DRUG DELIVERY
·
2015
·
IF 2.558
Yuee Cai,Zhongqing Sun,Xiaobin Fang,Xiefan Fang,Fei Xiao,Yitao Wang,Meiwan Chen
Curcumin (CUR), a nontoxic polyphenol derived from the rhizome of turmeric (Curcuma longa), has been recognized as an anti-cancer and chemo-preventative agent. However, its clinical application for cancer treatment has been greatly limited due to its poor water-solubility and low bioavailability. To tackle this problem, Pluronic F68–CUR (F68–CUR) conjugate micelles, which are amphiphilic copolymers, were designed and synthesized in this study. These highly stable micelles with CUR concentrated in the core were formulated using the solvent evaporation method and were confirmed by Fourier transform infrared spectroscopy and nuclear magnetic resonance. Physicochemical characterization of F68–CUR conjugate micelles revealed that high drug loading content (DL%; 0.248 mg CUR/1 mg F68) was achieved, and the average particle size of micelles was 115.2 ± 3.0 nm. Compared with free CUR, a significantly higher cytotoxicity against human breast cancer cell line MDA-MB-231 was observed in F68–CUR conjugate micelles. The IC50 value of F68–CUR conjugate micelles was 1.95-fold lower than that of free CUR, indicating that the anti-cancer activity of CUR was significantly improved in the micelles. Furthermore, apoptotic studies demonstrated that F68–CUR conjugate micelles induced more cell apoptosis than that of free CUR. Taken together, these results demonstrate that F68–CUR conjugate micelles are promising to improve the clinical effectiveness of CUR in cancer treatment.
研究领域:
药学
·
肿瘤学
·
生物化学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
·
2025
·
IF 3.9
Jiaying Li,Tingyuan Li,Mingjie Gong,Xiaowen Wang,Qinyang Hua,Xia Jiang,Qilong Wang,Elmurat Toreniyazov,Jiangnan Yu,Xia Cao,Michael Adu-Frimpong,Ximing Xu
Phloretin exhibits strong antioxidant and anti-ageing properties by inhibiting mitochondrial oxidation of glutamate, succinic acid, and ascorbic acid. However, its clinical application is limited by poor aqueous solubility and low oral bioavailability. To enhance its bioavailability and efficacy, we incorporated phloretin into nano-micelles (phloretin-MM) using the thin film dispersion method. Characterisation revealed that the optimal formulation had TPGS and Pluronic F68 in a 4:1 ratio as the excipients, which resulted in spherical micelles with an average particle size of 33.28 nm and an encapsulation efficiency of 71.2 ± 0.48%. The in vitro release profile showed that the phloretin-MM showed significantly higher cumulative release rates than free phloretin across various pH conditions, while the pharmaceutical analysis in rats indicated that phloretin-MM significantly improved the oral bioavailability of phloretin (about 5 folds) in circulation. Additionally, through the analysis of the staining of zebrafish under light microscopy and the average gray value, it can be concluded that phloretin has anti-ageing drug effect, and phloretin-MM is better than free phloretin. These findings suggest that TPGS/Pluronic F68-modified phloretin-MM could serve as an excellent nano-drug carrier system, potentially enhancing the solubility, bioavailability, and anti-ageing effects of phloretin for broader clinical applications.
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产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2016
·Vol. 18
·期 1
·147-155
·
IF 1.954
Fang Xiaobin,Xu Yingqi,Wang Shengpeng,Wan Jianbo,He Chengwei,Chen Meiwan
Gambogic acid (GA), a natural compound from gamboge resin, has been introduced as a promising antitumor drug contributing to its broad spectrum of antitumor activity. However, the poor aqueous solubility and short half-life hinder its clinical application. Pluronic F68 (F68) is a well-known amphiphilic block copolymer consisting of hydrophobic propylene oxide units and hydrophilic ethylene oxide. Although F68 has an amphiphilic structure, its short propylene oxide segment limits its dilution stability and drug-loading capacity. To overcome this limitation, we modified F68 by conjugating linoleic acid, a hydrophobic fatty acid, to increase the hydrophilic-hydrophobic interaction and thus improve the stability of F68 nano-spheres. This F68-linoleic acid (F68-LA) conjugate was synthesized and was used to load GA to improve its anticancer effects. GA-loaded F68-LA nano-spheres were stable for 6 days, with a mean diameter of 159.3 nm and zeta potential of −23.2 mV. The entrapment efficiency of GA in F68-LA nano-spheres was as high as 92.0%. Furthermore, F68-LA/GA nano-spheres exhibited an enhanced cytotoxic activity and proapoptotic effect against human ovarian cancer A2780 cells, compared with free GA. Our results showed that the F68-LA/GA nano-spheres might be a promising cancer-targeted drug delivery system in ovarian cancer therapy.
研究领域:
药学
·
纳米技术
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2016
·
IF 3.994
Xiao-Bin Fang,Jin-Ming Zhang,Xi Xie,Di Liu,Cheng-Wei He,Jian-Bo Wan,Mei-Wan Chen
Curcumin (Cur) is a highly pleiotropic anticancer agent that inhibits cell proliferation and induces apoptosis in cancer cells. A variety of nano-systems constituted by polymer–drug conjugates have been designed to overcome its shortages on water solubility, chemical instability, and poor bioavailability. However, most of them suffer from ineffective release of Cur in cancer cells in vivo . This work developed a novel flexible acid-responsive micelle formulation by covalently conjugating Cur on the hydrophilic terminals of pluronic F68 chains via cis -aconitic anhydride linkers. The synthesized F68-Cis–Cur conjugates can readily precipitate to form homogeneous micelles with average size about 100 nm in aqueous solution. In acid environments, F68-Cis–Cur conjugates would break down and subsequently release Cur rapidly, for the reason of pH-sensitive cleavage of cis -aconitic anhydride linkers. In vitro anticancer activity tests demonstrated that F68-Cis–Cur micelles induced higher cytotoxicity against both A2780 and SMMC 7721 cells than free Cur. It provided a larger decrease of mitochondrion membrane potential and induced cellular apoptosis. F68-Cis–Cur micelles remarkably increased cellular uptake of Cur than free Cur through caveolae-mediated endocytosis in an energy-dependent manner. This study demonstrates F68-Cis–Cur conjugation as a promising tool for improving intracellular drug delivery in cancer therapy.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2024
·Vol. 25
·期 6
·1-15
·
IF 3.4
Chen Jiasheng,Chen Zhenzhen,Wang Wentao,Wang Liyang,Zheng Jiaqi,Wu Shiqiong,Pan Yuru,Li Sai,Zhao Jie,Cai Zheng
Some glycoside drugs can be transported through intestinal glucose transporters (IGTs). The surfactants used in oral drug preparations can affect the function of transporter proteins. This study aimed to investigate the effect of commonly used surfactants, Poloxamer 188 and Tween 80, on the drug transport capacity of IGTs. Previous studies have shown that gastrodin is the optimal drug substrate for IGTs. Gastrodin was used as a probe drug to evaluate the effect of these two surfactants on intestinal absorption in SD rats through pharmacokinetic and in situ single-pass intestinal perfusion. Then, the effects of the two surfactants on the expression of glucose transporters and tight-junction proteins were examined using RT-PCR and western blotting. Additionally, the effect of surfactants on intestinal permeability was evaluated through hematoxylin-eosin staining. The results found that all experimental for Poloxamer 188 (0.5%, 2.0% and 8.0%) and Tween 80 (0.1% and 2.0%) were not significantly different from those of the blank group. However, the AUC (0-∞) of gastrodin increased by approximately 32% when 0.5% Tween 80 was used. The changes in IGT expression correlated with the intestinal absorption of gastrodin. A significant increase in the expression of IGTs was observed at 0.5% Tween 80. In conclusion, Poloxamer 188 had minimal effect on the drug transport capacity of IGTs within the recommended limits of use. However, the expression of IGTs increased in response to 0.5% Tween 80, which significantly enhanced the drug transport capacity of IGTs. However, 0.1% and 2.0% Tween 80 had no significant effect. Graphical Abstract
研究领域:
药剂学
·
药理学
·
肠道吸收
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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）