RESEARCH ON CHEMICAL INTERMEDIATES
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2012
·Vol. 38
·期 7
·1421-1429
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IF 0.697
Li He-ping,Qin Long,Wang Zhou-dong,Li Shan
In order to improve drug loading and achieve a good release effect, this paper adopts the ramose method, choosing chitosan as the carrier and 5-fluorouracil (5-Fu) as a model drug. Ramose chitosan-lysyl-5-Fu(3) and ramose tetralactosyl-lysyl-chitosan-5-Fu(6) were synthesized successfully, then the in vitro release of (6) was researched. The results show that the drug loading of (3) and (6) are 9.17 and 1.63% (w/w), respectively. The in vitro release behavior of (6) in pH 7.4 phosphate buffer solution and pH 1.2 HCl–KCl solution were studied. The zero order release time that (6) maintains in alkaline and acidic media are 64 and 24 h, and the total release by 184 h are 71.97 and 82.34%, respectively. The performance is smooth throughout the whole stage of release, and the concentration of cumulative release is lower in the alkaline environment than in the acidic environment over the same time.
研究领域:
药剂学
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生物材料学
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产品关联
DOI
高影响因子
CRYSTENGCOMM
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2021
·Vol. 23
·期 46
·8027-8032
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IF 3.545
Fenghua Chen,Jie Fan,Xiuzhi Chen,Yanping Li,Chengfeng Liang,Shizhao Ren,Rongrong Xue
Polymorph control of 5-fluorouracil (5-FU) was achieved by ball milling. Form II was synthesized through one-step neat grinding of raw 5-FU (RFU), and Form III (a new polymorph) was obtained by neat grinding RFU twice. Forms II and III of 5-FU were prepared separately through ball milling with different amounts of ethanol as an additive at the same period without influencing each other.
研究领域:
药物化学
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制药工程
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产品关联
DOI
高影响因子
VIBRATIONAL SPECTROSCOPY
·
2024
·
IF 2.7
Fan Yang,Jing Zhao,Zhengang Wu,Yingna Wei,Hengyong Wei,Jingwu Li,Bo Li
Cocrystal is a new class of pharmaceutical crystal form, which could improve the physical and chemical properties of drug substance without affecting the internal structure of drug substance. Therefore, the cocrystals show a great deal of potential in the development and research of drugs. 5-Fluorouracil (5-FU) is one of the most widely used anti-pyrimidine drugs. However, its solubility is poor and its oral bioavailability is low. In this work, the cocrystal of 5-FU with nicotinamide was prepared by the solvent evaporation method. The cocrystal structure was confirmed by infrared spectroscopy (IR), X-ray diffraction (XRD) and Raman spectroscopy. The X-ray diffraction and infrared spectroscopy presented that there were significantly different peaks between the raw drug and the cocrystal. Raman spectral results also indicated the differences of such cocrystal compared with the raw drug. In addition, TiN-Ag composite SERS substrate was used to study the formation of 5-FU cocrystal drugs and the formation process was dynamically monitored, and the interaction between molecules during the cocrystal reaction was deeply understood. The cocrystal reaction process was tracked, it can be found that the peak intensity of the raw drug and cocrystal changes with the reaction, indicating that the TiN-Ag composite substrate can monitor the cocrystal transformation process.
研究领域:
药学
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分析化学
✓ 已验证
产品关联
DOI
高影响因子
REACTIVE & FUNCTIONAL POLYMERS
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2024
·
IF 4.5
Yaxue Xie,Pingxiong Cai,Huining Xiao,Yuanfeng Pan
In this work, a dual-responsive hydrogel for sustainable release of drug was prepared using chitosan grafted with PBA as substrate to form semi-interpenetrating polymer networks (S-IPN) via free-radical crosslinking polymerization of acrylic acid in the presence of MBAA as a crosslinker and KPS as an initiator as well as Fe 3+ .ions introduced. The results from comprehensive characterization indicated that the as-prepared hydrogel possesses cavity structure with the pores of varying sizes, thus facilitating the accommodation of 5-fluorouracil as a model drug. In addition, the swelling behavior of the hydrogels in different pH buffers and glucose solutions was also investigated. As expected, the prepared hydrogels are pH and glucose responsive due to PAA and phenylboronic acid incorporated into the hydrogel, which enables the slow or sustainable release of drug. Moreover, the release processes were fitted with various kinetic models whereas the release was better described by Korsmeyer-Peppas model or the drug release is mainly governed by the release mechanism of the hydrogel is primarily driven by Fickian diffusion from a mechanical point of view. Hydrogel loaded with drug was found to have good antibacterial effects against E. coli and S. aureus, leading to the potential for various medical-related applications.
研究领域:
材料科学
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药学
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生物医学工程
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产品关联
DOI
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
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2015
·Vol. 132
·期 22
·
IF 1.768
Yong Liu,Jieyi Liang,Shoulian Wei,Ling Liu,Miaochan Liao
The purpose of this study was to fabricate and evaluate nanoparticles based on β-conglycinin (7S) and chitosan (CS) to deliver 5-fluorouracil (5-FU). The nanoparticles were prepared with a self-assembly method. Turbidity measurements performed at 600 nm were used to investigate the formation of the nanoparticles as a function of the pH, 7S-to-CS mass ratio, and total concentration of 7S and CS. The optimum conditions for the preparation of the nanoparticles were a pH of 5.5, a 7S-to-CS mass ratio of 4 : 1, and total concentration of 7S and CS of 9 mg/mL. Under these conditions, the nanoparticles in solution had a high turbidity and good stability. Fourier transform infrared spectroscopy revealed that the nanoparticles were formed mainly through electrostatic interactions between the amine groups ( NH 3 + ) of CS and the carboxyl groups ( COO − ) of 7S. Scanning electron microscopy micrographs and dynamic light scattering analysis showed that the nanoparticles had an approximately spherical morphology with a smooth surface, and the mean particle size was about 120 nm with a narrow size distribution. The release of 5-FU showed an initial burst release followed by a sustained release, and the release was pH-dependent. The release mechanism of 5-FU was Fickian diffusion according to the Ritger–Peppas model. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132 , 41963.
研究领域:
药剂学
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生物材料学
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药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2017
·
IF 0
Li Sun,Yunna Chen,Yali Zhou,Dongdong Guo,Yufan Fan,Fangyan Guo,Yufeng Zheng,Weidong Chen
The sustained-release properties of the biodegradable nano-drug delivery systems were used to improve the residence time of the chemotherapeutic agent in the body. These drug delivery systems were widely used to deliver chemotherapeutic drugs. The 5-fluorouracil loaded chitosan nanoparticles prepared in this paper have the above advantage. Here, we found that when the mass ratio of 5-fluorouracil and chitosan was 1:1, the maximum drug loading of nanoparticles was 20.13 ± 0.007%, the encapsulation efficiency was 44.28 ± 1.69%, the particle size was 283.9 ± 5.25 nm and the zeta potential was 45.3 ± 3.23 mV. The prepared nanoparticles had both burst-release and sustained-release phases in vitro release studies. In addition, the inhibitory effect of the prepared nanoparticles on gastric cancer SGC-7901 cells was similar to that of 5-fluorouracil injection, and the blank vector had no obvious inhibitory effect on SGC-7901 cells. In the pharmacokinetic study of rats in vivo , we found that AUC (0−t) , MRT (0−t) and t 1/2z of nanoparticles were significantly increased in vivo compared with 5-fluorouracil solution, indicating that the prepared nanoparticles can play a role in sustained-release.
研究领域:
药剂学
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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
Expert Opinion on Drug Delivery
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2020
·
IF 4.838
Pu Guo,Chao Pi,Shijie Zhao,Shaozhi Fu,Hongru Yang,Xiaoli Zheng,Xiaomei Zhang,Ling Zhao,Yumeng Wei
Background A novel nanoemulsion (CU/FU-LN) was developed as an oral 5-fluorouracil and curcumin co-delivery system for synergistic efficacy against liver cancer.Methods MTT assay, confocal laser scanning microscope, and H&E staining were utilized to establish the efficacy and safety of CU/FU-LN.Results The AUC(0-t) of CU/FU-LN was 8.85-fold and 8.59-fold greater than those of CU and FU, respectively. The IC50 of CU/FU-LN was 4.6-fold and 4.9-fold lower than those of FU and CU in HepG2 cells, respectively. In vivo anti-tumor trials, the tumor inhibition rate was significantly elevated by CU/FU-LN (49.29%), compared 24.84% and 4.72% for FU and CU, respectively. Ki-67 immunohistochemical analysis revealed that CU/FU-LN had an obvious anti-proliferation effect. The IC50 of CU/FU-LN in L02 cells was 1.51-fold and 2.60-fold higher than those of CU and FU, respectively. Certain vital organs in the mice of the CU/FU-LN group showed markedly fewer lesions than those of the CU, FU, and CU+FU groups. The CU/FU-LN treatment caused no significant change in mouse body weight relative to the control group (P > 0.05). Conclusions We successfully prepared a promising co-delivery platform for the synergistic treatment of liver cancer and it has a comparatively enhanced efficacy and mitigated toxicity.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
CRYSTENGCOMM
·
2019
·Vol. 21
·期 34
·5095-5105
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IF 3.382
Xia-Lin Dai,Alexander P. Voronin,Wei Gao,German L. Perlovich,Tong-Bu Lu,Jia-Mei Chen
5-Fluorouracil (5FU) is a BCS class III drug with good aqueous solubility and poor permeability, which severely limits its transdermal permeation through the stratum corneum. Herein, four cocrystals of 5FU with a series of isomeric hydroxybenzoic acids, including salicylic acid (2 : 1), 3-hydroxybenzoic acid (1 : 1) and 4-hydroxybenzoic acid (forms I and II, 1 : 1) were prepared and subjected to membrane permeation. They exhibited significantly improved membrane permeability due to the lipid solubility enhancement caused by cocrystallization. Solid-state DFT computations followed by Bader analysis based on single crystal structures were carried out to quantify the pattern of non-covalent interactions in the cocrystals. The lattice energy values were estimated as a sum of energies of non-covalent intermolecular interactions, which show a negative correlation with the lipid solubility of 1 : 1 cocrystals. This study has important implications for the use of the cocrystallization approach to improve the permeability of transdermal drugs.
研究领域:
药学
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理论化学
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药物递送
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产品关联
DOI
高影响因子
Biomedical Materials
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2021
·Vol. 16
·期 6
·065014
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IF 3.715
Caini Yuan,Xinyun Long,Jinghua Li,Qing Cai
As a biocompatible and biodegradable polymer, poly(lactide-co-glycolide) (PLGA) has been widely used as a carrier to achieve controlled drug delivery in various forms. Focusing on skin tumor treatment, herein 5-fluorouracil (5-FU) was embedded into the core of coaxially electrospun PLGA fibers to get a drug-loaded core–shell fibrous membrane. In the coaxial electrospinning, poly(vinylpyrrolidone) was applied in the inner flow to facilitate the formation of the core–shell structured fibers. The morphology and micro-structure of the fibers were characterized by scanning electron microscope and transmission electron microscope. The influences of the molecular weights and chemical compositions of PLGA copolymers on the release behaviors were studied. The cytotoxicity of the fibers was characterized by cell proliferation and living-dead cell staining experiments. The results showed that faster release rates would be obtained if the copolymers were of lower molecular weights and higher fraction of glycidyl unit. All the prepared 5-FU loaded fibrous membranes were non-cytotoxic, suggesting their potential applications in skin tumor treatment.
研究领域:
药学
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生物医学工程
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOID AND POLYMER SCIENCE
·
2025
·
IF 2.3
Wang Ying,Yang YunXia,Zhu Daliang,Zhang Hongmei,Wang Yanqing
Polysaccharide-based drug delivery systems have gained significant attention due to their biocompatibility and potential for targeted therapy. In this study, we utilized Ganoderma lucidum polysaccharides (GLP) as a macromolecular carrier to synthesize polysaccharide drug conjugates by forming ester bonds with 5-fluorouracil (5-FU) derivatives (5-FUAC). This not only improves the solubility and stability of 5-FU but also enhances its targeted delivery to tumor tissues, potentially reducing systemic toxicity. Utilizing Ganoderma lucidum polysaccharides (GLP) as a macromolecular carrier, we successfully synthesized GLP-5-FU conjugates by forming ester bonds with 5-fluorouracil derivatives (5-FUAC). These conjugates were then characterized using spectrum analysis technologies. The drug loading capacities of 5-FU in the GLP-5-FU conjugates were found to be approximately 4.7%. Morphological observations revealed that the GLP-5-FU conjugates had a regular spherical shape. In terms of drug release, 5-FU was found to be released faster at pH 6.8 compared to pH 7.4. To investigate the dynamic viscoelastic behavior of GLP and GLP-5-FU conjugates in water, dynamic rheology analysis was conducted. In terms of cytotoxicity, the GLP-5-FU conjugates exhibited greater inhibition of proliferation compared to 5-FU and GLP alone in HeLa, 786-O, and SKOV3 cells. Furthermore, the GLP-5-FU conjugates showed lower cytotoxicity to 293A cells. Graphical
研究领域:
药理学
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生物材料
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肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
CRYSTENGCOMM
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2020
·Vol. 22
·期 45
·7992-8006
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IF 3.117
Yue-Ming Yu,Ling-Yang Wang,Fan-Zhi Bu,Lin-Lin Wang,Yan-Tuan Li,Cheng Wang,Zhi-Yong Wu
In order to give full play to the superiority of cocrystallization techniques to overcome biopharmaceutical limitations in vitro and ameliorate pharmacokinetic properties in vivo together with heightening the antitumor abilities of the anticancer drug 5-fluorouracil (FL), and to gain some further insights into the development of novel pharmaceutical cocrystals with synergetic antitumor activity between an active pharmaceutical ingredient and the former cocrystal, a new cocrystal of FL with caffeic acid (CF), namely FL-CF-2H2O, has been successfully exploited and systematically studied. Single-crystal X-ray diffraction analysis confirms that the asymmetric unit of the newly synthesized cocrystal consists of one FL, one CF and two solvent water molecules, in which the two complementary FL and CF molecules compose a planar hydrogen-bonding pair. Water molecules fill in the hole surrounded by three arrays of the pairs and link each other via hydrogen bonds to form a three-dimensional supramolecular network, which is further reinforced by aromatic packing interactions. The cocrystal characteristics in vitro and in vivo are systematically evaluated through a combination of theoretical and experimental methods. It is found that the permeability and solubility of FL from the FL-CF-2H2O cocrystal are synchronously enhanced relative to pure FL, which is supported by molecular electrostatic potential calculation and Hirshfeld surface analysis. Interestingly, the ameliorated in vitro biopharmaceutical characteristics can efficaciously change the in vivo optimized pharmacokinetics with prolonged half-life and increased bioavailability compared with FL itself. What is even more interesting is that CF and FL in the cocrystal exhibit synergistic antitumor effects on tested cell lines. Thus, this work not only provides a new crystalline form for FL with potential application prospects, but also initiates an intelligent idea for the development of synergistic antitumor pharmaceutical cocrystals.
研究领域:
药理学
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肿瘤学
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药物化学
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产品关联
DOI
高影响因子
ANALYST
·
2021
·Vol. 146
·期 8
·2506-2519
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IF 4.616
Yue-Ming Yu,Yuan-Yuan Niu,Ling-Yang Wang,Yan-Tuan Li,Zhi-Yong Wu,Cui-Wei Yan
For highlighting the predominance of phenolic acid nutraceutical ferulic acid (FR) in regulating the in vivo/vitro performances of anticancer drug 5-fluorouracil (Flu) and strengthening their cooperativity in antitumor effect, thus achieving a major breakthrough in the development of drug-nutraceutical cocrystal with synergistic antitumor action, a cocrystallization strategy of dual optimization is created, in which both the in vivo and vitro natures of Flu are improved by exploiting the FR's excellent physicochemical property. Moreover, Flu's anticancer effects were promoted by exerting the assistant antitumor peculiarity of FR. Such dual optimization of FR for Flu in physicochemical properties and anticancer activities is beneficial for realizing synergistic augmentation effect by taking the benefit of the cooperativeness of Flu and FR in the anticancer ability. Based on this idea, a novel cocrystal of Flu and FR, namely, Flu-FR-H2O, is successfully assembled as the first 5-fluorouracil-nutraceutical cocrystal with synergistic antitumor effect and its explicit structure is resolved. The single-crystal X-ray diffraction demonstrates that Flu and FR have a ratio of 1 : 1 with one equivalent of solvent water in the cocrystal, where one-dimensional hydrogen-bonding helices and FR-Flu hydrogen-bonding pairs, together construct a three-dimensional supramolecular network. By combining experimental evaluation with theoretical analysis, in vitro/vivo pharmaceutical properties are scientifically investigated. Results show that the permeability and aqueous solubility of Flu are respectively elevated by 5.08 and 1.64 folds, which has brought about ameliorated pharmacokinetics, thus providing prolonged retention time and increased oral bioavailability. More interestingly, the cocrystal shows synergistic inhibition ability of Flu and FR against tested tumor cell strains, hence laying the groundwork for reducing the dosage and even the toxic side effects of Flu. As a result of this, the present research not only provides a new strategy for Flu to optimize its physicochemical properties and antitumor activities simultaneously but also offers some opinions for the development of synergistic antitumor pharmaceutical cocrystals.
研究领域:
药学
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肿瘤学
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材料科学
✓ 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）