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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Synthesis of β-acids loaded chitosan-sodium tripolyphosphate nanoparticle towards controlled release, antibacterial and anticancer activity

Bingren Tian,Xia Qiao,Songlin Guo,Aiqin Li,Yanan Xu,Jia Cao,Xu Zhang,Duan Ma

The development of nanoparticles loaded with natural active ingredients is one of the hot trends in the pharmaceutical industry. Herein, chitosan was selected as the base material, and sodium tripolyphosphate was chosen as the cross-linking agent. Chitosan nanoparticles loaded with β-acids from hops were prepared by the ionic cross-linking method. The results of Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) indicated that chitosan nanoparticles successfully encapsulated β-acids. The loading capacity of chitosan nanoparticles with β-acids was 2.00 %–18.26 %, and the encapsulation efficiency was 0.58 %–55.94 %. Scanning electron microscopy (SEM), transmission electron microscope (TEM), particle size, and zeta potential results displayed that the nanoparticles revealed a sphere-like distribution with a particle size range of 241–261 nm, and the potential exhibited positive potential (+14.47–+16.27 mV). The chitosan nanoparticles could slowly release β-acids from different simulated release media. Notably, the β-acids-loaded nanoparticles significantly inhibited Staphylococcus aureus ATCC25923 ( S. aureus ) and Escherichia coli ATCC25922 ( E. coli ). Besides, β-acids-loaded chitosan nanoparticles were cytotoxic to colorectal cancer cells (HT-29 and HCT-116). Therefore, applying chitosan nanoparticles can further expand the application of β-acids in biomedical fields.

CAS / MDL: 51-21-8
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Food and Bioprocess Technology · 2023 · IF 5.6

Ternary Complex Microparticles Assembled from Vanillin, γ-Cyclodextrin, and Dextran: Fabrication, Structure, and Controlled Release Characteristics

Liu Yikun,Liao Li,McClements David Julian,Chen Xing,Cao Mengmeng,Liang Ruihong,Zou Liqiang,Liu Wei

Vanilla is one of the most widely used flavors in the food and beverage industry; however, it is thermally unstable and volatile. In this study, microparticles consisting of ternary complexes of vanillin/γ-cyclodextrin/dextran (V/C/D) were prepared, in which vanillin served as a crosslink between the γ-cyclodextrin and dextran. One end of vanillin was inserted into the interior of γ-cyclodextrin through hydrophobic interactions and hydrogen bonding, while the other end was bound to dextran through hydrogen bonding. The encapsulation efficiency of vanillin in the microparticles increased from around 59 to 92% when the mass ratio of dextran in the complexes increased (V/C/D ratio ranging from 1:9:0 to 1:5:4). Moreover, the crystallization peak of vanillin disappeared in complexes with higher dextran contents. The dispersibility of vanillin in cold water (4 ℃) increased as the dextran content in the complexes increased, with the highest value being 15 mg/mL. Encapsulation of vanillin within the microparticles protected it from volatilization during storage, with more than 90% being retained after holding at 60 ℃ for a month, as well as increasing its resistance thermal processing. The release of vanillin during baking (200 ℃, 30 min) could be controlled by altering the composition of the microparticles. Our findings provide a novel strategy for improving the stability and controlling the release of aromas. Graphical Abstract

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ChemPlusChem · 2023 ·Vol. 88 ·期 11 ·e202300387 · IF 3.4

Facile Fabrication of Dual-Activatable Gastrointestinal-Based Nanocarriers for Safe Delivery and Controlled Release of Methotrexate

Shuai Chen,Zheng-Quan Nie,Fang-Dao Zhu,Cui-Ting Yang,Jian-Mei Yang,Jun-Nan He,Xiao-Qing Liu,Jin Zhang,Yan Zhao

Graphical An oral gastrointestinal-based anticancer nanocarrier (Am7CD/SDS NPs) was equipped with both pH and temperature sensitivity, which could effectively prevent MTX@Am7CD/SDS NPs from being degraded in the acidic environment mimicking the stomach and small intestine, thus harboring the potential to accumulate at the site of colon lesions and further release drugs under mild conditions. Colon cancer is emerging as one of the most common cancers worldwide, ranking in the top three in morbidity and mortality. Oral methotrexate (MTX) has been employed as a first-line treatment for various cancers, such as colon, breast, and lung cancer. However, the complexity and particularity of the gastrointestinal microenvironment and the limitations of MTX itself, including severe adverse effects and instability, are the main obstacles to the safe delivery of MTX to colon tumor sites. Herein, an innovative oral administrated anticancer therapeutic MTX@Am7CD/SDS NPs equipped with both pH and temperature sensitivity, which could effectively prevent MTX@Am7CD/SDS NPs from being degraded in the acidic environment mimicking the stomach and small intestine, thus harboring the potential to accumulate at the site of colon lesions and further release intestinal drug under mild conditions. In cellular assays, compared with free MTX, MTX@Am7CD/SDS NPs showed a favorable tumor inhibition effect on three tumor cell lines, as well as excellent cell uptake and apoptosis-inducing effect on SW480 cells. Therefore, this work provides a feasible solution for the safe use of MTX in the treatment of colon cancer and even other intestinal diseases.

CAS / MDL: 7585-39-9 151-21-3
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PLoS One · 2014 ·Vol. 9 ·期 12 ·e113797 · IF 3.534

A Novel Controlled-Release System for Antibacterial Enzyme Lysostaphin Delivery Using Hydroxyapatite/Chitosan Composite Bone Cement

Bai Xue,Cheng Zhang,Yihan Wang,Jincheng Wang,Jien Zhang,Min Lu,Guodong Li,Zhizhong Cao,Qingshan Huang

In this work, a lysostaphin-loaded, control-released, self-setting and injectable porous bone cement with efficient protein delivery was prepared by a novel setting method using hydroxyapatite/chitosan (HA/CS) composite scaffold. The cement samples were made through cementitious reactions by mixing solid powder, a mixture of HA/CS composite particles, lysostaphin, Ca(OH) 2 , CaCO 3 and NaHCO 3 , with setting liquid containing citric acid, acetic acid, NaH 2 PO 4 , CaCl 2 and poloxamer. The setting parameters of the cement samples were determined. The results showed that the final setting time was 96.6±5.2 min and the pH value increased from approximately 6.2 to nearly 10 during the setting process and the porosity was 34% at the end. And the microstructure and composition were detected by scanning electron microscopy (SEM), x-ray diffraction and Fourier transform-infrared spectroscopy. For the release behavior of lysostaphin loaded in the cement sample, the in vitro cement extract experiment indicated that about 94.2±10.9% of the loaded protein was released before day 8 and the in vivo Qdot 625 fluorescence tracking experiment showed that the loaded protein released slower than the free one. Then the biocompatibility of the cement samples was evaluated using the methylthiazol tetrazolium assay, SEM and hematoxylin-eosin staining, which suggested good biocompatibility of cement samples with MC 3T3-E1 cells and subcutaneous tissues of mice. Finally the antibacterial activity assay indicated that the loaded lysostaphin had good release ability and strong antibacterial enzymatic activity against methicillin-resistant Staphylococcus aureus . Collectively, all the results suggested that the lysostaphin-loaded self-setting injectable porous bone cement released the protein in a controlled and effective way and the protein activity was well retained during the setting and releasing process. Thus this bone cement can be potentially applied as a combination of artificial bone substitute and controlled-release system for delivery of lysostaphin to treat bone defects and infections.

CAS / MDL: 25389-94-0 3810-74-0
研究领域: 材料科学 · 生物医学工程 · 药剂学
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Polymer Chemistry · 2014 ·Vol. 6 ·期 10 ·1817-1829 · IF 5.368

Self-assembly and disassembly of a redox-responsive ferrocene-containing amphiphilic block copolymer for controlled release

Lichao Liu,Leilei Rui,Yun Gao,Weian Zhang

Stimuli-responsive block copolymer micelles have recently emerged as promising drug delivery systems with controllable drug release. Herein, we report well-defined redox-responsive ferrocene-containing amphiphilic block copolymers PEG-b-PMAEFc, which were synthesized by the atom transfer radical polymerization (ATRP) of 2-(methacryloyloxy) ethyl ferrocene-carboxylate (MAEFc) using a PEG-based macro-ATRP agent. These block copolymers can self-assemble into various interesting nanostructures in aqueous solution. The self-assembled morphology of amphiphilic block copolymers is influenced by the nature of the common solvents used, the polymer composition and concentration, and the addition of β-cyclodextrin (β-CD) and redox agents (H2O2 and KMnO4), the effects of which were investigated by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Furthermore, the redox agent H2O2 can be used to trigger the release of encapsulated cargo (Rhodamine B) in the polymeric nanocarriers. This redox behavior of the amphiphiles could open up an approach for redox-controlled drug delivery systems.

研究领域: 材料科学 · 聚合物化学 · 纳米技术 · 药学
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION · 2015 · IF 1.648

Synthesis of poly(glutamic acid)-tyramine hydrogel by enzyme-mediated gelation for controlled release of proteins

Zhiping Peng,Yingqi She,Lei Chen

An in situ-formed hydrogel was synthesized by enzymatic cross-linking of poly(γ-glutamic acid)–tyramine conjugates (PGA–Tyr) using horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). The gelation time ranged from 25 s to 5 min was accomplished by tuning the concentration of HRP, H2O2/Tyr molar ratio and the degree of substitution (DS) of Tyr groups. The storage modulus (G′), cross-link density, and mesh size can be tailored by controlling the H2O2/Tyr ratio and DS. The rheological analysis indicated that the storage modulus (G′) can be tailored from approximately 40 to over 1100 Pa with the increasing H2O2/Tyr ratio and DS. The bovine serum albumin (BSA) was used as model protein and encapsulated into the hydrogel during the enzyme-mediated cross-linking reaction. Controlled release of BSA in vitro from the PGA–Tyr hydrogel was obtained. The release rate and cumulative release amount of encapsulated BSA were manipulated by controlling the H2O2/Tyr ratio and DS. More than 90% of encapsulated BSA was released from the hydrogel with low cross-link density and lager mesh size in 60 h, while only 68% of BSA was released from the hydrogel with high cross-link density and small mesh size. The results indicated that the PGA–Tyr hydrogel is a promising material for the controlled release of therapeutic protein or peptides.

研究领域: 材料科学 · 生物医学工程 · 药学
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Materials · 2015 ·Vol. 8 ·期 2 ·379-391 · IF 2.651

Preparation of pH Sensitive Pluronic-Docetaxel Conjugate Micelles to Balance the Stability and Controlled Release Issues

Yanchao Liang,Zhihui Su,Yao Yao,Na Zhang

A novel polymer-drug conjugate was prepared by the chemical reaction between the copolymer Pluronic P123 and the docetaxel via a pH sensitive hydrazone bond. These pluronic P123-docetaxel (DTX) conjugates (P123-DTX) could form the stable drug-loaded materials that can self-assemble into the defined nano-micelles in aqueous solution because of their obvious amphiphilic property and low critical micelle concentration. The spherical morphology and particle size of the prepared nano-micelles were characterized by transmission electron microscopy and dynamic light scattering, respectively. Moreover, after the introduction of pH sensitive hydrazone bond, P123-DTX micelle showed a pH dependent drug release behavior. At pH 5.0 (in 48 h), the cumulative release amount of DTX were ~84.9%, which is about six times higher than that at pH 7.4. The prepared novel p123-DTX conjugates may offer a great benefit for drug delivery and controlling the drug release.Keywords:docetaxel;conjugates;nano-micelles;stability;pH controlled release

研究领域: 药剂学 · 生物材料学
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Polymer Chemistry · 2015 ·Vol. 7 ·期 4 ·899-904 · IF 5.52

Synthesis of photoresponsive polymeric propesticide micelles based on PEG for the controlled release of a herbicide

Kaikai Ding,Liyan Shi,Ling Zhang,Tian Zeng,Yihua Yin,Ying Yi

A novel amphiphilic polymer–pesticide conjugate was synthesized by conjugation of PEG with the photolabile o-nitrobenzyl group followed by grafting dichlorophenoxyacetic acid (2,4-D), which can self-assemble into photoresponsive micelles in aqueous solutions for a controlled release of the herbicide. 1H NMR and FT-IR confirmed the structure of the synthesized conjugate. TEM observations showed that the micelles had a core–shell configuration. DLS and TEM measurements showed that the average diameters of the micelles decreased by about 40 nm after 365 nm UV irradiation. 1H NMR and UV-Vis studies confirmed that the photoresponse may be ascribed to the photolytic cleavage of o-nitrobenzyl as the connecting arm in the polymeric chain. No release of the micelles was detected without light, while the cumulative release rate from the micelles increased gradually upon solar-simulating radiation, reaching 99.6% in 8 h.

研究领域: 材料科学 · 农业科学 · 高分子化学
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JOURNAL OF APPLIED POLYMER SCIENCE · 2016 ·Vol. 133 ·期 18 · IF 1.866

Synthesis, characterization, and cytotoxicity of star-shaped polyester-based elastomers as controlled release systems for proteins

Fangyuan Guo,Wei Zhang,Xiaohong Pei,Xia Shen,Qinying Yan,Weiyong Hong,Gensheng Yang

With the growing number of therapeutic proteins on the market, effective delivery systems are receiving particular attention. In this study, biodegradable elastomers, intended for protein drug delivery and based on methacrylic tripoly(ε-caprolactone- co - d , l -lactide) cyclic ester with different ratios of ɛ-caprolactone to d , l -lactide and methacrylic bipoly[ɛ-caprolactone- b -poly(ethylene glycol)- b -ɛ-caprolactone], were synthesized and characterized. The degradation behavior, bovine serum albumin (BSA)-releasing kinetics, and cytotoxicity of the elastomers in vitro were investigated. The elastomers were degraded by the hydrolysis of the ester bond; this resulted in pH changes, which further affected the degradation rate. The BSA-releasing behavior was strongly dependent on the diffusion mechanism. In the diffusion-controlled period, nearly sustained and stable BSA release was achieved. Furthermore, the elastomers displayed good biocompatibility, as demonstrated by a 3-(4,5-dimethyl thiazol-2-yl)−2,5-diphenyl tetrazolium bromide assay and inflammation–induction experiments, and are considered promising candidates for the controllable delivery of protein drugs. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133 , 43393.

研究领域: 生物材料 · 药剂学 · 生物医学工程
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

10-hydroxycamptothecin-loaded starch-based microcapsules with the stepwise responsive release strategy for targeted controlled release

Qingye Meng,Shuangling Zhong,Jia Wang,Yan Gao,Xuejun Cui

Controlled and accurate drug release at the target site have been the focus of research. Especially in cancer therapy, economical, convenient and accurate delivery strategies could help to reduce the toxic effects of drugs on normal tissues and improve drug availability. In the study, glutathione (GSH)-responsive microcapsules (FA-RSMCs) were prepared by sonochemical method based on thiolated modified starch . 10-Hydroxycamptothecin (HCPT) was designed as a reactive oxygen species (ROS)-responsive polyprodrug (polyHCPT), which was loaded into the core of the microcapsules to obtain stepwise released drug delivery carriers. In the tumor microenvironment, FA-RSMCs first triggered GSH-responsive cleavage to release polyHCPT, followed by ROS-responsive cleavage of polyHCPT to release intact HCPT drug molecules. The results of experiments in simulated tumor microenvironment showed that FA-RSMCs exhibited good cascade-response release properties in vitro . It exhibited good anti-tumor ability and protection of normal cells in cytotoxicity in vitro . This strategy enhanced the accuracy and safety of targeted delivery of HCPT via microcapsules, which has potential for clinical application.

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Advanced Science · 2023 · IF 15.1

Zinc-Organometallic Framework Vaccine Controlled-Release Zn2+ Regulates Tumor Extracellular Matrix Degradation Potentiate Efficacy of Immunotherapy

Lin Ding,Minli Liang,Yuanyuan Li,Mei Zeng,Meiting Liu,Wei Ma,Fuming Chen,Chenchen Li,Rui L. Reis,Fu-Rong Li,Yanli Wang

Tumor extracellular matrix (ECM) not only forms a physical barrier for T cells infiltration, but also regulates multiple immunosuppressive pathways, which is an important reason for immunotherapy failure. The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway plays a key role in activating CD8 + T cells, maintaining CD8 + T cells stemness and enhancing the antitumor effect. Herein, a zinc-organometallic framework vaccine (ZPM@OVA-CpG) prepared by self-assembly, which achieves site-directed release of Zn 2+ in dendritic cell (DC) lysosomes and tumor microenvironment under acidic conditions, is reported. The vaccine actively targets DC, significantly enhances cGAS-STING signal, promotes DC maturation and antigen cross-presentation, and induces strong activation of CD8 + T cells. Meanwhile, the vaccine reaches the tumor site, releasing Zn 2+ , significantly up-regulates the activity of matrix metalloproteinase-2, degrades various collagen components of tumor ECM, effectively alleviates immune suppression, and significantly enhances the tumor infiltration and killing of CD8 + T cells. ZPM@OVA-CpG vaccine not only solves the problem of low antigen delivery efficiency and weak CD8 + T cells activation ability, but also achieves the degradation of tumor ECM via the vaccine for the first time, providing a promising therapeutic platform for the development of efficient novel tumor vaccines.

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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2023 · IF 5.2

αvβ3 Receptor-targeted acid-responsive controlled-release endosome escape doxorubicin-loaded liposomes for A549/ADR treatment

Hailiang Chen,Chenyu Liu,Simiao Yu,Hengjun Zhou,Farishta Shafiq,Weihong Qiao

The emergence of liposomes has provided a breakthrough for the clinical use of highly toxic chemotherapeutic drugs . However, the clinical effects of conventional drug-loaded liposomes are unsatisfactory due to the lack of specific targeting of cancer cells and the inability to achieve endosome escape and controllable release in vivo. In this paper, a cRGD-PEOz-Hz-DOB (cPzD) molecule with specific targeting, endosomal escape, and endogenous acid-sensitive controlled release ability was creatively designed and synthesized to prepare drug-loaded liposomes cPzDGX encapsulating the anticancer drug Doxorubicin (DOX) in order to enhance the anticancer performance of DOX. The study found that the hydrazone bond in cPzD reached a breakage rate of 42% within 48 h at pH 5.0, so the cumulative release rate of cPzDGX at pH 5.0 for 48 h was as high as 82.9%, which was 22.5% higher than that at pH 7.4. Moreover, the uptake of cPzDGX in A549/ADR cells was increased by 62% at 2 h, and the expression of the green fluorescent protein gene EGFP was also increased by 36% relative to the targeting control group, indicating that cRGD modification could effectively improve the targeting ability of liposomes to cancer cells. In addition, it was demonstrated that PEOz modification could help drug carriers achieve endosome escape because the green fluorescent protein expression in the PEOz-modified liposome group was 60.5% higher than that in the PEG-modified group. Finally, the cell viability of the cPzDGX group decreased by 17.2% relative to the free DOX group when the DOX concentration was 1 μg/mL in the cytotoxicity assay, and the diameter reduction of 3D tumor MCs increased by 34.4%. And cPzDGX could effectively enhance the permeability of free DOX to solid tumors. The above results indicate that the DOX-loaded liposomes cPzDGX we designed have great prospects for the accurate and efficient treatment of cancer.

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