JOURNAL OF PHARMACEUTICAL SCIENCES
·
2024
·
IF 3.7
Yuanfeng Wei,Xin Chen,Runxue Ding,Jingwen Zhang,Hui Chen,Junxiao Zhu,Jianjun Zhang,Peiya Shen
Different from salt, metal chelate is a novel state of drug constructed by more separate coordinate bonds to form a chelating circle. Due to their composition similarity, it is hard to distinguish them except identifying ionic bond (i.e., salt) or coordinate bond (i.e., chelate) in the single crystal structure. In this study, sodium chelate (CDCC No: 1865670) and lithium salt (CDCC No: 2161617) of puerarin (PUE) was prepared. In addition to difference in single crystal structure, it was found that they showed totally different phase solubility behaviors: lithium salt demonstrated a typical inverse proportion curve as other common salts, while sodium chelate exhibited disordered scatters. However, when incorporating the unit PUE-Na complex in solution state and complexation constant K 11 in chemical equation, the scatters in phase solubility diagram of chelate could be well fitted and the value of K 11 was dramatically higher with orders of magnitude than the dissociation constant K c ; while processing phase solubility curve of lithium salt by incorporating complex item, it could not well match the curve at all. PUE sodium chelate is more likely to be a weak electrolyte with partial dissociation, while PUE lithium salt acted as a strong electrolyte with complete dissociation. The phase solubility test would be served as a surrogate tool for differentiation of chelates from salts when single crystal was not available.
研究领域:
药学
·
化学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Tongkai Chen,Wei Liu,Sha Xiong,Dongli Li,Shuhuan Fang,Zhenfeng Wu,Qi Wang,Xiaojia Chen
Recent work has highlighted the potential of puerarin (PU) as a valuable compound to treat Parkinson’s disease (PD), but its undesirable water solubility and bioavailability have constrained its utility. In this study, we sought to develop nanoparticles (NPs) that could be used to encapsulate PU, thereby extending its in vivo half-life and improving its bioavailability and accumulation in the brain to treat the symptoms of PD. We prepared spherical NPs (88.36 ± 1.67 nm) from six-armed star-shaped poly(lactide-co-glycolide) (6-s-PLGA) NPs that were used to encapsulate PU (PU-NPs) with 89.52 ± 1.74% encapsulation efficiency, 42.97 ± 1.58% drug loading, and a 48 h sustained drug release. NP formation and drug loading were largely mediated by hydrophobic interactions, while changes in the external environment led these NPs to become increasingly hydrophilic, thereby leading to drug release. Relative to PU alone, PU-NPs exhibited significantly improved cellular internalization, permeation, and neuroprotective effects. Upon the basis of Förster resonance energy transfer (FRET) of NPs-administered zebrafish, we were able to determine that these NPs were rapidly absorbed into circulation whereupon they were able to access the brain. We further conducted oral PU-NPs administration to rats, revealing significant improvements in PU accumulation within the plasma and brain relative to rats administered free PU. In MPTP-mediated neurotoxicity in mice, we found that PU-NPs treatment improved disease-associated behavioral deficits and depletion of dopamine and its metabolites. These findings indicated that PU-NPs represent a potentially viable approach to enhancing PU oral absorption, thus improving its delivery to the brain wherein it can aid in the treatment of PD.
研究领域:
药剂学
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神经科学
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生物医学工程
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DOI
PubMed
高影响因子
Current Drug Delivery
·
2021
·Vol. 18
·期 10
·1585-1594
·
IF 2.565
Chen Jianmin,Wang Meixia,Ran Mengnan,Liu Xinying,Liu Siwan,Ruan Zhipeng,Jin Nan
Background: The clinical application of glabridin in treating skin diseases has been constrained by the limitations of its poor chemical stability and low skin permeability. Objective: Here, we describe Tip-loading Dissolving Microneedles (TDMNs) encapsulating drugs only in the
tips of needles for glabridin delivery with improved stability and skin permeability. Methods: The TDMNs fabricated by solvent casting technique had sufficient mechanical strength to penetrate through the excised rat's skin without fracture. Drug delivery efficiency and drug residual
in the skin of TDMNs were 63.16% and 49.28%, respectively. Glabridin encapsulated in the tips of TDMNs was effectively delivered into the abdominal skin of rat, and the in vivo delivery efficiency was inversely proportional to the drug doses. Results: Transepidermal Water Loss (TEWL)
significantly increased to 34.80 g/m2·h after the application of TDMNs and returned to normal levels (11.31 g/m2·h) after 8 h, indicating that the TDMNs were well tolerated. The stability of glabridin at room temperature was appreciably improved when loaded in TDMNs. Conclusion:
These results suggest that intradermal delivery of glabridin by TDMNs is a safe and efficient alternative to currently available routes of administration.
研究领域:
药剂学
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皮肤科学
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生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2018
·
IF 3.412
Xiao-Feng Li,Tingting Yuan,Haixia Xu,Xuan Xin,Guanglei Zhao,Hui Wu,Xinglong Xiao
Puerarin, an important isoflavonoid from the edible root of Pueraria lobata, shows multiple bioactivities but suffers from low bioavailability. In this study, a new whole-cell catalytic method for acylation modification of puerarin was developed. Among the 12 strains tested, Aspergillus oryzae showed the highest catalytic activity and selectively catalyzed acylation of puerarin at the 6″-hydroxyl group. The organic solvents used significantly influenced the catalytic efficiency of the cells. In the green solvent 2-methyltetrahydrofuran, the reaction showed high substrate conversion (92.5%) and regioselectivity (95.8%), with results similar to those with tetrahydrofuran (94.2% and 98.5%, respectively) under optimal conditions. The monoester products showed higher liposolubility in comparison to puerarin, and those with C3–C8 fatty acid chain lengths showed evidently improved antioxidant activity toward erythrocyte hemolysis. Considering the operational stability of the cells and efficiency of the scaled-up reactions, this method is efficient and cost effective, with promising applications in the health food industry.
研究领域:
药理学
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生物化学
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食品科学
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2017
·
IF 4.529
Shuya Wang,Ziwei Yang,Na Peng,Jun Zhou,Xiaoyu Yong,Haoran Yuan,Tao Zheng
Ionic liquids-based microwave-assisted hydrolysis was successfully applied for hydrolysis of puerarin and daidzein derivatives from Radix Puerariae Lobatae extract. The ionic liquids with different cations and anions have been investigated, and [Omim]HSO 4 was selected as catalyst. In addition, the hydrolysis parameters, including catalyst quantity, ionic liquids concentration, microwave power and microwave time, were optimized by Response Surface Methodology. The optimal conditions were as follows: 0.82 mol/L [Omim]HSO 4 ; catalyst quantity, 1.42 mL; microwave time, 7 min; microwave power, 400 W. Under those condition the average hydrolysis efficiency of puerarin and daidzein derivatives was 57.93 ± 3.08%. Compared with the traditional acidic catalysts, the [Omim]HSO 4 exhibited higher efficiency, which demonstrates that ionic liquids-based microwave-assisted hydrolysis was a rapid, efficient, and simple hydrolysis technique.
研究领域:
中药化学
·
分析化学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Zhiqiang Guo,Mengdie Tian,Min Zhou,Zhuoer Li,Meijun Li
In this study, the formation of the immunoglobulin G-glabridin (IgG-GB) complex and nanocomplex was analyzed by assessing the structure, stability, solubility, and anticancer effects against the human epithelial ovarian cancer cell line SKOV3. The hydrodynamic sizes of the prepared IgG-GB nanocomplex were 190.1 ± 25.68 nm (PDI: 0.19 ± 0.02), and the solubility levels of GB in the free and nanoformulated forms were 97.28 μg/mL and 368.95 ± 59.63 μg/mL, respectively. Additionally, the IgG-GB nanocomplex exhibited a slower and more sustained release of GB in a pH-sensitive manner. Spectroscopic measurements indicated logKb values of 4.01 and 4.66 for the IgG-GB complex and the IgG-GB nanocomplex, respectively. Furthermore, the main reaction type between IgG and GB was found to be hydrophobic forces, which led to the partial folding of IgG and nanoformulated IgG. Cellular assays demonstrated that the IC50 concentrations of GB, the IgG-GB complex, and the IgG-GB nanocomplex in ovarian cancer SKOV3 cells were 10.74, 10.05, and 6.39 μM, respectively, while these amounts were > 77.84 μM in normal epithelial FHC cells. Moreover, the IgG-GB nanocomplex resulted in increased membrane leakage, mitochondrial dysfunction, and upregulation of Bax/Bcl-2 and caspase-3, along with caspase-3 activity determined by LDH, MP, real-time PCR, and enzyme activity assays. In conclusion, an efficient IgG-GB nanocomplex was potentially prepared and developed as a selective anticancer system against ovarian cancer cells.
研究领域:
药理学
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肿瘤学
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生物化学
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2012
·
IF 2.888
Li Jiang,Jundong Dai,Zhenlin Huang,Qinghua Du,Jiahao Lin,Yurong Wang
Gastrodin (Gas) and puerarin (Pur) are bioactive substances derived from traditional Chinese medicine Gastrodia elata and Radix Puerariae , respectively, which were often used together in Chinese clinical prescriptions. Their injections were used in combined way for treatment of some cardiocerebrovascular diseases in clinic, especially for vertigo due to vertebrobasilar ischemia. In this paper, interaction of gastrodin and puerarin in rat plasma pharmacokinetics via intragastic ( i.g. )/intravenous ( i.v. ) administration was investigated. A reliable HPLC method was developed for simultaneous determination of Gas and Pur in rat plasma with a linear range of 0.101–101 μg/mL for Gas and 0.0500–5.98 μg/mL for Pur ( r 2 > 0.993). The LLOQ, LOD of Gas and Pur were determined to be 0.101, 0.0486 μg/mL, and 0.05, 0.0245 μg/mL, respectively. The intra-day and inter-day precision were all less than 12.0%, whilst the accuracy were all within 96.4 ± 6.00%. The proposed method has been successfully applied to the pharmacokinetic study of the analytes in rats after i.g. / i.v. administration of Gas and Pur alone or combined with each other ( i.g. : 40 mg/kg Gas, 400 mg/kg Pur; i.v. : 20 mg/kg Gas, 20 mg/kg Pur). Blood samples were collected from retinal vein plexus of rats at predetermined time points and plasma containing the internal standard tyrosol (IS) were precipitated by methanol and chromatography was carried out on a C 18 column with a gradient mobile phase of ACN–H 2 O with 0.05% phosphoric acid as a modifier. The pharmacokinetic profiles of combined administration were found to be distinct from those of given alone. The C max , T max , T 1/2 , MRT of Gas administrated alone or combined with Pur via i.g. were 21.7 μg/mL, 0.250 h, 2.81 h, 0.830 h and 18.4 μg/mL, 0.550 h, 0.970 h, 1.37 h, respectively, of Pur administrated alone or combined with Gas via i.g. were 0.490 μg/mL, 1.95 h, 1.33 h, 2.10 h and 2.01 μg/mL, 0.570 h, 4.00 h, 5.10 h, respectively. The relative oral bioavailability of Pur in combined administration was 10.7 times as much as that of single administration, whilst 1.52 folds in Gas. These results indicate that co-administration of Gas and Pur is a promising combination to gain higher bioavailability and it is suggested that doctors pay more attention to the dosages of the two when simultaneously using both of them.
研究领域:
药理学
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中药学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2021
·
IF 3.981
Lan Mo,Guang-lei Zhao,Xiao-feng Li,Xing-long Xiao,Ning He,Hai-xia Xu,Yi-gang Yu
Design and synthesis of prodrugs is an effective strategy to develop new drugs. Puerarin is well-known for its pharmacological properties in the treatment of many cardiovascular and cerebrovascular related diseases. To cope with its poor liposolubility that limited practical applications, we successfully developed a new type of clean and efficient esterification medium for acylation modification of puerarin and studied the relative oral absorption, including pharmacokinetics , tissue distribution and metabolite after oral taking of puerarin acid esters in comparison with free puerarin in rats. In the 1-Ethyl-3-Methylimidazoliumacetate, puerarin had the good solubility, and the reaction showed great initial rate (46.71 mmol/(L*h)) and substrate conversion (63.91%). The results of oral absorption showed that the administration of long-chain fatty acid esters of puerarin, puerarin hexanoate and puerarin myristate , resulted in significantly higher levels of puerarin in the plasma and tissues, especially in the heart, cerebral cortex, hippocampus and corpus striatum. Overall, these findings collectively supported that puerarin acid esters administration led to greater circulating concentration of puerarin and had a reduced excretion rate, providing significant advantages and theoretical basis for their application in functional foods and pharmaceutical industries.
研究领域:
药物化学
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药理学
·
生物医学工程
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DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Lili Zhang,Chengcheng Duan,Shiquan Feng,Beicheng Zhao,Hailong Li,Xi Zhang,Yan Zhou,Zhenmiao Qin
Background Puerarin (Pue) is an isoflavone compound with significant therapeutic effect on cardiovascular diseases, but its poor water solubility and low oral bioavailability limit clinical application. Methods In this study, Pue was prepared into PLGA nanoparticles (Pue-PLGA NPs) by emulsion solvent volatilization method. The morphology, particle size, Zeta potential, X-ray diffraction (XRD), and fourier transform infrared (FTIR) of the NPs were characterized. Additionally, their stability and in vitro release were evaluated. SD rats were orally administered wtih Pue and Pue-PLGA NPs, and a high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established to determine the concentration of blood samples and to investigate the pharmacokinetic behaviour of Pue and Pue-PLGA NPs in rats. Results The NPs were observed by transmission electron microscopy (TEM) as regular spheroids and uniformly dispersed. The average particle size of the NPs was (167.1±5.26）nm, the Zeta potential was (-29.88±2.46)mV, the encapsulation rate was (83.12 %±4.73 %) and the drug loading capacity was (7.75 %±1.81 %). The results of in vitro release showed that the drug was released slowly and continuously from the NPs, reaching the release platform in 24 h, and the cumulative release amount was (88.55±2.86) %. The pharmacokinetic results showed that the AUC 0–24 , AUC 0-∞ , C max , T max , t 1/2 , MRT 0–24 and MRT 0-∞ of Pue-PLGA NPs were 2.196, 1.978, 1.327, 1.5, 1.385, 3.915 and 3.140 times of Pue, respectively. The relative bioavailability was (197.82±25.28) %. Conclusion These results indicated that the prepared nanoparticles had small particle size, high encapsulation rate, drug loading capacity and good slow-release effect, and could significantly improve the oral bioavailability of Pue in rats.
研究领域:
药剂学
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药物递送系统
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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
APPLIED ORGANOMETALLIC CHEMISTRY
·
2025
·Vol. 39
·期 6
·e70227
·
IF 0
Safdar Ali Amur,Quratulain Khuhro,Najaf Ali Soomro,Muhammad Tariq,Hao Liang,Khalid Hussain Thebo,Mohsin Kazi
This study reports a green one-pot synthesis of glabridin-loaded Zeolitic Imidazolate Framework-8 (Glab@ZIF-8) drug delivery system (DDS) with exceptional drug loading encapsulation (DLE) of ≈ 98.7% and drug loading capacity (DLC) of 32%, surpassing values reported in previous ZIF-8-based DDS. Characterizations using Fourier-transform infrared (FTIR), UV–Visible spectroscopy, dynamic light scattering (DLS), and X-ray diffraction (XRD) confirmed successful encapsulation of Glab within ZIF-8 while preserving its crystallinity. Glab@ZIF-8 exhibited a hexagonal morphology with increased particle size (138.6 ± 5.4 nm) and a higher zeta potential (+41.9 mV), suggesting enhanced colloidal stability and efficient drug entrapment. Thermogravimetric analysis (TGA) demonstrated a total of 32.1% decomposition of Glab@ZIF-8 up to 644 °C. Antibacterial assays revealed that Glab@ZIF-8 exhibited superior activity against Staphylococcus aureus (inhibition zone: 26.2 ± 0.3 mm) and Escherichia coli (23.3 ± 0.2), comparable to that of ampicillin. The minimum inhibitory concentration (MIC) was determined to be 32.5 μg/100 μL. Furthermore, the time-kill studies confirmed a dose- and time-dependent antibacterial effects of Glab@ZIF-8. In vitro drug release studies showed strong pH- and temperature-responsive behavior, with a cumulative release of 93.7% ± 2.4% release at pH 5 (at 37°C) over 72 h. The Glab@ZIF-8 system thus combines high drug loading efficiency, excellent antibacterial activity, and tuneable release characteristics, highlighting its potential as a promising DDS for combating drug-resistant infections.
研究领域:
药剂学
·
微生物学
·
材料科学
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产品关联
DOI
TALANTA
·
2012
·
IF 3.794
Lizhen Liu,Feng Feng,Shaomin Shuang,Yunfeng Bai,Martin M.F. Choi
A rapid and efficient capillary zone electrophoresis (CZE) method with ultraviolet detection has been successfully developed for the determination of puerarin in Xinkeshu capsules and biological samples. The optimal CZE conditions were determined to be 70 mM H 3 BO 3 –Na 2 B 4 O 7 , pH 9.2, injection time 5 s, applied voltage 25 kV, working temperature 25 °C and detection wavelength 254 nm. Under these conditions, a linear range from 17.3 to 138 μg/mL with the correlation coefficient of 0.9998 and limit of detection of 34.6 ng/mL ( S / N = 3) for puerarin were obtained. The relative standard deviation of the migration time and peak area of puerarin were 0.23–0.91, 0.43–1.62, 0.10–0.64 and 0.64–1.32% for intra-day and inter-day analyses, respectively. Satisfactory results were obtained for recovery and repeatability. The proposed method was successfully applied to analyze the puerarin content in Xinkeshu capsules and some biological samples with good results. It is suitable for applications in pharmaceutical industries for quality control and in clinical laboratories for therapeutic drug monitoring purposes.
研究领域:
药学分析
·
生物分析化学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 2
·709
·
IF 4.9
Seungmee Lee,Hyeonmi Shin,Jihyun Bae,Taek Lee,Minji Kim,Heung Bae Jeon,Kang Hyun Lee,Hah Young Yoo,Chulhwan Park
Puerarin is a flavonoid known as a natural antioxidant found in the root ofPueraria robata. Its antioxidant, anticancer, and anti-inflammatory effects have attracted attention as a potential functional ingredient in various bioindustries. However, puerarin has limited bioavailability owing to its low lipid solubility and stability. Acylation is proposed as a synthesis method to overcome this limitation. In this study, lipase-catalyzed acylation of puerarin and various acyl donors was performed, and the enzymatic synthetic condition was optimized. Under the condition (20 g/L of Novozym 435, palmitic anhydride, 1:15, 40 °C, tetrahydrofuran (THF)), the synthesis of puerarin ester achieved a significantly high conversion (98.97%) within a short time (3 h). The molecule of the synthesized puerarin palmitate was identified by various analyses such as liquid chromatography–mass spectrometry (LC–MS), Fourier-transform infrared spectroscopy (FT-IR), and carbon-13 nuclear magnetic resonance (13C NMR). The lipid solubility and the radical scavenging activity were also evaluated. Puerarin palmitate showed a slight decrease in antioxidant activity, but lipid solubility was significantly improved, improving bioavailability. The high conversion achieved for puerarin esters in this study will provide the foundation for industrial applications.Keywords:antioxidant;flavonoid;puerarin;flavonoid ester;lipase;lipid solubility
研究领域:
生物化学
·
制药工程
✓ 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）