RSC Advances
·
2015
·Vol. 5
·期 49
·38810-38817
·
IF 3.84
Yeping Li,Jingbo Xu,Yun Xu,Liying Huang,Junli Wang,Xiaonong Cheng
The objective of the study is to describe a new approach of combining quantum dots into chitosan as an anti-cancer drug carrier. Novel chitosan–ZnSe/ZnS (CS–ZnSe/ZnS) nanoparticles were synthesized by a one-step ionic gelation technique, with ZnSe/ZnS quantum dots (ZnSe/ZnS QDs) as cross-linking agent and for fluorescent labeling. The approach not only avoids the use of emulsifiers and chemical cross-linking agents but also prevents the possibility of damage to drugs. The fluorescent CS–ZnSe/ZnS nanoparticles were about 100–500 nm in size and stable in a physiological environment. Low cytotoxicity was ensured by investigation with mouse lung carcinoma cells. The cell viability remained 99% when the concentration of CS–ZnSe/ZnS nanoparticles increased to 200 μg mL−1. In the in vitro drug release experiment, 5-fluorouracil (5-Fu) loaded within CS–ZnSe/ZnS nanoparticles had more preferable sustained-release performance and longer equilibrium time compared with that of the pure 5-Fu. The fluorescent CS–ZnSe/ZnS nanoparticles are expected to be used for biological fluorescent labeling and drug carriers.
研究领域:
生物材料学
·
纳米医学
·
药剂学
✓ 已验证
DOI
高影响因子
CRYSTENGCOMM
·
2020
·Vol. 22
·期 21
·3670-3682
·
IF 3.117
Xia-Lin Dai,Chao Wu,Jin-Hui Li,Lian-Chao Liu,Xin He,Tong-Bu Lu,Jia-Mei Chen
5-Fluorouracil (5FU) is a classical anti-metabolic drug with broad-spectrum antitumor effects. However, the oral absorption of 5FU is incomplete with a short biological half-life and an obvious peak-valley phenomenon, leading to the frequent administration requirement and severe side effects. Herein, a pharmaceutical cocrystallization approach based on crystal engineering was employed to modulate the pharmacokinetic properties of 5FU by changing its aqueous solubility. Four cocrystals of 5FU with a group of dihydroxybenzoic acids were synthesized and characterized. The powder dissolution experiments showed that all the cocrystals exhibited different aqueous solubilities and dissolution rates in comparison with pure 5FU. As compared to pure 5FU, the apparent solubility values of two cocrystals were increased by 34% and 11% while those of the other two cocrystals were reduced by 27% and 51%, respectively. The pharmacokinetic parameters of all the cocrystals, including Cmax, tmax, MRT0–t, t1/2 and AUC0–t, as well as the shape of the pharmacokinetic curves, were accordingly altered in the in vivo pharmacokinetic study. This study has important implications for using cocrystallization techniques to modulate the pharmacokinetic properties of drugs with undesirable oral absorption, especially to avoid the in vivo peak-valley effect and reduce side effects in clinical practice.
研究领域:
药物化学
·
药理学
·
晶体工程
✓ 已验证
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Ahmed M. Omer,Eman M. Abd El-Monaem,Heba S. Hassan,Mahmoud A. Elmeligy,Angela Kleinová,Abdelazeem S. Eltaweil,Abolfazl Heydari
pH-sensitive carriers have emerged as an optimal choice for the oral administration of anticancer drugs, exhibiting the desired release performance. This study aims to develop biocomposite beads for the sustained release of the anticancer drug 5-fluorouracil (5-FU). Here, 5-FU was encapsulated within a ZIF-8 metal-organic framework (MOF), which was subsequently impregnated into amino-chitosan beads. The resulting Am-CS@ZIF-8 biocomposite beads were characterized for their chemical structure, surface morphology, elemental composition, crystallinity, surface charges, and mechanical properties utilizing Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), zeta potential analysis, and a texture analyzer, respectively. The developed beads exhibited a textured surface, denser composition, and a positively charged surface with a maximum zeta potential of +12.4 at pH 7.4. In comparison to Am-CS beads, the Am-CS@ZIF-8 biocomposite beads demonstrated superior mechanical properties, achieving a maximum stress value of 5.668 MPa compared to the 1.874 MPa recorded for pure Am-CS beads. pH sensitivity was assessed through the investigation of water uptake behavior at pH 1.2 and pH 7.4. The Am-CS@ZIF-8 biocomposite beads demonstrated a high encapsulation efficiency of approximately 81.6 % for 5-FU. They exhibited pH-responsive release behavior, with only 17 % of the drug released at pH 1.2 after 2 h and a sustained release of 52 % at pH 7.4 over 24 h. The release mechanism was predominantly governed by Fickian diffusion, as closely fitted by the Peppas-Sahlin kinetic model. The formulated carrier confirmed its biodegradability under enzymatic physiological conditions, suggesting its potential applicability as an effective system for the oral delivery of anticancer drugs.
研究领域:
药剂学
·
生物材料学
✓ 已验证
产品关联
DOI
高影响因子
POWDER TECHNOLOGY
·
2024
·
IF 4.5
Han Hao,Tiantian Ren,Cuilu Quan,Jing Wang
Arginine (ARG) is a precursor for producing NO, which can relax vascular smooth muscle. We herein report cocrystals screened by powder grinding using chiral ARG to improve the bioavailability of 5-fluorouracil (5-FU) and alleviate 5-FU induced cardiotoxicity. The results of powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) inferred the formation of new solid phases. Hydrogen bonding interactions between C=O group and N-H were supported by Fourier transform infrared (FTIR) spectroscopy. The spectra intensity of circular dichroism (CD) of cocrystals were higher than that of ARG after combined with non-optically active 5-FU. The bioavailability and cytotoxicity of 5-FU were enhanced by cocrystallization. Notably, L-cocrystal prepared using biologically active L-ARG released lower dose NO in human umbilical vein endothelial cells (HUVEC) cells than that of D-cocrystal. D-cocrystal performed higher NO release ability by non-enzymatic pathway, indicating a greater potential to alleviate cardiotoxicity. 5-FU-induced cardiotoxicity in rats was effectively alleviated, proved by the least increased LDH, cTnI and CK-MB level induced by D-cocrystal.
研究领域:
药学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
Beibei Hu,Yue Yuan,Yun Yan,Xiaoping Zhou,Yue Li,Qiming Kan,Sanming Li
A novel bolaamphiphile surfactant N , N ′-(dodecane-1, 12-diyl) bis (2,6-diaminohexanamide) (DADL) was designed and synthesized using l -lysine and 1,12-diaminododecane as the hydrophilic and hydrophobic part, respectively. After separation and purification, the structure of the synthetic bolaamphiphile surfactant was verified by FTIR, MS and 1 H NMR. The synthetic bolaamphiphile was able to self-assemble to form vesicles. After formulation screening, vesicles loaded with 5-Fluorouracil (5-Fu) were prepared with Tween 60 and DADL by sonication and were examined by dynamic light scattering and transmission electron microscopy. Micro-FTIR was applied to investigate the conformation of the bola molecules within the vesicle membrane. The release profile of the vesicles showed a pH-sensitive and sustained release. No significant toxicity was observed in an in vitro cell viability assay. The antitumor efficacy of the 5-Fu-loaded vesicles on H 22 tumor-bearing mice was remarkably high due to the EPR effects. These results show that our novel bolaamphiphile derived from lysine has excellent potential as a pH-sensitive drug carrier.
研究领域:
药剂学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Onyinyechi Lydia Ugorji,Ikechukwu Virgilius Onyishi,Amarauche Chukwu,Anthony Amaechi Attama
5-flourouracil (5-FU) is typically modulated with leucovorin (LEU) in clinical practice to improve clinical efficacy and patient survival rates. However, this combination has undesirable side effects and makes 5-FU more toxic. Hence, integrating a vesicular system (proniosomes) with another delivery vehicle may improve drug targeting, while resolving the aforementioned drawbacks. This study aimed to engineer 5-FU/LEU proniosomes for possible delivery to the colon. The modified slurry approach was used to create drug-loaded proniosomes (150 mg/9 g of carrier) using both water-soluble (dextrin (DEX) and lactose (LAC)) and insoluble (Neusilin FH 2 (NEU)) carriers. The powdered formulations were filled into Eudragit S100 (10 %)-coated capsules or Eudragit FS 30D capsules for enteric- or colon-specific delivery. In vitro evaluations (flow properties, powder X-ray diffractometry (XRD) analysis, particle size analysis, entrapment efficiency, drug release, scanning electron microscopy (SEM), polydispersity index, Fourier transform infrared spectroscopy (FTIR), and stability studies) were performed on the formulations. An in vitro cytotoxicity test [real-time cell assay (RTCA)] against HCT-116 colon cancer cell lines was performed using the optimized formulation. In vitro evaluations showed that the nanoparticles had good physicochemical properties. RTCA studies showed sustained cell death with the formulations compared to the pure drug and placebo. The sequential drug release of the colon-targeted capsules containing 5-FU and LEU- loaded proniosomes showed negligible drug release in SGF (pH 1.2) and phosphate buffer solution (pH 6.8) (approximately 11 %) but profound drug release (>80 %) at pH 7.4. Drug-loaded proniosomes engineered for colon targeting (Eudragit S100 (10 %) capsules or Eudragit FS 30D capsules) showed good colon-specific targeting and favorable in vitro cytotoxicity profiles.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2024
·Vol. 14
·期 34
·24942-24951
·
IF 3.9
Zhongyi Guo,Kang Fu,Jingyi Sun,Wenhao Du,Qisheng Hao,Xiao Hu
Nanodrug delivery systems (NDDS) have been proposed to improve the targeting and bioavailability of chemotherapy drugs. The approach of drug loading via physical adsorption is facile to operate; however, there exists a risk of premature leakage. Coupling the drug molecules with the carrier through chemical reactions can guarantee the stability of the drug delivery process, yet the preparation procedure is relatively intricate. In this research, a kind of Prussian blue nanocage (PB Cage) was fabricated, and the phase change material, 1-pentadecanol, was used as the gating material to solidify 5-fluorouracil (5-FU) inside the nanocage. Upon irradiation with near-infrared (NIR) light, the temperature of the PB Cage can rise rapidly. When the temperature exceeds 43 °C, 1-pentadecanol undergoes a solid–liquid phase transition and subsequently releases 5-FU to inhibit DNA synthesis. Meanwhile, the photothermal therapy (PTT) mediated by the PB Cage is also capable of ablating tumor cells. The NDDS constructed based on PB has achieved the precise release of 5-FU triggered by NIR light, which may avoid side effects on normal tissues. Moreover, the combination of chemotherapy and photothermal therapy can efficaciously suppress the proliferation of tumor cells.
研究领域:
药物递送系统
·
肿瘤治疗
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Junzhe Fu,Weijiang Yu,Yixian Mu,Xuedan Qian,Xinyi Li,Ke Sun,Youxiang Wang,Jian Ji
Hypertrophic scars (HS) result from aberrant wound healing, often leading to disfigurement and functional impairment. Hypoxia is a prominent feature of HS; however, its impact on therapeutic efficacy remains unexplored, presenting a potential pathway for advancing HS treatments. Here, hypoxia is identified as a limiting factor in the efficacy of 5-fluorouracil (5-Fu), a widely used clinical drug for HS. At the gene expression level, 5-Fu response genes associated with the mitotic cell cycle, such as BUB1 and SPAG5, fail to be downregulated under hypoxia in human HS fibroblasts, contributing to the altered cytotoxic response. To address this limitation, an oxygen-popping microneedle (MN) system is developed to alleviate hypoxia in HS and enhance 5-Fu-based therapy. Inspired by the gas-release mechanism of Pop Rocks candy, high-pressure oxygen-trapping particles (HOTP) are formulated and integrated into a core–shell MN platform, enabling localized co-delivery of oxygen and 5-Fu. The popping release of oxygen also facilitates 5-Fu penetration into dense HS tissue. In vivo studies provide strong evidence that the MN system effectively mitigates hypoxia, significantly enhancing the therapeutic efficacy of 5-Fu. This research presents an innovative strategy for optimizing HS therapy by alleviating hypoxia, with the potential to inform future advancements in HS treatment.
研究领域:
医学
·
生物材料学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
Analytical Methods
·
2019
·Vol. 11
·期 39
·4977-4982
·
IF 2.378
Xiaolin Jiang,Ke Ma,Cuihua Hu,Mingyan Gao,Jiashuo Zhang,Ying Wang,Yujuan Chen,Zhengxun Song,Zuobin Wang
Atomic force microscopy (AFM) can be used to obtain the physical information of single live cancer cells; however, the physical changes in live cells with time based on AFM remain to be studied, which play a key role in the evaluation of the efficacy and side effects of drugs. Herein, the treatment of the A549 cell line with the anticarcinogen 5-fluorouracil has been discussed based on the AFM analysis of their continuous physical changes, including their surface morphology, height, adhesion and Young's modulus, with time. In comparison, the African green monkey kidney (Vero) cell line was tested as normal cells to determine the side effects of 5-fluorouracil. The results show that the optimal concentration of 5-fluorouracil is about 500 μM, which presents the best anticancer effect and mild side effects.
研究领域:
生物医学工程
·
肿瘤学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Xubao Jiang,Suisui Wang,Xiang Zheng Kong
Pyrimidines, in particular uracil (UL) and 5-fluorouracil (5FU), are well known anticancerogens and widely used against a variety of cancers. An important concerning issue has been their monitoring and detection in order to adequately control their doses and to minimize their health hazards. Among a variety of methods developed, fluorescence sensing is gaining more attention because of its accuracy, easy operation, and straight visuability. However, in most of the reported studies, the sensors are made from transition metals with sophisticated multi-processes; polymers, particularly biopolymers, are hardly available. We demonstrate herein that aqueous solution of poly(ethylene glycol) (PEG), a commonly known biopolymer, is highly emissive under excitation of 280 nm. While the solutions of selected pyrimidines, i.e. UL and 5FU, are non-emissive under the same excitation, their addition to PEG solution, however, brings about a distinct and concentration dependent quenching for PEG emission. PEG was then used as sensor with good stability for UL and 5FU detections in water. The tests were also done by spiking 5FU in tap water, milk and synthetic urine, confirming that 5FU was practically fully recovered in all the cases. The quenching was ascribed to the interaction between PEG clusters and the heteroatoms on pyrimidine molecules through hydrogen bonding, which is supported by multi-technical analyses, including NMR, FTIR and cluster size tests by DLS. This work provides therefore a full green, easy to operate, low-costing, novel and reliable protocol for pyrimidine monitoring and detection, with the quenching mechanism interpreted based on multi-technical characterizations.
研究领域:
生物化学
·
医学检测
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Inorganics
·
2022
·Vol. 10
·期 11
·202
·
IF 3.149
Liang Qin,Fenglan Liang,Yan Li,Jiana Wu,Shiyuan Guan,Meiyin Wu,Shiling Xie,Manshi Luo,Deyun Ma
A hydrostable 2D Zn-based MOF, {[Zn(5-PIA)(imbm)]·2H2O}n(1) (5-H2PIA = 5-propoxy-isophthalic acid, imbm = 1,4-di(1H-imidazol-1-yl)benzene), was synthesized and structurally characterized. Complex1shows good water and thermal stability based on the TGA and PXRD analyses and displays a 2D framework with 1D channels of 4.8 × 13.8 and 10.0 × 8.3 Å2along theaaxis. The 5-fluorouracil (5-FU) payload in activated complex1(complex1a) is 19.3 wt%, and the cumulative release value of 5-FU at 120 h was about 70.04% in PBS (pH 7.4) at 310 K. In vitro MTT assays did not reveal any cytotoxic effect of NIH-3T3 and HEK-293 cells when the concentration of1was below 500 μg/mL and 5 μg/mL, respectively. No morphological abnormalities were observed on zebrafish exposed to complex1.Keywords:zinc-organic framework;drug delivery;5-fluorouracil;MTT assays;zebrafish toxicity
研究领域:
材料科学与工程
·
医学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
Pharmaceuticals
·
2022
·Vol. 15
·期 7
·881
·
IF 5.215
Tianyu Chen,Hui Chen,Yichun Jiang,Qi Yan,Shuling Zheng,Min Wu
In this research, KLA-modified liposomes co-loaded with 5-fluorouracil and paclitaxel (KLA-5-FU/PTX Lps) were developed, and their antitumor activity against triple-negative breast cancer (TNBC) was evaluated. KLA-5-FU/PTX Lps were prepared using the thin-film dispersion method, and their in vitro anticancer efficacy was assessed in human breast cancer cells (MDA-MB-231). An MDA-MB-231 tumor-bearing mouse model was also established to evaluate their antitumor efficacy in vivo. KLA-5-FU/PTX Lps showed enhanced cytotoxicity against MDA-MB-231 cells, improved drug delivery to mitochondria, and induced mitochondria-mediated apoptosis. The modified liposomes also showed favorable antitumor activity in vivo due to their strong ability to target tumors and mitochondria. The liposomes showed no obvious systemic toxicity. Our results suggest that KLA-5-FU/PTX Lps are a promising system with which to target the delivery of antitumor drugs to mitochondria as a treatment for TNBC.Keywords:5-fluorouracil;paclitaxel;liposomes;mitochondrial targeting;TNBC
研究领域:
药理学
·
肿瘤学
·
纳米技术
✓ 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）