-contacting materials.

研究领域: 材料科学 · 生物材料 · 生物医学工程 · 表面化学 · 止血 · 血栓
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