PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2022
·
IF 3.915
Yujia Liu,Xiaoyu Lu,Zhenhai Zhang,Shulong Jiang,Huixia Lv
In this study, amphiphilic block copolymer mPEG-cholic acid was synthesized in conjunction with TPGS as stabilizer to prepare multifunctional micelles. The formed polymeric micelles (PCTm) were used for the delivery of paclitaxel (PTX) and bufalin (BF). PEG group could enhance solubility and extend circulation time, while cholic acid groups achieved the liver targeted function. Combinations of these approaches could realize a synergistic therapeutic effect in the treatment of advanced hepatocellular carcinoma. CLSM in vitro results demonstrated that drug capsulation into PCTm could enhance cellular uptake. FCM results confirmed the uptake amount of C6/PCTm was 7.5-fold higher than that of free C6 after incubation for 2 h. Competitive inhibition test proved the Na+-taurocholate co-transporting polypeptide (NTCP) involved in the uptake mechanism of PCTm. Meanwhile, in vivo imaging assays demonstrated that the fluorescence intensity of Cy5.5/PCTm was higher than that of free Cy5.5 on liver and tumor with extended circulation time to 48 h. In addition, in vivo studies confirmed that the combined therapy exhibited the strongest tumor inhibition rate of 82.29% with lower systemic toxicity. Hence, these results indicated that PCTm could provide a promising strategy for targeting hepatocellular carcinoma and achieve the goal of synergism and attenuation.
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DOI
PubMed
高影响因子
POLYMER INTERNATIONAL
·
2022
·Vol. 71
·期 10
·1220-1229
·
IF 3.213
Jingjing Xiao,Yingying Lu,Lu Deng,Wulian Chen,Weiguo Hu,Yuqing Zhao,Shouzhen Chen
The preparation of polymer therapeutics capable of synergistic co-delivery systems for chemotherapeutic drugs and genes remains a tough problem in cancer therapy. Herein, we develop a novel co-delivery system for chemotherapeutic drugs and genes. Paclitaxel (PTX) was covalently grafted onto the cationic copolymer poly(ethylene glycol)- b -poly( l -lysine) (PEG- b -PLL) via a disulfide bond, and then CXCL1 shRNA was loaded on the cationic micelles PEG- b -PLL-SS-PTX by electrostatic interaction to construct PEG- b -PLL-SS-PTX/pDNA complex. The chemical structure of the complex was confirmed by gel permeation chromatography, 1 H NMR and Fourier transform infrared spectroscopy. The binding ability of the cationic micelles and pDNA was detected by gel retardation assay. In vitro gene transfection studies revealed an enhanced gene transfection efficiency due to the co-delivery of PTX and pDNA to ovarian cancer cells. In vitro and in vivo data demonstrated that the co-delivery complex exhibited a synergistic role of chemotherapy and gene therapy and possessed enhanced antitumor effects. The strategy of using drug-loaded cationic micelles as gene delivery carriers is a versatile approach to construct a co-delivery system, which might result in more efficient cancer therapy. © 2022 Society of Industrial Chemistry.
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DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Junxu Hao,Jinglei Wang,Hao Pan,Yuli Sang,Dazhuang Wang,Zeyu Wang,Jiao Ai,Bin Lin,Lijiang Chen
In this study, the ideal polymer materials were selected by molecular dynamics (MD) and dissipative particle dynamics (DPD) simulation methods, and pH and redox-sensitive micelles were prepared according to the simulation results. Through experiments, we successfully prepared hydrophilic block polyethylene glycol monomethyl ether (mPEG) connected hydrophobic block polylactic acid-glycolic acid (PLGA) amphiphilic polymer, and connected with redox fragment containing disulfide bond , and then connected with amide bond doxorubicin (DOX) to form mPEG-PLGA-SS-DOX prodrug , and further physical embedded free DOX. Finally, we obtained a particle size of 47.04 ± 0.103 nm, the potential of −23.8 ± 0.189 mV, Polymer dispersity index (PDI) of 0.231 ± 0.001, transmission electron microscopy (TEM) showed that it was spherical mPEG-PLGA-SS-DOX/DOX nanoparticles , its entrapment efficiency (EE) was 68.2%, loading content was 16.72%. The cumulative release of mPEG-PLGA-SS-DOX/DOX was 87.39% in a pH 5.0 and 10 mM Glutathione (GSH) tumor simulation environment. It was less toxic to normal cell HEK293 and more cytotoxic to HepG2 tumor cells. It showed that it was an excellent anti-tumor nano-drug. In addition, the application of computer simulation in the design of nanomedicine also provided a new research idea for the research of nanomedicine .
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DOI
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2019
·
IF 2.442
Yan Zheng,Shudan Shi,Yaru Liu,Yandan Zhao,Yuqi Sun
Liver cancer is one of the most common malignant tumors. Chemotherapy drugs have been widely used in the anti-hepatoma research. However, low targeting efficiency and serious adverse reaction are their main drawbacks. Liver tumor was proved to have a slightly acidic microenvironment (pH 4.5–5.5) and many glycyrrhetinic-acid-specific binding sites. Therefore, in the present study, the glycyrrhetinic acid- and hydrazone bond-modified micelles were designed. mPEG-HZ-PLA and GA-PEG-PLA copolymer were synthesized to prepare glycyrrhetinic-acid-modified pH-sensitive polymeric micelles (GA-PEG-HZ-PLA). The targeted pharmacokinetics was used to evaluate the effect in hepatoma 22 tumor-bearing mice after the micelles were administered intravenously. The contents of coumarin-6 in blood and tissues were determined through high-performance liquid chromatography using a fluorescence detection (HPLC-FLD) with coumarin-30 as inner standard. The micelles have shown long-circulation effects and two-department models. In the targeting pharmacokinetics, the relative intake efficiency, targeted efficiency, relative targeting efficiency, and concentration ratio of GA-PEG-HZ-PLA in the tumor were 3.24, 4.04, 3.00, and 2.47, respectively. We have demonstrated that GA-PEG-HZ-PLA was more effectively accumulated in the liver and tumor. Thus, the prepared active-targeted and pH-sensitive micelles modified with glycyrrhetinic acid structure and hydrazone bond are promising tools for effective liver cancer therapy.
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DOI
高影响因子
LANGMUIR
·
2021
·
IF 3.882
Qiong Guo,Jiangtao Liu,Hong Yang,Zhongli Lei
With the rapid development of nanotechnology, stimuli-responsive nanomaterials have provided an alternative for designing controllable drug delivery systems due to their spatiotemporally controllable properties. The environment of the human body is complex and cancer cells proliferate rapidly; the traditional nanocarriers could not release the loaded drugs sufficiently, and the release level of the drug is not sufficient for the requirement of treatment. Herein, a photoresponsive, glutathione, and reactive oxygen species block copolymer mPEG2k-ONB-SS-PO-mPEG2k is prepared by Cu(I)-catalyzed azide–alkyne cycloaddition click polymerization. The ο-nitrobenzyl groups, peroxalate ester bonds, disulfide bonds, and triazole units are regularly and repeatedly arranged in hydrophobic blocks. The photo, oxidative, and reductive responsive characteristics of the copolymers in different conditions were investigated by ultraviolet and visible spectrophotometry, dynamic light scattering, and transmission electron microscopy. Nile Red is encapsulated into the core of micelles as a model drug and exhibits the drug release behaviors in various environments. This research provides a way to design potential drug carriers and a promising platform for efficient intracellular drug delivery in cancer therapy.
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DOI
高影响因子
POLYMER
·
2015
·
IF 3.562
Lin Wang,Yin Wang,Qiao Jin,Fan Jia,Haibo Wang,Jian Ji
Biomimic hyaluronic acid (HA) prodrug micelles with pH and reduction responsiveness were prepared by chemical graft of phosphorylcholine and doxorubicin (DOX) to the backbone of HA. DOX was conjugated to HA by pH-sensitive hydrazone bonds which could be hydrolyzed under acidic conditions and thus resulted in controlled release of DOX. Besides, the HA prodrug micelles were cross-linked via reduction-responsive disulfide bonds to improve the stability of the micelles. The HA prodrug can form remarkable core–shell micelles with a quite narrow size distribution which was confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The in vitro drug release studies showed that there was a dramatic release under endosome pH (pH = 5.0) and reductive environment (10 mM of dithiothreitol) than that at normal physiological environment (pH = 7.4). Greater uptake of DOX from HA prodrug micelles was observed in the CD44 receptor highly expressed MDA-MB-231 cell line, compared to the results from the CD44-negative cell line, NIH3T3, which was demonstrated by the flow cytometry and fluorescence microscopy . The glutathione (GSH)-responsive behaviors were studied as well. The micelles showed higher cellular proliferation inhibition against glutathione monoester (GSH-OEt) pretreated MDA-MB-231 cells than that of the non-pretreated and buthionine sulfoximine (BSO) pretreated ones. These results suggested that such pH/reduction dual-responsive prodrug micelles may enhance the selective inhibition to cancer cells which exhibit higher levels of GSH concentration and provide favorable platforms for cancer therapy.
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DOI
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2016
·
IF 2.76
Jin Feng,Shanshan Wu,Hua Wang,Songbai Liu
Improved capability to inhibit degradation of trianionic curcumin has been realized in this study. The interaction between trianionic curcumin (Cur 3− ) and gemini dodecyl or tetradecyl O -glucoside micelles , tetradecyltrimethylammonium chloride (TTAC) or hexadecyltrimethylammonium bromide (CTAB) micelles as well as gemini alkyl O -glucosides (AGs)/alkyl trimethyl ammonium halides mixed micelles have been characterized. It is demonstrated that Cur 3− cannot be incorporated into gemini AGs micelles since the lack of electrostatic attraction and degraded as rapidly as in aqueous phase. Cur 3− tend to reside at palisade layer − water interface of TTAC or CTAB micelles due to the strong electrostatic interaction while moderate electrostatic interaction allows Cur 3− to locate more deeply in the palisade layer of mixed micelles. Additionally, mixed micelles tend to form a more compact and hydrophobic palisade layer than pure TTAC and CTAB ones. These factors bring about enhanced fluorescence intensity and blue − shift of emission maxima, improved fluorescence anisotropy and quantum yield, as well as reduced decay rate of Cur 3− in mixed micelles than in pure TTAC and CTAB ones.
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DOI
高影响因子
FOOD CHEMISTRY
·
2013
·
IF 3.334
Wenjian Li,Hailong Peng,Fangjian Ning,Lihua Yao,Mei Luo,Qiang Zhao,Xuemei Zhu,Hua Xiong
Novel amphiphilic chitosan derivative of N , N -dimethylhexadecyl carboxymethyl chitosan (DCMCs) was synthesised. The physical properties of DCMCs were characterised by Fourier transform-infrared spectroscopy, nuclear magnetic resonance spectroscopy, X-ray diffraction and differential scanning calorimetry. DCMCs can form core–shell micelles with low critical micelle concentration (31 mg L −1 ). The core–shell micelles exhibited spherical shape with positive charge (+50.7 mV) and narrow size distribution (polydispersity index <0.5). Vitamin D 3 (VD 3 ) was initially used to load into the core–shell micelles, and the solubility of VD 3 was improved with higher encapsulation efficiency (53.2%). The in vitro release processes of VD 3 from the core–shell micelles were initially rapid and then followed by a sustained release. The Higuchi model was the most suitable for describing the entire release procedure. DCMCs core–shell micelles are promising carriers for VD 3 and other hydrophobic bioactive food factors.
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DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2021
·
IF 5.89
Yu Juan,Xu Chaoqun,Lu Chuanwei,Liu Qian,Wang Jifu,Chu Fuxiang
Preparation and application of sustainable polymers derived from renewable resources are of great significance. The aim of this study is to synthesize a kind of sustainable polymeric micelles from rosin and vegetable oils via atom transfer radical polymerization (ATRP) and to investigate the doxorubicin delivery properties of these micelles. Dehydroabietic acid–based poly lauryl methacrylate (DA-PLMA) with narrow PDI of 1.13 was prepared in a well-controlled process using rosin as an ATRP initiator. Thereafter, carboxylic groups were introduced to form poly methacrylic acid (PMAA) moieties in DA-PLMA polymer via acid hydrolysis. The resulted DA-PLMA-PMAA could self-assemble in water to form pH-dependent polymeric micelles with a diameter of ∼65 nm and PDI as low as 0.105. Owing to the existence of rosin, DA-PLMA-PMAA micelles also showed self-fluorescence properties. In addition, Dox-loaded micelles were prepared in aqueous solution with the drug-loading capacity as high as 16.0% and showed sustained-release characteristics. These results demonstrate great promise for designing polymeric micellar from rosin and vegetable oils.
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DOI
高影响因子
BIOCONJUGATE CHEMISTRY
·
2014
·
IF 4.821
Jinwen Li,Yanxia Zhou,Chengwei Li,Dishi Wang,Yajie Gao,Chao Zhang,Lei Zhao,Yushu Li,Yan Liu,Xinru Li
Dual endosomal pH-sensitive micelles were designed and fabricated to deliver doxorubicin (DOX) for treating breast cancer based on a poly(2-ethyl-2-oxazoline) (PEOz)–DOX (PEOz–hyd–DOX) conjugate. PEOz–hyd–DOX was successfully synthesized by connecting DOX to PEOz via an acid cleavable hydrazone linker and self-assembled into nanosized micelles, which further physically encapsulated DOX. The conjugate and DOX-loaded conjugate micelles displayed faster release of DOX at pH 5.0 than at pH 7.4. This pH-dependent release behavior might assist the quick diffusion of DOX from acidic endosomes or lysosomes and the intracellular transfer into the nucleus after internalization, which was confirmed by confocal laser scanning microscopy images. As expected, PEOz–hyd–DOX conjugate and DOX-loaded conjugate micelles maintained cytotoxicity of DOX. In addition, the dual endosomal pH-sensitive micelles were found to substantially enhance antitumor efficacy and reduce side effects compared with free DOX. Therefore, PEOz–hyd–DOX conjugate-based micelles might be potential drug delivery vehicles of DOX for safe and effective breast cancer therapy.
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DOI
高影响因子
JOURNAL OF DISPERSION SCIENCE AND TECHNOLOGY
·
2025
·
IF 1.9
Chenning Su,Guozheng Wang,Jianzhong Jiang
Smart wormlike micelles (WLMs) that respond to environmental stimuli and display tunable rheological properties have attracted considerable interest. However, the responsive surfactants in the smart WLMs are always commercially unavailable. Herein, we report the preparation of CO2/N2 and redox dual-stimuli responsive wormlike micelles (WLMs) using sodium ferrocenecarboxylic acid (FA), hexadecyl trimethyl ammonium bromide (CTAB), and N,N-dimethylhexadecylamine (CDA), which are all commercially available compounds. The ferrocene group in FA can be reversibly switched between its oxidized and reduced forms by redox reactions, which would alter the hydrophilic properties of FA. Consequently, by alternately adding H2O2 and NaBH4, WLMs can be reversibly destoryed and reformed because of the redox-responsiveness of FA. Moreover, WLMs can also be switched on and off by cyclically bubbling CO2 and N2, resulting from the reversible protonation of CDA. The multi-stimuli responsive WLMs (CTAB-FA-CDA) may have potential applications in oil recovery and fluid drag reducers.
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DOI
高影响因子
Pharmaceutics
·
2025
·Vol. 17
·期 3
·302
·
IF 5.5
Jing Zhang,Min Zha,Anping Wan,Satya Siva Kishan Yalamarty,Nina Filipczak,Xiang Li
Background Despite many studies on polymer-incorporated nanocarriers for ophthalmic drug delivery, few have thoroughly explored the relationship between coating composition and performance. This study aimed to evaluate the effects of three commonly used cationic polymers—distearoyl phosphatidylethanolamine-polyethylene glycol 1000-poly(amidoamine) (DSPE-PEG1000-PAMAM), trimethyl chitosan (TMC), and (2,3-dioleoyloxypropyl) trimethylammonium chloride (DOTAP)—on the corneal behaviors and anti-cataract efficacy of diosmetin (DIO)-loaded micelles (D-M-P, D-M-T, and D-M-D, respectively). Methods The DIO-loaded micelles were prepared using the thin-film dispersion method and incorporated with the three polymers through hydrophobic interactions and electrostatic adsorption. Structural characterization was demonstrated by TEM imaging and particle size analyzer. In vitro release behavior was detected by the dialysis method. Cell viability of D-M-P, D-M-T, and D-M-D on L929 cells was detected by CCK-8 assays, with cellular uptake performed using coumarin 6 as the fluorescence indicator. Precorneal retention behaviors of these three vesicles were observed by In Vivo Imaging System. Transcorneal permeability was determined by modified Franz diffusion method and the permeation routes of the vesicles are investigated. Selenite-induced cataract model was established. The anti-cataract effects of three different DIO-loaded micelles were evaluated by the observation of lens opacity and antioxidant enzyme activities. Eye Irritation of the DIO in different preparations was estimated using the Draize test, along with H&E staining of the corneas. Results Structural characterization of DIO-loaded micelles revealed that the vesicles were spherical, with a uniform size distribution of around 28 nm, a similar surface potential of approximately 6.0 mV, and a high DIO entrapment efficiency of about 95%. Compared to the DIO suspension, all three formulations exhibited a significant sustained-release effect. They showed no signs of irritation and demonstrated increased IC50 values in L929 cells, indicating improved biocompatibility. Cellular uptake in human lens epithelial cells (HLECs) was assessed using confocal laser scanning microscopy. C-M-T displayed the highest fluorescence signals, with a cellular internalization 3.2 times greater than that of the solution group. Both C-M-T and C-M-P enhanced vesicle retention on the corneal surface by at least 47.8% compared to the Cou-6 solution. Furthermore, TMC facilitated the paracellular transport of vesicles into the deepest layers of the cornea and delivered DIO across the cornea, with a P app value 3.11 times and 1.49 times those of D-M-D and D-M-P, respectively. In terms of therapeutic efficacy, D-M-T demonstrated the most significant attenuation of lens opacity, along with enhanced antioxidant enzyme activities and inhibition of lipid peroxidation. Conclusion The modification of micelle vesicles with different cationic polymers significantly influences their performance in ocular drug delivery. Among the tested formulations, D-M-T stands out due to its multiple advantages, including enhanced transcorneal drug delivery, therapeutic efficacy for DIO, and safety, making it the most promising candidate for ophthalmic applications.
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高影响因子
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