INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2021
·Vol. 22
·期 8
·4077
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IF 5.924
Xiao-Lei Qiu,Zi-Rui Fan,Yang-Yang Liu,Ding-Fu Wang,Shi-Xin Wang,Chun-Xia Li
A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin inn-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.Keywords:heparin;heparin–phospholipid complex;self-nanoemulsifying drug delivery system;oral absorption
研究领域:
药剂学
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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
FOOD CHEMISTRY
·
2024
·
IF 8.5
Qian Wang,Weiyuan Niu,Xinmiao Wang,Jinghan Yu,Xuan Chen,Dong Cai,Fawen Yin,Xiaoyang Liu,Dayong Zhou
Ethanol evaporation method was applied to synthesize phospholipid complexes from phosphatidylcholine (PC) and short-chain alkyl gallates (A-GAs, a typical representative of lipophenols) including butyl-, propyl- and ethyl gallates. 1 H NMR, UV and FTIR showed that A-GAs were interacted with PC through weak physical interaction. Through the analysis of concentrations of A-GAs and gallic acid (GA) by an everted rat gut sac model coupled with HPLC-UV detection, phospholipid complexes were found to gradually release A-GAs. These liberated A-GAs were further hydrolyzed by intestinal lipases to release GA. Both of GA and A-GAs could cross intestinal membrane. Especially, the transmembrane A-GAs could also be hydrolyzed to produce GA. Undoubtedly, the dual release of phenol compounds from phospholipid complexes of short-chain lipophenols will be effective to extend the in vivo residence period of phenol compounds. More importantly, such behavior is easily adjusted by changing the acyl chain lengths of lipophenols in phospholipid complexes.
研究领域:
生物化学
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药物递送系统
·
食品科学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
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2020
·
IF 6.306
Junhua Li,Yimei Shen,Jiali Zhai,Yujie Su,Luping Gu,Cuihua Chang,Yanjun Yang
This study reported a powder formulation containing omega-3-rich algal oil emulsions stabilized by egg yolk granules (EYGs)/lecithin composites. The improved physical stability of the algal oil samples due to increasing pH and lecithin addition was beneficial to the oxidative stability through analysis of free radical scavenging activities, metal ion chelating activities, and the release of primary and secondary oxidation products during accelerated storage (12 days, 60 °C). In addition, the effect of three antioxidants, i.e. ascorbic acid (VC), ascorbyl palmitate (AP), and α-tocopherol (VE), on lipid oxidation was investigated. Results showed that antioxidant partitioning at different regions of the emulsion system influenced its ability to prevent oxidation with the effectiveness of AP (at the O/W interface) > VE (in the oil phase) > VC (in the aqueous phase). This study developed a new powder-based emulsion formulation for algal oils with superior oxidative stability as an alternative source of omega-3.
研究领域:
食品科学
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生物化学
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产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2022
·
IF 3.915
Ziyi Li,Zhenghua Li,Jianhua He,Jianping Liu
Salvianolic acid B (SAB) is a widely used cardioprotective agent, while its clinical application was limited by poor intestinal absorption and low oral bioavailability. In this study, SAB phospholipid (SP) complex was first prepared to improve the lipophilicity of SAB and then combined with d-glucose to further enhance intestinal absorption. Compared with free SAB, SP or the mixture of SAB and d-glucose, combination of SP and d-glucose showed higher intestinal absorption evidenced by increased effective permeation coefficient (Peff) in the in situ single-pass intestinal perfusion (SPIP) assay. Subsequently, SP and d-glucose at mass ratio of 1:6, with the highest Peff of SAB, were chosen for the preparation of complexed pellets to improve oral absorption efficiency of SAB. As expected, the obtained pellets significantly enhanced oral bioavailability of SAB in the pharmacokinetic study characterized by increasing Cmax and AUC0–t of SAB by 14.88-fold and 5.02-fold than free SAB, respectively. In conclusion, combination of d-glucose in SP pellets can effectively improve the intestinal absorption and oral bioavailability of SAB.
研究领域:
药理学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
·
IF 3.649
Jiao Yu,Kawai Wan,Xun Sun
The skin is an important site for local or systemic application of drugs. However, most of the drugs have poor permeability through the skin’s outermost layer, stratum corneum. The aim of this study was to develop a method to enable transdermal delivery of morin (3, 5, 7, 2, 4-pentahydroxyflavone), which is a poorly water-soluble drug with anti-inflammatory properties obtained from natural products. Morin phospholipid complex (MPC) was prepared and then loaded in Carbopol 940 hydrogel (MPC-gel), which can significantly increase the transdermal flux of morin based on the in vitro skin penetration data presented in this paper. To further enhance permeation, different compositions of penetration enhancers were dispersed in the gel and screened. After applied onto the mouse skin, MPC-gel showed apparent reduction of ear swelling in 2, 4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis (ACD). Further determination of cytokines levels, histopathological analysis and T lymphocytes proliferation indicates that the MPC-gel is potent enough to reduce the inflammatory response mediated by the DNFB in ACD mice model. Collectively, we anticipate that such an approach may provide a new treatment for topical ACD.
研究领域:
药剂学
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免疫学
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皮肤病学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY
·
2025
·
IF 1.8
Qian Wang,Weiyuan Niu,Chuan Li,Xinmiao Wang,Jun Cao,Fawen Yin,Xiaoyang Liu,Dayong Zhou
Butyl gallate (BG, GA-OC 4 H 9 ), dodecyl gallate (DG, GA-OC 12 H 25 ), octyl gallate (OG, GA-OC 8 H 17 ), and hexadecyl gallate (HG, GA-OC 16 H 33 ) were among the alkyl gallates (A-GAs, belonging to phenolic esters) that were used to synthesize phospholipid complexes using an ethanol evaporation method. The everted rat gut sac model (ERGSM) in conjunction with high-performance liquid chromatography-ultraviolet (HPLC-UV) detection illustrated that these complexes were capable of releasing A-GAs (sustained-release behavior 1) in ERGSM, which were later subjected to hydrolysis to produce free gallic acid (GA) (sustained-release behavior 2) that could penetrate mucous membrane of small intestine. The dual-release rate of phospholipid complexes was related to the acyl chain length of A-GAs, and complexes (OG-lecithin from soybean [SL]) with a moderate chain length of 8 exhibited the fastest hydrolysis rate. It was worth noting that unlike complexes containing longer alkyl chains, the BG released by BG-SL could also cross the intestinal mucosa and may undergo hydrolysis to yield GA (sustained-release behavior 2). The behavior of the release of polyphenols from phospholipid complexes means that the retention time of polyphenols in vivo is extended, thereby increasing the extent to which they can be absorbed and utilized by the body. More crucially, the acyl chain lengths of phenolic esters in phospholipid complexes can be readily changed to control such dual-release behavior. Practical applications : Phospholipid complexes of phenolic esters exhibit a good dual-release effect on polyphenols, which can more effectively enhance the bioavailability of polyphenols. By controlling the acyl chain lengths, the number of phenolic hydroxyl groups, and ester bond structures (viz., phenolic acid-COO-C n H 2n+1 or polyphenol-OOC-C n H 2n+1 ), a controlled dual-release behavior of polyphenols from phospholipid complexes of phenolic esters, such as alkyl gallates, will be easily achieved. In view of this, phospholipid complexes of phenolic esters can be potentially utilized as a functional food ingredient.
研究领域:
食品科学
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药理学
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营养学
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产品关联
DOI
高影响因子
Acta Pharmaceutica Sinica B
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2014
·
IF 0
Huiyi Wu,Xiaoying Long,Fei Yuan,Li Chen,Sujing Pan,Yunjun Liu,Yoshiko Stowell,Xiaoling Li
The aim of this study was to develop a formulation to improve the oral absorption of baicalin (BA) by combining a phospholipid complex (PC) and self-emulsifying microemulsion drug delivery system (SMEDDS), termed BA–PC–SMEDDS. BA–PC was prepared by a solvent evaporation method and evaluated by complexation percentage (CP). The physicochemical properties of BA–PC were determined. The synergistic effect of PC and SMEDDS on permeation of BA was studied in vitro with Caco-2 cells and in situ with a single pass intestinal perfusion model. The improved bioavailability of BA in BA–PC–SMEDDS was confirmed in an in vivo rat model. The CP of BA–PC reached 100% when the molar ratio of drug to phospholipid (PP) was ≥1:1. The solubility of BA–PC increased in both water and octanol, and the log P o/w of BA–PC was increased significantly. BA–PC–SMEDDS could be dispersed more evenly in water, compared to BA and BA–PC. Both the Caco-2 cell uptake and single-pass intestinal perfusion models illustrated that transport of BA in BA–PC was lower than that of free BA, while improved significantly in BA–PC–SMEDDS. The relative bioavailability of BA–PC(1:2)–SMEDDS was 220.37%. The combination system of PC and SMEDDS had a synergistic effect on improving the oral absorption of BA.
研究领域:
药剂学
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药物代谢动力学
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产品关联
DOI
PubMed
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Qian Wang,Xinmiao Wang,Dong Cai,Jinghan Yu,Xuan Chen,Weiyuan Niu,Siya Wang,Xiaoyang Liu,Dayong Zhou,Fawen Yin
Phospholipid complexes of alkyl gallates (A-GAs) including ethyl gallate (EG), propyl gallate (PG), and butyl gallate (BG) were successfully prepared by the thin film dispersion method. HPLC-UV analysis in an everted rat gut sac model indicated that A-GAs can be liberated from phospholipid complexes, which were further hydrolyzed by intestinal lipase to generate free gallic acid (GA). Both A-GAs and GA are able to cross the membrane, and the hydrolysis rate of A-GAs and the transport rate of GA are positively correlated with the alkyl chain length. Especially, compared with the corresponding physical mixtures, the phospholipid complexes exhibit slower sustained-release of A-GAs and GA. Therefore, the formation of phospholipid complexes is an effective approach to prolong the residence time in vivo and additionally enhance the bioactivities of A-GAs and GA. More importantly, through regulating the carbon skeleton lengths, controlled-release of alkyl gallates and gallic acid from phospholipid complexes will be achieved.
研究领域:
药理学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2022
·
IF 3.915
Fengmao Zou,Honghui Zhao,Aijinxiu Ma,Danni Song,Xiangrong Zhang,Xu Zhao
To improve the solubility and anti-hyperuricemia activity of the insoluble natural flavonoid isorhamnetin (ISO), an isorhamnetin phospholipid complex (ISO-PC) was prepared. ISO-PC was prepared through solvent evaporation and its prescription process was optimized. The formation of ISO-PC was verified via multiple characterization methods. Parameters such as drug loading, solubility, octanol-water partition coefficient, stability, and in vivo anti-hyperuricemia activity of ISO-PC were investigated. The complexation efficiency of ISO-PC was 95.1% ± 0.56%. The characterization results confirmed that ISO-PC was bound by intermolecular interactions between ISO and phospholipids. Compared with ISO, the solubility of ISO-PC in water and 1-octanol increased by 122 and 16.5 times, respectively. In addition, the octanol-water partition coefficient decreased to 1.08. Pharmacodynamic studies have reported that ISO-PC has a more significant effect on reducing serum uric acid levels and renal protection. In conclusion, the findings of this study suggested that ISO-PC could be used as a promising formulation to improve the solubility and the anti-hyperuricemia activity of ISO.
研究领域:
药学
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生物化学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Yaru Zhang,Wei He,Yawei Du,Ying Du,Chao Zhao,Ying Zhang,Hu Zhang,Lihong Yin,Xinsong Li
Objective The dimeric artesunate phospholipid conjugate (Di-ART-GPC) is a novel amphipathic artemisinin derivative, which can be assembled into liposomes. Di-ART-GPC liposomes were prepared and evaluated as potential anti-inflammatory agents for rheumatic arthritis (RA). Methods Di-ART-GPC was assembled into liposomes utilizing thin film dispersion-high pressure homogenization. Dynamic light scattering (DLS), transmission electron microscopy (TEM), and electron cryo microscopy (cryo-EM) were employed to characterize the liposomal size and morphology. The in vitro cytotoxicity of the Di-ART-GPC liposomes was assessed using Cell Counting Kit-8 (CCK8). The anti-inflammatory effects were studied utilizing the inflammatory cell model. Finally, the in vivo efficacy of the Di-ART-GPC-conjugated liposomes was investigated using the arthritis rat model. Results The particle size of the Di-ART-GPC liposomes decreased to a narrow range of approximately 70 nm following high-pressure homogenization. The in vitro studies revealed low cytotoxicity and good anti-inflammatory effects of the Di-ART-GPC liposomes, which exhibited significantly higher inhibition of the cell secretion of pro-inflammatory cytokines than ART . The in vivo evaluation confirmed that treatment with Di-ART-GPC resulted in a decline in the ankle swelling rate and a low inflammatory response compared with the model control and ART. Conclusion Di-ART-GPC liposomes demonstrate remarkable potential as novel ART-based anti-inflammatory agents for RA.
研究领域:
药理学
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免疫学
·
风湿病学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2016
·
IF 4.32
Jinyang Shen,Jianping Bi,Hongli Tian,Ye Jin,Yuan Wang,Xiaolin Yang,Zhonglin Yang,Junping Kou,Fei Li
Background Akebia saponin D (ASD) exerts various pharmacological activities but with poor oral bioavailability. In this study, a self-nanoemulsifying drug delivery system (SNEDDS) based on the drug–phospholipid complex technique was developed to improve the oral absorption of ASD.Methods ASD–phospholipid complex (APC) was prepared using a solvent-evaporation method and characterized by infrared spectroscopy, differential scanning calorimetry, morphology observation, and solubility test. Oil and cosurfactant were selected according to their ability to dissolve APC, while surfactant was chosen based on its emulsification efficiency in SNEDDS. Pseudoternary phase diagrams were constructed to determine the optimized APC-SNEDDS formulation, which was characterized by droplet size determination, zeta potential determination, and morphology observation. Robustness to dilution and thermodynamic stability of optimized formulation were also evaluated. Subsequently, pharmacokinetic parameters and oral bioavailability of ASD, APC, and APC-SNEDDS were investigated in rats.Results The liposolubility significantly increased 11.4-fold after formation of APC, which was verified by the solubility test in n-octanol. Peceol (Glyceryl monooleate [type 40]), Cremophor® EL (Polyoxyl 35 castor oil), and Transcutol HP (Diethylene glycol monoethyl ether) were selected as oil, surfactant, and cosurfactant, respectively. The optimal formulation was composed of Glyceryl monooleate (type 40), Polyoxyl 35 castor oil, Diethylene glycol monoethyl ether, and APC (1:4.5:4.5:1.74, w/w/w/w), which showed a particle size of 148.0±2.7 nm and a zeta potential of −13.7±0.92 mV after dilution with distilled water at a ratio of 1:100 (w/w) and good colloidal stability. Pharmacokinetic studies showed that APC-SNEDDS exhibited a significantly greater Cmax1 (733.4±203.8 ng/mL) than ASD (437.2±174.2 ng/mL), and a greater Cmax2 (985.8±366.6 ng/mL) than ASD (180.5±75.1 ng/mL) and APC (549.7±113.5 ng/mL). Compared with ASD, Tmax1 and Tmax2 were both remarkably shortened by APC-SNEDDS. The oral bioavailability in rats was enhanced significantly to 183.8% and 431.8% by APC and APC-SNEDDS, respectively.Conclusion These results indicated that APC-SNEDDS was a promising drug delivery system to enhance the oral bioavailability of ASD.
研究领域:
药剂学
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药物代谢动力学
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中药学
✓ 已验证
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2021
·
IF 6.419
Xin-Yi Liu,Wen-Jun Pei,Ye-Zhen Wu,Fang-Li Ren,Si-Yu Yang,Xiu Wang
The aim of this study was to develop and evaluate a triptolide phospholipid complex (TPCX) for the treatment of rheumatoid arthritis (RA) by transdermal delivery. TPCX was prepared and characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR) analysis, transmission electron microscope (TEM), and scanning electron microscope (SEM). The solubility of TPCX was determined. Then, a TPCX cream was prepared to evaluate its percutaneous permeability and the antiarthritis effect. The transdermal permeability was determined using the Franz method, and a microdialysis system was used for skin pharmacokinetic study. A rat model of RA was prepared to evaluate the pharmacological effects. TPCX increased the solubility of triptolide in water, and the percutaneous permeability of TPCX cream was greatly enhanced compared with triptolide cream. The skin pharmacokinetic study indicated that TPCX cream has a longer biological half-life (t1/2) and mean residence time (MRT), but it has a shorter Tmax than that of triptolide cream in vivo. The area under the curve (AUC0–t)/AUC0–∞) and the peak concentration (Cmax) of TPCX cream were obviously higher than those of triptolide cream. The TPCX-loaded cream alleviated paw swelling and slowed down the progression of arthritis by inhibiting the inflammatory response by down regulating the TNF-α, IL-1β, and IL-6 levels, thus exhibiting excellent antiarthritic effects. In summary, the prepared TPCX effectively increases the hydrophilicity of triptolide, which is good for its percutaneous absorption and enhances its effect on RA rats. TPCX can be a good candidate for the transdermal delivery to treat RA.
研究领域:
药理学
·
药物递送系统
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）