COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Tingsheng Yan,Dalong Li,Jiwei Li,Feng Cheng,Jinju Cheng,Yudong Huang,Jinmei He
A glycyrrhetinic acid-modified chitosan-cystamine-poly(ε-caprolactone) copolymer (PCL-SS-CTS-GA) micelle was developed for the co-delivery of doxorubicin (DOX) and curcumin (CCM) to hepatoma cells. Glycyrrhetinic acid (GA) was used as a targeting unit to ensure specific delivery. Co-encapsulation of DOX and CCM was facilitated by the incorporation of poly(ε-caprolactone) (PCL) groups. The highest drug loading content was 19.8% and 8.9% (w/w) for DOX and CCM, respectively. The PCL-SS-CTS-GA micelle presented a spherical or ellipsoidal geometry with a mean diameter of approximately 110 nm. The surface charge of the micelle changed from negative to positive, when the pH value of the solution decreased from 7.4 to 6.8. Meanwhile, it also exhibited a character of redox-responsive drug release and GA/pH-mediated endocytosis in vitro . In simulated body fluid with 10 mM glutathione, the release rate in 12 h was 80.6% and 67.2% for DOX and CCM, respectively. The cell uptake of micelles was significantly higher at pH 6.8 than pH 7.4. The combined administration of DOX and CCM was facilitated by PCL-SS-CTS-GA micelle. Results showed that there was strong synergic effect between the two drugs. The PCL-SS-CTS-GA micelle might turn into a promising and effective carrier for improved combination chemotherapy.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2018
·
IF 5.667
Chang Wei,Xia Dong,Yan Zhang,Jie Liang,Afeng Yang,Dunwan Zhu,Tianjun Liu,Deling Kong,Feng Lv
Multispectral fluorescence imaging, from cellular imaging to in vivo imaging, represents a significant advancement for drug delivery research. Tracking multi-drug release using real-time imaging in vivo can reveal the release processes for guiding the design of an ideal drug delivery system to implement combination chemotherapy. Herein, a sustained and programmed drug delivery system was developed based on a PCL-PEG-PCL thermosensitive hydrogel combined with chitosan-multiwalled carbon nanotubes using doxorubicin (DOX) and rhodamine B (RB) as the model drugs. Dual drug delivery was monitored by fluorescence imaging at the cellular level, and in vivo fluorescence signals in nude mice were tracked by a multispectral fluorescence imaging system. The results demonstrated that the release of these two drugs can be dynamically tracked in vitro and in vivo, respectively using fluorescence imaging techniques. After loading onto carbon nanotubes, DOX exerted a significantly slower release rate compared with RB in the hydrogel due to the dual release of DOX. The hydrogel-carbon nanotube delivery system achieved programmed release of DOX and RB, which affirmed that it can be a potential drug delivery system with programmed release for combined administration.
研究领域:
生物医学工程
·
药理学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Advances
·
2023
·
IF 0
Yiqing Liu,Peiyong Guo,Xinhao Dong,Yina Xu,Dan Li,Hua Zheng,Jianhong Liao
Here, we combined reversible addition-fragmentation chain transfer (RAFT) polymerization and amide coupling reaction to develop a novel drug-polymer conjugate using poly(AMA- co -IMMA)-b-poly(OEGMA) (termed as PAIPO) as nanocarriers. In order to enhance cellular uptake and obtain subsequent endo/lysosomal escape capacity, the dual-drugs-conjugated prodrug was then coupled with 2,3-dimethylmaleimide (DA) moieties and implanted with imidazolyl groups, respectively. Paclitaxel (PTX) was conjugated to PAIPO via 3,3′-dithiodipropionic acid (DPA) to construct a GSH-responsive moiety, while doxorubicin (DOX) was conjugated to PAIPO via 4-formyl benzoic acid to construct a pH-responsive moiety, which synergistically enabled a synchronized and precise drug delivery. The micelles self-assembled from DOX/ [email protected] DA showed an ideal average diameter (163.2–178.3 nm), contributing to passive targeting by the EPR effect. Moreover, a switch of the surface Zeta potential of micelles from steady negatively charged (− 9.74 ± 0.54 mV) at pH 7.4 to positively charged (+ 6.33 ± 1.25 mV) at pH 6.5, facilitated the long blood circulation and cellular endocytosis of micelles, respectively. More importantly, in vitro studies confirmed that DA M(DOX n /PTX) exhibited a strong synergism against tumor cells, and under slightly acidic conditions (pH 6.5), the combination index (CI) values for DA M(DOX 1 /PTX) on HeLa and Skov-3 cells were estimated to be 0.47 and 0.49 (previous to be 0.50 and 0.56 at pH 7.4), respectively. And in vivo results showed effective tumor accumulation potential, remarkable biosafety, and biocompatibility. Combined, such synchronized delivery approach based on multi-responsive micelles might potentiate the efficacy of combination chemotherapy in clinical cancer treatment.
研究领域:
药物递送系统
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肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Xinfeng Cheng,Yong Jin,Tongbing Sun,Rui Qi,Hanping Li,Wuhou Fan
A novel pH and oxidation dual-responsive and injectable supramolecular hydrogel was developed, which was formed from multi-block copolymer poly(ether urethane) (PEU) and α-cyclodextrin (α-CD) inclusion complexes (ICs). The PEU copolymer was synthesized through a simple one-pot condensation polymerization of poly(ethylene glycol), di(1-hydroxyethylene) diselenide, dimethylolpropionic acid and 3-isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate. In aqueous solution, the amphiphilic PEU copolymers could self-assemble into nanoparticles with dual pH and oxidation sensitivities, which can efficiently load and controllably release a hydrophobic drug indomethacin (IND). Then a dual-drug loaded supramolecular hydrogel was obtained by addition of α-CD and hydrophilic model drug (rhodamine B, RB) into the resulting IND-loaded PEU nanoparticle solution. The rheology studies showed that the supramolecular hydrogels with good injectability underwent a pH-induced reversible sol–gel transition and an oxidation-triggered degradation behavior. The in vitro drug release results demonstrated that the hydrogels showed dual drug release behavior and the release rates could be significantly accelerated by addition of an oxidizing agent (H 2 O 2 ) or increasing the environmental pH. Therefore, this injectable and dual stimuli-responsive supramolecular hydrogel based codelivery systems could potentially be a promising candidate for controlled drug delivery systems.
研究领域:
药剂学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science China-Chemistry
·
2021
·Vol. 64
·期 6
·1020-1030
·
IF 9.445
Tu Yalan,Zheng Rui,Yu Fangzhou,Xiao Xuan,Jiang Maoling,Yuan Youyong
Determination of whether multidrug nanocarriers can deliver and release loaded drugs at a predefined synergistic ratio to target cancer cells is crucial. Although there are many successful applications for delivery of multiple drugs, most current carriers are unable to achieve coordinated loading and release, leading to a drug release ratio that disagrees with the predefined loading ratio. In this work, a simple dual-drug delivery system with a flexible and controllable drug release ratio was constructed to deliver two anticancer drugs, doxorubicin (DOX) and curcumin (CUR). The drug ratio of DOX and CUR can be easily tuned for an enhanced synergistic effect, and the drugs can be released at predesigned ratios due to synchronous drug activation and nanoparticle collapse. Drug release at predefined ratios for synergistic anticancer therapy was demonstrated via in vitro and in vivo experiments. Therefore, the dual drug delivery system developed here provides a simple and efficient strategy for combination chemotherapy.
研究领域:
肿瘤学
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药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Fen Ao,Changyu Yin,Xiaomin Luo,Wen Shen,Xuemei Ge,Yan Zheng
Skin wound repair is a complex dynamic process. Current dual-drug delivery systems struggle to adapt to the process of wound healing. Therefore, the construction of a dual-drug delivery system with intelligent responsiveness, controllable release, and understanding the repair mechanisms, is a current research challenge. This study described the design of a new gelatin-based dual-drug delivery system (PGDMD) using electric field stimulation to achieve a controlled drug release. In vitro drug release experiments demonstrated PGDMD completed the transition from a fiber membrane state to a gel state during the release process. Quercetin released with a rapid release within the first 60 min and amikacin released over 24 h. The amount of drug released in the same release time was increased mainly through electrostatic action under the effect of the electric field and accelerated the movement of drug molecules. The non-targeted metabolomics analysis revealed that PGDMD mainly reduced inflammation and oxidative stress responses by upregulating the expression of antioxidant-related metabolites, thereby improving the therapeutic effect of rat traumatic skin. In conclusion, the dual-drug delivery system might be potentially applied to high-performance medical devices, pharmaceuticals and other industry products, and provides research ideas and reference for exploring the interaction between biomaterials and the organism.
研究领域:
生物材料学
·
药剂学
·
医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Enyang Yao,Yang Li,Kai Deng,Wei He,Milad Ashrafizadeh,João Conde,Liyu Yang
Osteosarcoma is the most common primary bone tumor with a high metastatic rate. Despite the improvement in patient prognosis with conventional therapeutics, enhancing the survival of patients with metastatic disease remains a challenge. Zoledronic acid (ZOL) stimulates apoptosis in cancer cells and is considered a promising drug for osteosarcoma therapy. Moreover, depletion of Inhibin Subunit Beta A (INHBA), a member of the transforming growth factor superfamily, can suppress osteosarcoma cell proliferation and invasion. Regarding the restricted potential of monotherapy, combination therapies, such as small interfering RNA (siRNA) and chemotherapy, are ideal strategies. However, off-target effects and adverse impacts lead to unsatisfactory clinical efficacy of these drugs. To address this challenge, we designed a folic acid-modified macrophage membrane coated with a carbon quantum dot (CQD) nanoplatform for the co-delivery of ZOL and siINHBA (ZOL-siINHBA@CQD@RM-FA). The anticancer activity of this nanotherapeutic agent was examined in vitro and in vivo . ZOL-siINHBA@CQD@RM-FA was approximately 200.7 nm in size, had a negative charge, excellent pH responsiveness, desirable biocompatibility, and high cellular uptake. This nanosystem achieved favorable co-delivery of ZOL/siINHBA and impaired osteosarcoma proliferation and invasion in vitro . Notably, intravenous administration facilitated tumor growth regression and inhibited lung metastasis without systemic toxicity. Accordingly, this nanotherapy could be considered an effective treatment for osteosarcoma, and the nanodelivery system shows potential for combined therapy by co-delivering genes and chemotherapy drugs.
研究领域:
肿瘤学
·
纳米医学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2023
·
IF 5.8
Qianqian Zhang,Xiaojun Zhou,Haibo Du,Yujie Ha,Yao Xu,Rongguang Ao,Chuanglong He
The clinical treatment of infectious bone defects is difficult and time-consuming due to the coexistence of infection and bone defects, and the simultaneous control of infection and repair of bone defects is considered a promising therapy. In this study, a dual-drug delivery scaffold system was fabricated by the combination of a three-dimensional (3D) printed scaffold with hydrogel for infected bone defects repair. The 3D printed polycaprolactone scaffold was incorporated with biodegradable mesoporous silica nanoparticles containing the small molecular drug fingolimod (FTY720) to provide structural support and promote angiogenesis and osteogenesis. The vancomycin (Van)-loaded hydrogel was prepared from aldehyde hyaluronic acid (AHA) and carboxymethyl chitosan (NOCC) by the Schiff base reaction, which can fill the pores of the 3D-printed scaffold to produce a bifunctional composite scaffold. The in vitro results demonstrated that the composite scaffold had Van concentration-dependent antimicrobial properties. Furthermore, the FTY720-loaded composite scaffold demonstrated excellent biocompatibility, vascularization, and osteogenic ability in vitro. In the rat femoral defect model with bacterial infection, the dual-drug composite scaffold showed a better outcome in both infection control and bone regeneration compared to other groups. Therefore, the prepared bifunctional composite scaffold has potential application in the treatment of infected bone defects.
研究领域:
生物材料学
·
组织工程学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
·
IF 2.5
Lin Zhan,Xuelian Yin,Li Qiu,Chenchen Li,Yanli Wang
The nanomedicine system based on dual drug delivery systems (DDDs) can significantly enhance the efficacy of tumor treatment. Herein, a metal-organic framework, Zeolite imidazole salt frames 8 (ZIF-8), was successfully utilized as a carrier to load the dual chemotherapeutic drugs doxorubicin (DOX) and camptothecin (CPT), named DOX/CPT@ZIF-8 (denoted as DCZ), and their inhibitory effects on 4T1 breast cancer cells were evaluated. The study experimentally demonstrated the synergistic effects of the dual chemotherapeutic drugs within the ZIF-8 carrier and showed that the ZIF-8 nano-carrier loaded with the dual drugs exhibited stronger cytotoxicity and inhibitory effects on 4T1 breast cancer cells compared to single-drug treatment. The use of a ZIF-8-based dual chemotherapeutic drug carrier system highlighted its potential advantages in suppressing 4T1 breast cancer cells.
研究领域:
纳米医学
·
肿瘤学
·
药物递送
✓ 已验证
DOI
PubMed
高影响因子
Advanced Intelligent Systems
·
2024
·
IF 6.8
Yukun Zhong,Haining Li,Teng Jiang,Xueliang Mu,Munetoshi Seki,U Kei Cheang
Magnetic microrobots have the potential for anti-cancer drug delivery; however, using dual-drug to counter drug resistance, a critical issue in cancer research, has only been briefly investigated. This study introduces the double-layered metal-organic-frameworks (MOFs)-based microswimmers for sustained dual-drug delivery. These microswimmers are made up of ZIF-8 and MIL-100, biocompatible MOFs, that can selectively adsorb two types of drugs. The MOFs increase the surface area of the microswimmers by ≈2.42 times, which greatly enhances drug adsorption, and improves hydrophilicity, which reduces adhesion for surface locomotion. Their biocompatibility and dual-drug adsorption are verified through cell viability and drug-loading tests. The microswimmers have remarkable versatility in loading different drug combinations (DHA + 5-FU, CPT-11, or DOX), indicating the potential for adaptive therapy. They can inhibit cancer cells for up to 72 h through the sustained release of dual drugs. In contrast, drug treatments without microswimmers only inhibit cell proliferation for 24 h, leading to a significant rebound. This study provides a method to mass fabricate fully biocompatible microrobots with dual drug loading versatility and high drug adsorption capacity; thus, suggests a powerful platform for sustained adaptive dual-drug therapy.
研究领域:
生物医学工程
·
药物递送系统
·
癌症研究
✓ 已验证
产品关联
DOI
高影响因子
POLYMER INTERNATIONAL
·
2020
·Vol. 69
·期 7
·619-626
·
IF 2.574
Liping Yin,Yanli Bao,Lin Liu,Jinze Wang,Li Chen
In clinical treatment, multidrug resistance (MDR) is one of the major obstacles resulting in the failure of chemotherapy. It is still a challenge to overcome MDR. Herein, we fabricated intelligent dextran-based dual-drug delivery systems histidine modified dextran conjugated doxorubicin/zinc porphyrin/paclitaxel (DHTD/Zn-TPP/PTX) via supramolecular metallo-coordination for synergistic chemo-photodynamic therapy to overcome cancer drug resistance. In this designed DHTD/Zn-TPP/PTX, one anticancer drug (doxorubicin, DOX) was conjugated on the dextran backbone through a reactive oxygen species sensitive linker and the other drug PTX was encapsulated into the acid responsive supramolecular micelles formed by the photosensitizer Zn-TPP and histidine grafted on dextran. DHTD/Zn-TPP/PTX with excellent stability could be effectively internalized by tumour cells. In the acidic tumour environment, the loaded PTX and Zn-TPP as photosensitizer could be released; moreover, when irradiated with light the conjugated DOX could be specifically released because the linker broke. As the obtained data indicate, DHTD/Zn-TPP/PTX exhibited not only an enhanced anticancer therapeutic effect but also significant growth inhibition for drug-resistant MCF-7/ADR cells to reverse MDR, having great potential for synergistic treatments of cancer to overcome MDR. © 2020 Society of Chemical Industry
研究领域:
肿瘤学
·
药物递送
·
生物材料
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2024
·
IF 4.4
Shixin Li,Bing Yang,Liang Ye,Shuqi Hu,Benhong Li,Yanjun Yang,Yichuan Hu,Xiaobin Jia,Liang Feng,Zhiwei Xiong
The integration of multiple therapeutic agents within a single nano-drug carrier holds promise for advancing anti-tumor therapies, despite challenges posed by their diverse physicochemical properties. This study introduces a novel multi-stage microfluidic co-encapsulation platform designed to address these challenges. By carefully orchestrating the nano-precipitation process sequence, this platform achieves sequential encapsulation of two drugs with markedly different physicochemical characteristics. Using the multi-stage microfluidic TrH chip, hybrid nanoparticles (HNPs) loaded with paclitaxel (PTX)-simvastatin (SV), PTX-lenvatinib (LV), and SV-LV were synthesized. Unlike conventional Bulk methods and existing commercial microfluidic Tesla and Baffle chips, the HNPs produced here exhibit a core–shell structure and uniform particle size distribution, crucial for enhancing drug delivery efficacy. Notably, this method achieves nearly 100 % encapsulation efficiency for both drugs across a dual-drug feed ratio range from 1:4 to 4:1. Drug loading efficiencies were quantified for PTX-SV/HNPs (14.97 ± 1.19 %), PTX-LV/HNPs (16.58 ± 0.69 %), and SV-LV/HNPs (19.21 ± 2.38 %). PTX-SV/HNPs demonstrated sequential release characteristics of SV and PTX, as confirmed by in vitro drug release experiments. Significantly, PTX-SV/HNPs exhibited superior cytotoxicity against HepG2 cells compared to individual PTX and SV treatments, underscoring their potential in cancer therapy. In conclusion, the developed multi-stage microfluidic platform represents a robust strategy for co-encapsulating drugs with substantial physicochemical disparities, thereby offering a promising avenue for advancing multi-drug delivery in nanomedicine applications.
研究领域:
药剂学
·
纳米医学
·
肿瘤治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）