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Zhanrong Li, Jingguo Li, Lei Zhu, Ying Zhang, Junjie Zhang, Lin Yao, Dan Liang, Liya Wang
The aim of the present study was to investigate the inhibitory effects of celastrol-loaded nanomicelles (CNMs) on activated macrophage-induced corneal neovascularization (CNV) in rats and cytokine secretion in macrophages. Using an angiogenesis assay in vitro, we detected the effects of CNMs on human umbilical vein endothelial cell (HUVEC) migration and invasion. In addition, the expression levels of cytokines secreted from hypoxia-induced macrophages were assessed through cytokine array analysis. The expression of hypoxia-inducible factors-1α (HIF-1α), nuclear factor-kappa B p65 (NF-κB p65), phospho-nuclear factor-kappa B p65 (phospho-NF-κB p65), p38 mitogen-activated protein kinase (p38 MAPK), phospho-p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2), and phospho-ERK1/2 was analyzed by western blotting...
2016: International Journal of Nanomedicine
Yue Gu, Jing Li, Yang Li, Lei Song, Dan Li, Liping Peng, Ying Wan, Shucheng Hua
PURPOSE: A new type of polymeric micelle (PM) was assembled using a polyethylene glycol (PEG)-linked (PEGylated) amphiphilic copolymer and d-tocopheryl PEG1000 succinate (TPGS1000). The micelles were used to deliver doxorubicin (DOX) and curcumin (CUR) for alleviating multidrug resistance (MDR) in lung cancer cells while enhancing the therapeutic efficacy of DOX. METHODS: Micelles loaded with DOX and CUR were assembled using a film-forming technique. Micelles were used to treat A549/Adr cells to find out whether micelles had the ability to reverse the MDR of A549/Adr cells...
2016: International Journal of Nanomedicine
Fiorella Carla Tesan, Mariano Gastón Portillo, Marcela Analía Moretton, Ezequiel Bernabeu, Diego Andrés Chiappetta, Maria Jimena Salgueiro, Marcela Beatriz Zubillaga
INTRODUCTION: In recent years, nanomedicines have raised as a powerful tool to improve prevention, diagnosis and treatment of different pathologies. Among the most well investigated biomaterials, D-α-tocopheryl polyethylene glycol succinate (also known as TPGS) has been on the spot for the last decade. We therefore designed a method to biologically characterize TPGS-based nanomicelles by labeling them with (99m)Tc. METHODS: Labeling process was performed by a direct method...
September 30, 2016: Nuclear Medicine and Biology
Lili Chen, Fangling Ji, Yongming Bao, Jing Xia, Lianying Guo, Jingyun Wang, Yachen Li
The greatest crux in the combination of chemotherapy and gene therapy is the construction of a feasible and biocompatible carrier for loading the therapeutic drug and gene simultaneously. Here, a new amphiphilic bifunctional pullulan derivative (named as PDP) synthesized by grafting lipophilic desoxycholic acid and low-molecular weight (1kDa) branched polyethylenimine onto the backbone of pullulan was evaluated as a nano-carrier for the co-delivery of drug and gene for potential cancer therapy. PDP exhibited good blood compatibility and low cytotoxicity in the hemolysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively...
January 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
Takanori Kanazawa, Takahiro Endo, Naoki Arima, Hisako Ibaraki, Yuuki Takashima, Yasuo Seta
This study aimed to build an innovative system to deliver a systemic small interfering RNA (siRNA) treatment for rheumatoid arthritis. We combined arginine-histidine-cysteine based oligopeptide-modified polymer micelles with siRNA targeting the nuclear factor κB subunit, RelA (siRelA). This is a key molecule in the control of inflammation. We tested the cellular uptake of siRNA and its effects on inflammatory cytokine levels in vitro using synoviocytes, and siRNA distribution and therapeutic effects in vivo in mice with collagen-induced arthritis (CIA)...
October 17, 2016: International Journal of Pharmaceutics
Junhui Zhou, Yidi Wu, Changrong Wang, Qiang Cheng, Shangcong Han, Xiaoxia Wang, Jianhua Zhang, Liandong Deng, Deyao Zhao, Lili Du, Huiqing Cao, Zicai Liang, Yuanyu Huang, Anjie Dong
The extremely low efficient cytosolic release of the internalized siRNA has emerged recently as a central issue for siRNA delivery, while there is a lack of guidelines to facilitate the cytosolic release of internalized siRNA. To address these concerns, we studied the contribution of the pH-sensitive inner core on handling the cytosolic release of siRNA delivered by a series of PG-P(DPAx-co-DMAEMAy)-PCB amphiphilic polycation nanomicelles (GDDC-Ms) with extremely low internalization (<1/4 of lipofactamine 2000 (Lipo2000))...
October 17, 2016: Nano Letters
Yanping Li, Rui Li, Qinhui Liu, Wenyao Li, Ting Zhang, Min Zou, Hong Li, Tong Wu, Shihai Cheng, Zhiguang Su, Zhirong Zhang, Jinhan He
Tumor cells can acquire multidrug resistance (MDR) as a result of drug efflux mediated by P-glycoprotein (P-gp). Here we report a targeted delivery system to carry pirarubicin (THP) to MDR breast cancer both in vitro and in vivo. PEG-derivatized vitamin E (PAMV6) amphiphiles loaded with THP were self-assembled in a single step. The PAMV6 micelles showed unimodal size distribution and high drug loading efficiency. Cytotoxicity of PAMV6/THP was higher than that of free THP on MCF-7/ADR cells but comparable to that of THP on MCF-7 cells...
October 15, 2016: Molecular Pharmaceutics
Amy Pan, Hongyong Zhang, Yuanpei Li, Tzu-Yin Lin, Fuli Wang, Joyce Lee, Mingshan Cheng, Marc Dall'Era, Tianhong Li, Ralph deVere White, Chong-Xian Pan, Kit S Lam
Chemotherapy commonly used in the treatment of advanced bladder cancer is only moderately effective and associated with significant toxicity. There has been no appreciable improvement in overall survival over the last three decades. The goal of this project is to develop and characterize bladder cancer-specific nanometer-scale micelles loaded with the chemotherapeutic drug paclitaxel (PTX) and determine the anti-tumor activity and toxicity. Micelle-building-material telodendrimers were synthesized through the stepwise conjugation of eight cholic acid units at one terminus of polyethylene glycol (PEG) and a bladder cancer-specific targeting peptide named PLZ4 at the other terminus...
October 21, 2016: Nanotechnology
Yu Liu, Jia Yang, Xin Wang, Ju Liu, Zhaobo Wang, Hongsheng Liu, Lijiang Chen
In this study, a controlled drug release system based on redox-responsive nanomicelles for drug delivery was described. The system was constructed by linking poly (acryic acid) (PAA) with D-α-tocopherol succinate (VES) via a disulfide bond linker (ss). This amphiphilic polymer (PAAssVES) was synthesized by coupling reaction and its chemical structure was confirmed by FT-IR and (1)HNMR analyses. PAAssVES was found to self-assemble into nanomicelles with diameter of about 130 nm, and a critical micelle concentration of about 6...
December 2016: Journal of Biomaterials Science. Polymer Edition
Yousra M El-Far, Mahmoud M Zakaria, Mahmoud M Gabr, Amal M El Gayar, Ibrahim M El-Sherbiny, Laila A Eissa
AIM: This study aimed to develop a new stable nanoformulation of silymarin (SM) with optimum enhanced oral bioavailability and to evaluate its effect as well as mechanism of action as a superior antidiabetic agent over native SM using streptozotocin-induced diabetic rats. MATERIALS AND METHODS: SM-loaded pluronic nanomicelles (SMnp) were prepared and fully characterized. Biochemical parameters were performed as well as histological, confocal and reverse-transcription polymerase chain reaction studies on pancreatic target tissues...
October 2016: Nanomedicine
Yufen Li, Yuanna Sun, Ying Xiao, Guorong Gao, Shuhui Liu, Jianfeng Zhang, Jun Fu
Multiresponsive polyelectrolyte hydrogels with extraordinary toughness have great potential in soft device applications. Previously we have demonstrated a series of tough and multiresponsive hydrogels by using multifunctional triblock copolymer (Pluronic F127 diacrylate, F127DA) micelles to cross-link cationic polyelectrolyte chains into 3D network. Herein, we further synthesize negatively charged hydrogels comprising 2-acrylamido-2-methyl propylsulfonic acid (AMPS) monomers by using F127DA micelles as cross-linkers...
October 5, 2016: ACS Applied Materials & Interfaces
Mingfu Gong, Hua Yang, Song Zhang, Yan Yang, Dong Zhang, Zhaohui Li, Liguang Zou
Tumor angiogenesis plays very important roles for tumorigenesis, tumor development, metastasis, and prognosis. Targeting T1/T2 dual modality magnetic resonance (MR) imaging of the tumor vascular endothelial cells (TVECs) with MR molecular probes can greatly improve diagnostic sensitivity and specificity, as well as helping to make an early diagnosis of tumor at the preclinical stage. In this study, a new T1 and T2 dual modality nanoprobe was successfully fabricated. The prepared nanoprobe comprise peptides CL 1555, poly(ε-caprolactone)-block-poly(ethylene glycol) amphiphilic copolymer shell, and dozens of manganese ferrite (MnFe2O4) nanoparticle core...
2016: International Journal of Nanomedicine
Neha N Parayath, Hayley Nehoff, Samuel E Norton, Andrew J Highton, Sebastien Taurin, Roslyn A Kemp, Khaled Greish
Oral administration of paclitaxel (PTX), a broad spectrum anticancer agent, is challenged by its low uptake due to its poor bioavailability, efflux through P-glycoprotein, and gastrointestinal toxicity. We synthesized PTX nanomicelles using poly(styrene-co-maleic acid) (SMA). Oral administration of SMA-PTX micelles doubled the maximum tolerated dose (60 mg/kg vs 30 mg/kg) compared to the commercially available PTX formulation (PTX [Ebewe]). In a murine orthotopic colon cancer model, oral administration of SMA-PTX micelles at doses 30 mg/kg and 60 mg/kg reduced tumor weight by 54% and 69%, respectively, as compared to the control group, while no significant reduction in tumor weight was observed with 30 mg/kg of PTX (Ebewe)...
2016: International Journal of Nanomedicine
Cheng-Liang Peng, Yuan-I Chen, Hung-Jen Liu, Pei-Chi Lee, Tsai-Yueh Luo, Ming-Jium Shieh
A novel thermosensitive polymer p(N-isopropylacrylamide-co-poly[ethylene glycol] methyl ether acrylate)-block-poly(epsilon-caprolactone), p(NIPAAM-co-PEGMEA)-b-PCL, was synthesized and developed as nanomicelles. The hydrophobic heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin and the photosensitizer cyanine dye infrared-780 were loaded into the core of the micelles to achieve both chemotherapy and photothermal therapy simultaneously at the tumor site. The release of the drug could be controlled by varying the temperature due to the thermosensitive nature of the micelles...
2016: International Journal of Nanomedicine
Hamid Reza Rahimi, Reza Nedaeinia, Alireza Sepehri Shamloo, Shima Nikdoust, Reza Kazemi Oskuee
OBJECTIVE: Curcumin is extracted from Curcuma longa and regulates the intracellular signal pathways which control the growth of cancerous cell, inflammation, invasion and apoptosis. Curcumin molecules have special intrinsic features that can target the intracellular enzymes, genome (DNA) and messengers (RNA). A wide range of studies have been conducted on the physicochemical traits and pharmacological effects of curcumin on different diseases like cardiovascular diseases, diabetes, cancer, rheumatoid arthritis, Alzheimer's, inflammatory bowel disease (IBD), and even it has wound healing...
July 2016: Avicenna Journal of Phytomedicine
Hengti Wang, Zhiang Fu, Wenyong Dong, Yongjin Li, Jingye Li
Micellization of in situ formed graft copolymers during reactive blending is commonly observed. Numerous studies have been carried out to minimize the formation of micelles and enhance emulsification efficiency. Herein, we investigated the formation of interfacial Janus nanomicelles (JNMs) and their compatibilization effects on immiscible polymer blends when reactive graft copolymers (RGCs) are used as compatibilizers. Poly(styrene-co-glycidyl methacrylate)-graft-poly(methyl methacrylate) RGCs were synthesized and used as compatibilizers for immiscible poly(l-lactide) (PLLA)/poly(vinylidene fluoride) (PVDF) blends...
September 1, 2016: Journal of Physical Chemistry. B
Liang Cheng, Anyanee Kamkaew, Haiyan Sun, Dawei Jiang, Hector F Valdovinos, Hua Gong, Christopher G England, Shreya Goel, Todd E Barnhart, Weibo Cai
Multifunctional nanoparticles with combined diagnostic and therapeutic functions show great promise in nanomedicine. Herein, we develop an organic photodynamic therapy (PDT) system based on polyethylene glycol (PEG)-coated nanomicelles conjugated with ∼20% chlorin e6 (PEG-Ce 6 nanomicelles), which functions as an optical imaging agent, as well as a PDT agent. The formed PEG-Ce 6 nanomicelles with the size of ∼20 nm were highly stable in various physiological solutions for a long time. Moreover, Ce 6 can also be a (64)Cu chelating agent for in vivo positron emission tomography (PET)...
August 23, 2016: ACS Nano
Marcel Wegmann, Luciano Parola, Facundo M Bertera, Carlos A Taira, Maximiliano Cagel, Fabian Buontempo, Ezequiel Bernabeu, Christian Höcht, Diego A Chiappetta, Marcela A Moretton
OBJECTIVES: Carvedilol (CAR) is a poorly water-soluble beta-blocker. Its encapsulation within nanomicelles (NMs) could improve drug solubility and its oral bioavailability, allowing the development of a paediatric liquid CAR formulation with commercially available copolymers: D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly(vinyl caprolactam)-poly(vinyl acetate)-poly(ethylene glycol) (Soluplus(®) ). METHODS: Drug-loaded NMs were prepared by copolymer and CAR dispersion in distilled water...
July 19, 2016: Journal of Pharmacy and Pharmacology
Xiuhua Li, Hui Shang, Wei Wu, Shuai Li, Zaifu Lin, Jiawei Duan, Lisa Xu, Jianshu Li
Recently, stimuli-responsive carriers have been paid much attention to control cargo release due to their obvious advantages such as targeted delivery, reduced systematic cytotoxicity and enhanced therapeutic efficiency. In this study, a well-defined block copolymer synthesized via ATRP, i.e., poly(ethylene glycol)-b-poly(2-diisopropylaminoethyl methacrylate) (PEG-b-PDPA), has been used to investigate the insulin release behavior in response to glucose changes for potential diabetes mellitus (DM) therapy. Based on the enzymatic catalytic reaction of glucose and glucose oxidase (GOD), the acidic product (gluconic acid) can reduce the micro-environmental pH value...
June 2016: Journal of Nanoscience and Nanotechnology
Long-Hai Wang, Ting Wu, De-Cheng Wu, Ye-Zi You
Cationic polymer vectors have received increasing attention for gene delivery in biotechnology over the past 2 decades, but few polymer vectors were used in clinical applications due to their low gene transfection efficacy. One of the major reasons is that the conventional cationic polymers can induce the increasing of intracellular reactive oxygen species (ROS) concentration and oxidative stress, which reduces the gene transfection efficacy. Here, we create a novel class of thioether dendron-branched polymer conjugate and self-assemble this conjugate into bioreducible cationic nanomicelles with disulfide bond connecting the thioether core to the cationic shell...
August 3, 2016: ACS Applied Materials & Interfaces
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