INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2018
·
IF 3.862
Yawei Du,Longbing Ling,Muhammad Ismail,Wei He,Qing Xia,Wenya Zhou,Chen Yao,Xinsong Li
Camptothecin (CPT) is an important topoisomerase I enzyme ( Topo I) targeting anti-cancer drug, but its oral administration is limited by poor bioavailability and severe side effects. In this study, a redox sensitive CPT prodrug loaded solid lipid nanoparticles (SLN) system for oral delivery was developed. First of all, CPT-palmitic acid conjugate via a cleavable disulfide bond linker (CPT-SS-PA) was synthesized and encapsulated into SLN. The drug release of SLN was evaluated in neutral environment, simulated gastrointestinal fluid and reductive solution. The results indicated that CPT-SS-PA SLN maintained chemical structural stability in simulated physiological environment but exhibited quick reduction-response release of CPT in the presence of dithiothreitol . Furthermore, in vitro cytotoxicity of CPT-SS-PA SLN was tested against cancer cell lines, and the cellular uptake behavior for oral delivery was checked by confocal laser scanning microscopy (CLSM) using Caco-2 cells model. From the data, CPT-SS-PA SLN revealed high anti-cancer activity and enhanced Caco-2 cell absorption. Finally, the oral bioavailability and intestinal safety of CPT-SS-PA SLN were preliminary evaluated by in vivo pharmacokinetic and histopathological study, respectively. This study demonstrated that CPT-SS-PA SLN could be developed as an effective CPT oral delivery system due to its enhanced oral bioavailability and reduced intestinal side effect.
研究领域:
药学
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纳米技术
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药物递送系统
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癌症研究
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DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2022
·
IF 9.965
Tianyu Gao,Hongxin Liu,Zhigang Xie,Min Zheng
Design of nanovectors inspired by nature is a short cut to improve the efficacy and bioavailability of chemotherapeutic agents, while reduce the toxicity. In this work, strongly hydrophobic camptothecin (CPT) was modified with different chain length of fatty acid (C4, C9 and C18) to synthesize CPT4C, CPT9C and CPT18C, respectively. CPT4C, CPT9C and CPT18C could complex with human serum albumin (HSA) readily to prepare CPT4C-HSA, CPT9C-HSA and CPT18C-HSA nanoagents. In vitro MTT assays demonstrated CPT18C-HSA possessed the highest cell killing capacity, due to the elevated cellular uptake that resulted from albumin-mediated transportation. In vivo tumor inhibition experiments verified that CPT18C-HSA had the most remarkable antitumor efficiency with distinctly lowered physiological toxicity. It could be used in large doses without obvious side effects. We believe this albumin-mediated transportation mode has great potential for efficient delivery of hydrophobic and/or physiologically unstable drugs.
研究领域:
药学
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纳米技术
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生物医学工程
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肿瘤学
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DOI
PubMed
高影响因子
PHARMACEUTICAL CHEMISTRY JOURNAL
·
2017
·Vol. 51
·期 6
·491-493
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IF 0.445
Zhu Jian,Jin Zhi-Min
Insoluble camptothecin was converted into the corresponding hydrosoluble analog, camptothecin carboxylate, by using 1,1,3,3-tetramethylguanidine as hydrolyzing agent. The ethanol/K 2 CO 3 /H 2 O aqueous two-phase system was established to extract the hydrosoluble camptothecin carboxylate. Through two-stage extraction from crude camptothecin of 5.4%, purity, final hydrosoluble camptothecin was obtained with a purity of 98.5% at a total yield of 78.4%.
研究领域:
药物化学
·
分离工程
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产品关联
DOI
高影响因子
Bosnian Journal of Basic Medical Sciences
·
2022
·
IF 3.759
Zhaopei Guo,Zian Wang,Ruifeng Liang,Huayu Tian,Xuesi Chen,Meiwan Chen
Camptothecin (CPT) has attracted much attention due to its potent antitumor activities. However, the undesirable physicochemical properties, including poor water solubility, unstable lactone ring, and severe adverse effects, limit its further application. In this study, two water-soluble prodrugs, CPT-lysine and CPT-arginine, were designed and synthesized by conjugating lysine or arginine with CPT, improving its solubility, pharmacokinetic properties, and tumor penetration. Importantly, the introduction of arginine into CPTR contributed to the mitochondria-specific delivery, which increased mitochondrial reactive oxygen species generation, induced mitochondria dysfunction, and enhanced cell apoptosis and in vivo anti-cancer effect. This strategy is believed to hold great potential for organelle-specific synergistic anti-tumor therapy.
研究领域:
肿瘤学
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药物化学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Qiao Qiao,Jie Li,Chunying Tao,Meiyang Yang,Weijun Chen,Lipeng Qiu,Huiming Tu
Studies have shown that inflammation is closely linked to the cancer development, and the patients with inflammatory bowel disease (IBD) have a higher risk of colon cancer. Celecoxib (CXB) and camptothecin (CPT) showed potential treatment for IBD and colon cancers, respectively. However, their applications are limited by synchronous delivery, water insolubility, and off-target side effects. Herein, a glutathione (GSH) responsive chondroitin sulfate A (CSA)-SS-CXB micelle loaded with CPT (CSA-SS-CXB@CPT) was prepared as a targeted system to treat colon cancer by anti-inflammatory and antitumor synergistic effect. Specifically, CSA had tumor tumor-targeting effect due to colon cancer lesion-high expression of CD44 receptors. In vitro results verified that CSA-SS-CXB@CPT selectively internalized into colon cancer HT-29 cells and had strong reactive oxygen species (ROS) elimination ability. The CSA-SS-CXB@CPT could rapidly release CXB and CPT in the tumor microenvironment for playing an anti-tumor role. In vivo experiments illustrated that CSA-SS-CXB@CPT significantly targeted tumor tissues and suppressed tumor growth without producing serious side effects in tumor-bearing nude mice. Therefore, this work provides an opportunity for targeted co-delivery of anti-inflammatory and chemotherapy drugs to treat colon cancer.
研究领域:
药学
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肿瘤学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2025
·
IF 4.7
Min Hong,Haobin Chen,Lei Li,Xiaoyan Liu,Qinghong Ji,Shuang Cheng,Chenzhong Li
A glutathione (GSH)-responsive amphiphilic camptothecin (CPT) prodrug, Lc-ss-CPT, was synthesized by conjugating hydrophobic CPT with hydrophilic L-carnitine (Lc) via a disulfide carbonate linker. The prodrug self-assembled into spherical nanoparticles (Lc-ss-CPT NPs, hydrodynamic diameter: ∼180 nm). In simulated gastrointestinal fluids and FBS-containing PBS, the NPs maintained stability over 24 h, with <10 % CPT leakage after 8 h. In vitro transcytosis studies using Caco-2 monolayers revealed an 188.5-fold higher apparent permeability coefficient for Lc-ss-CPT NPs than free CPT. The confocal fluorescence imaging studies demonstrated that the specific affinity between L-carnitine and organic cation transporter 2 (OCTN2) enhanced intestinal absorption of Lc-ss-CPT NPs and then transported into the bloodstream through transcytosis, facilitated by the Golgi apparatus and endoplasmic reticulum, enabling tumor accumulation. Pharmacokinetic analysis in rats showed oral administration of Lc-ss-CPT NPs achieved a higher bioavailability of 49.6 %. In HCT-116 cells, Lc-ss-CPT NPs reduced intracellular GSH to 5.4 % of baseline at 6 h, elevated ROS levels by 4.2-fold, and induced 71.2 % apoptosis. In MC38 tumor-bearing mice, oral Lc-ss-CPT NPs suppressed tumor growth by 86 % (vs. 12 % for free CPT). These data demonstrate the potential of Lc-ss-CPT NPs as an orally administrable platform for targeted CPT delivery.
研究领域:
药理学
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肿瘤学
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纳米医学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2019
·
IF 7.901
Ying Qu,Bingyang Chu,Xiawei Wei,Minyi Lei,Danrong Hu,Ruoyu Zha,Lin Zhong,Mengyao Wang,Fangfang Wang,Zhiyong Qian
At present, chemotherapy remains to be one of the most important therapeutic approaches for malignant tumors. The tumor microenvironment(TME)-responsive intelligent drug delivery systems are still the hot research topics in delivering chemotherapeutic drugs. Camptothecin (CPT) possesses very strong antitumor activities , but its clinical application is hindered by its poor water-solubility and serious toxic side effects. Herein, a new intelligent and TME-responsive P(CPT-MAA) prodrug nanogel was developed for delivering CPT and reducing its side effects. P(CPT-MAA) prodrug nanogels were prepared with methacrylic acid (MAA), CPT monomer (CPTM) and N , N ′-methylenebisacrylamide (Bis) via distillation-precipitation polymerization, in which CPT was covalently conjugated into the nanogels via redox-responsive disulfide linker. The as-prepared nanogels were spherical shapes with uniform size and narrow size distribution. With the help of redox-responsive property of disulfide linker and pH-responsive property of PMAA, the release of CPT from prodrug nanogels was redox/pH-dual dependent and could be accelerated by the increased concentration of GSH and the decreased pH value, which were favorable to realize the “on-demand” drug release in tumor cell and tumor tissue microenvironment. Furthermore, P(CPT-MAA) prodrug nanogels exhibited superior antitumor activity both in vitro and in vivo without observed side effects. Hence, the prepared P(CPT-MAA) prodrug nanogels may be a promise delivery system for chemotherapeutic agents.
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
高影响因子
PHYTOMEDICINE
·
2016
·
IF 2.937
Qin Tang,Fangling Ji,Wenhui Sun,Jingyun Wang,Jianli Guo,Lianying Guo,Yachen Li,Yongming Bao
Background 10-Hydroxy camptothecin (HCPT), a naturally occurring alkaloid, is a clinical drug for cancer chemotherapy . Baicalein (BA) is a flavonoid extracted from the root of Scutellaria baicalensis . The synergistic anti-cancer effect of BA and HCPT has not been reported. Purpose To explore whether and how BA enhances the anti-cancer effect of HCPT in BGC823 cells. Methods Cell viability was measured by MTT assay. Apoptosis and cell cycle were analyzed through flow cytometry and western blotting analysis. DNA damage was determined by a comet assay . The activity of topoisomerase I (Topo I) was detected by the plasmid DNA relaxation assay. The synergistic anti-cancer effect of BA and HCPT in vivo was tested by BGC823 xenografted tumor model. Results BA at non-toxic doses prominently enhanced the anti-cancer activities of HCPT in BGC823, MCF7 and SMMC7721 cells. Combination treatment of BA and HCPT induced BGC823 cells apoptosis mainly via intrinsic rather than extrinsic pathways, and preferentially arresting cell cycle in G1 and G2 phases with the aid of p21 . Of note, p53, the upstream regulator of cell apoptosis and cycle, was increased by 5 folds in combination group. It helped to further trigger DNA damage and inhibit Topo I catalytic activity after combination treatment of BA and HCPT. Moreover, the BGC823 xenografted tumor growth rate in nude mice was repressed in a greater degree ( P < 0.01) in the combinational group than the single-drug group. Conclusion HCPT and BA, a new and effective combination therapy, synergistically target Topo I and up-regulate p53 to induce cell apoptosis and cell cycle arrest.
研究领域:
肿瘤学
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药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2020
·
IF 3.693
Zhang Zhi-Jun,Shang Xiao-Fei,Yang Liu,Shi Yan-Bin,Liu Ying-Qian,Li Jun-Cai,Yang Guan-Zhou,Yang Cheng-Jie
As a famous quinoline alkaloid, camptothecin (CPT) presented the significant anti-tumor activity, as well as the interesting insecticidal activities, but the low solubility, poor hydrophobicity and cuticular penetration of CPT have been severely limited the field application. In this study, we conjugated the camptothecin with polyethylene glycol, forming amphiphilic copolymer, mPEG-CPT, which could be self-assembled into micelles, or formed a hydrogel with α-CD by super-cross-linking to combine delivery with acetamiprid or nitenpyram. Results showed that the nitenpyram or acetamiprid loaded hydrogels showed dual phase release behavior, while the micelles displayed a synchronous and fast release profile. Moreover, these four nanopesticides showed potent or superior insecticidal activities and a synergetic effect against Brevicoryne brassicae, Tetranychus cinnabarinus, and Bursaphelenchus xylophilus. This finding indicated that micelles and hydrogels could be used as effective carriers for pesticide combination control.
研究领域:
药剂学
·
农药科学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 10
·2127-2136
·
IF 4.726
Wei Zhang,Xiaoyan Zhou,Tao Liu,Dong Ma,Wei Xue
The co-delivery of multiple drugs has become the primary strategy in cancer therapy in recent years, because this technique could promote synergistic actions, reduce side effects and deter the development of drug resistance. To achieve a controlled and sustained release of the loaded drugs, a supramolecular hydrogel based on the host–guest interactions between a hyperbranched polyglycerol derivative and α-cyclodextrin was prepared and used to co-load camptothecin and doxorubicin for sustainedly synergistic tumor therapy. The gelation kinetics, hydrogel strength and supramolecular structure of the obtained hydrogel were studied by dynamic and steady rheometry under various concentrations of α-CD. The sustained dual drug release from the supramolecular hydrogel in vitro, and their synergistic effect in vitro and in vivo were also explored. Moreover, the supramolecular hydrogel showed receivable blood compatibility and non-cytotoxicity by in vitro and in vivo assays. Therefore, this supramolecular hydrogel could potentially be applied in sustainedly synergistic tumor therapy.
研究领域:
药剂学
·
肿瘤学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2013
·
IF 3.554
Yan-Ling Luo,Xiao-Li Yang,Feng Xu,Ya-Shao Chen,Bin Zhang
Two kinds of thermo-sensitive poly(N-isoproplacrylamide) (PNIPAM) block copolymers, AB 4 four-armed star multiblock and linear triblock copolymers, were synthesized by ATRP with hydroxyl-terminated polybutadiene (HTPB) as central blocks, and characterization was performed by 1 H NMR, FT-IR and SEC . The multiblock copolymers could spontaneously assemble into more regular spherical core–shell nanoscale micelles than the linear triblock copolymer. The physicochemical properties were detected by a surface tension technique, nano particle analyzer, TEM, DLS and UV–vis measurements. The multiblock copolymer micelles had lower critical micelle concentration than the linear counterpart, TEM size from 100 to 120 nm and the hydrodynamic diameters below 150 nm. The micelles exhibited thermo-dependent size change, with low critical solution temperature about 33–35 °C. The characteristic parameters were affected by the composition ratios, length of PNIPAM blocks and molecular architectures. The camptothecin release demonstrated that the drug release was thermo-responsive, accompanied by the temperature-induced structural changes of the micelles. MTT assays were performed to evaluate the biocompatibility or cytotoxicity of the prepared copolymer micelles.
研究领域:
高分子化学
·
药物传递系统
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Plant Science
·
2022
·
IF 6.627
Qiao Chong,Chen Fei,Liu Zhan,Huang Tianfang,Li Wei,Zhang Guolin,Luo Yinggang
Tryptophan decarboxylases (TDCs) are a group of pyridoxal 5′-phosphate-dependent enzymes involved in the enzymatic conversion of tryptophan into tryptamine, a critical biogenic amine. We herein mined and cloned a TDC-encoding gene, CaTDC3, from camptothecin-producing plant Camptotheca acuminata. The intact CaTDC3 was heterologously overexpressed in Escherichia coli and the recombinant CaTDC3 was purified to homogeneity. High-performance liquid chromatography (HPLC)-diode array detector (DAD) and high resolution mass spectrometry (HRMS) data analyses of the CaTDC3-catalyzed reaction mixture confirmed the catalytically decarboxylative activity of CaTDC3. CaTDC3 shows strict stereoselectivity for L-tryptophan. Homology modeling and molecular docking implied CaTDC3’s recognition of L-tryptophan derivatives and analogs. Substrate scope investigations revealed that the appropriate substituent groups on the indole ring, i.e., hydroxylated and halogenated L-tryptophans, could be recognized by CaTDC3 and the decarboxylation reactions generated the corresponding tryptamines. The Cβ -methyl-L-tryptophans were decarboxylated by CaTDC3 efficiently. 1-Thio-L-tryptophan, the NH group of the indole ring replaced by an S atom, could be decarboxylated by CaTDC3. CaTDC3 catalyzed the decarboxylation of 7-aza-L-tryptophan, an N displacement of the C on the aromatic ring, to afford 7-aza-tryptamine. L-Kynurenine, an L-tryptophan degradation product, could be decarboxylated by CaTDC3. The present works uncover a catalytically promiscuous TDC and the TDC is a versatile decarboxylase in synthetic biology for specialized pharmaceutically important substances.
研究领域:
生物化学
·
酶学
·
药理学
·
合成生物学
✓ 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）