CHIRALITY
·
2023
·Vol. 35
·期 4
·247-255
·
IF 2
Yan He,Mengdi Qin,Mo Li,Defu Zhi,Baocheng Tian,Feng Qin
Flurbiprofen axetil (FA) is a prodrug of flurbiprofen (FP), and it is hydrolyzed to the active FP by carboxylesterase in plasma after intravenous injection. The pharmacological action of FP is closely related to its chirality, and S-FP shows better analgesic effects than R-FP. Therefore, it is of great significance to compare the in vivo pharmacokinetic behaviors of R-FP and S-FP. In this study, we designed a sensitive high performance liquid chromatography–tandem mass spectrometry method and used CHIRALPAK-IG3 column for chiral separation to quantify the concentrations of R-FP and S-FP in rat plasma. The results show that this method can accurately and effectively analyze the contents of R-FP and S-FP in plasma. In addition, the systemic exposure was approximately 3.09-folds for the S-FP compared with the R-FP following intravenous administration of the FA to rats at a single dose of 4.5 mg/kg. More importantly, the clearance rate of S-FP is significantly smaller than that of R-FP. Therefore, the development of S-FA injectable emulsion for clinical treatment of postoperative pain is very necessary.
研究领域:
药理学
·
分析化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Baohuan Wu,Jie Feng,Tian Zeng,Qian Guo,Zhiwei Zhang,Chen Ding,Baocheng Tian,Sixiang Sai
Based on the advantages of nanostructured lipid carriers (NLCs) promoting transcorneal penetration and in-situ gel prolonging precorneal retention, this study aimed to develop a thermosensitive NLCs integrated nanohydrogel for enhancing the drug bioavailability of flurbiprofen (FB) after topical ophthalmic administration. FB loaded NLCs (FB-NLCs) and thermosensitive FB-NLCs integrated nanohydrogel (FB-NLCs-Gel) were prepared using the melt-emulsification and cold methods, respectively. The nanohydrogel was optimized by the Central Composite Design method, and the optimum formulation selected was 27.36% and 6.22% (w/v) for P407 and P188 , respectively. The sol–gel transition temperatures of undiluted and diluted by artificial tear fluid (ATF) were 28.5 ± 0.4 °C and 32.8 ± 0.9 °C, respectively. And viscosity tests demonstrated that the prepared nanohydrogel showed the effects of anti-tear fluid dilution. The Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) and cytotoxic tests indicated that the FB-NLCs-Gel formulation was non-irritating. In vivo pharmacokinetic studies showed the AUC (0–6h) of FB-NLCs-Gel was 1.93-fold that of FB-Sol and 1.42-fold that of FB-NLCs, suggesting that FB-NLCs-Gel could significantly enhance the bioavailability of FB in aqueous humor. On topical application against rabbit ocular inflammation, the nanohydrogel exhibited superior therapeutic efficacy over that of the FB solution via inhibiting the level of IL-6, TNF-α and PGE 2 in both aqueous humor and tears. Overall, this work has evidenced that the FB-NLCs integrated nanohydrogel would be a promising candidate for ophthalmic anti-inflammatory therapy.
研究领域:
药剂学
·
眼科
·
生物医学工程
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产品关联
DOI
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2021
·Vol. 44
·期 12
·2474-2482
·
IF 3.645
Liancheng Gu,Fangling Wu,Shutong Yang,Fuxing Xu,Xinhua Dai,You Jiang,Xiang Fang,Shaoning Yu,Chuan-Fan Ding
Enantiomeric drugs are widely used and play important roles in pharmaceuticals. Ion mobility spectrometry coupled with mass spectrometry technology provides a unique method for distinguishing the enantiomeric drugs, enantiomeric identification, and quantitation in the gas phase. In this study, enantiomeric molecules of ibuprofen and flurbiprofen were clearly recognized by forming host–guest complex ions using trapped ion mobility time-of-flight mass spectrometry. Ternary complex ions can be produced easily by electrospray ionization of the mixed solutions of ibuprofen, cyclodextrins, and CaCl 2 , LiCl, or NaCl, as well as flurbiprofen, cyclodextrins, and CaCl 2 . The relative contents of different chiral ibuprofens in a mixed solution were also quantitatively measured. This new method is a simple, effective, and a convenient enantioselective analysis method.
研究领域:
药物化学
·
分析化学
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DOI
高影响因子
CHIRALITY
·
2019
·Vol. 31
·期 6
·457-467
·
IF 1.927
Xing Cui,Qi Ding,Ruo-Ni Shan,Chao-Hong He,Ke-Jun Wu
Flurbiprofen is a kind of nonsteroidal anti-inflammatory drug, which has been widely used in clinic for treatment of rheumatoid arthritis and osteoarthritis. It has been reported that S-flurbiprofen shows good performance on clinic anti-inflammatory treatment, while R-enantiomer almost has no pharmacological activities. It has important practical values to obtain optically pure S-flurbiprofen. In this work, chiral ionic liquids, which have good structural designability and chiral recognize ability, were selected as the extraction selector by the assistance of quantum chemistry calculations. The distribution behaviors of flurbiprofen enantiomers were investigated in the extraction system, which was composed of organic solvent and aqueous phase containing chiral ionic liquid. The results show that maximum enantioselectivity up to 1.20 was attained at pH 2.0, 25°C using 1,2-dichloroethane as organic solvent, 1-butyl-3-methylimidazole L-tryptophan ([Bmim][L-trp]) as chiral selector. The racemic flurbiprofen initial concentration was 0.2 mmol L −1 , and [Bmim][L-trp] concentration was 0.02 mol L −1 . Furthermore, the recycle of chiral ionic liquids has been achieved by reverse extraction process of the aqueous phase with chiral selector, which is significant for industrial application of chiral ionic liquids and scale-up of the extraction process.
研究领域:
药学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2020
·
IF 4.389
Lulu Wu,Kaijun Gou,Xianmou Guo,Yingyu Guo,Muyun Chen,Jinxin Hou,Sanming Li,Heran Li
This study examined the effects of pH and chirality on the release of flurbiprofen (FP)-loaded chiral (L/D) self-assembled mesoporous silica nanoparticles (CSA-L/D-MSNs), which were synthesized using cationic cetyltrimethyl ammonium bromide (CTAB) as a template and chiral modified using L/D-tartaric acids. The morphology and physicochemical properties of the CSA-L/D-MSNs were systemically determined and compared with those of non-functionalized mesoporous silica nanoparticles (MSN). The results showed that the CSA-L/D-MSNs were spherical nanoparticles, and the chirality in the L/D-tartaric acids was successfully imparted to the CSA-L/D-MSNs. FP could be loaded into the CSA-L/D-MSNs and was effectively transformed from the crystalline state to an amorphous state after drug loading due to the finite size effect. The release of FP@CSA-L/D-MSNs was faster than that of FP in a pH 1.2 medium and slower in a pH 6.8 medium, and it was better than that of FP@MSNs in both release mediums. Meanwhile, the FP@CSA-L/D-MSNs exhibited a clearly enhanced pH response because the negatively charged carboxyl groups on their surface induced stronger electrostatic repulsion between FP and CSA-L/D-MSNs. Moreover, the effect of the chiral environment on the release of FP@CSA-L/D-MSNs was further studied by introducing small-molecule chiral additives (L/D-alanine). It was found that the release of FP was inhibited in a chiral environment. Particularly, the CSA-L/D-MSNs began to exert the chiral recognition function, in which the CSA-L-MSN responded to chiral stimuli and enhanced the cumulative release amount from 84.25 %–89.11 % in a pH 6.8-L medium, while the CSA-D-MSN showed a suppressed release in the pH 6.8-L medium. Notably, the CSA-L/D-MSNs exhibited intelligent drug release by both chirality response and pH response, and will provide valuable guidance for the design of drug delivery systems.
研究领域:
药剂学
·
纳米医学
·
材料科学
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产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2022
·Vol. 23
·期 8
·1-15
·
IF 4.026
Gu Donghao,Pan Hao,Xu Shuo,Chen Wenyue,Zhu Renfang,Jiang Wenjing,Pan Weisan
In this study, flurbiprofen (FB) was selected as the model drug, and hyaluronic acid–coated flurbiprofen-layered double hydroxide ophthalmic drug delivery system (HA-FB-LDH) was designed and prepared. In this system, the model drug flurbiprofen was intercalated in layered double hydroxide and coated with hyaluronic acid (HA), so as to prolong the corneal residence time and increase the corneal permeability of the drug. Layered double hydroxide (LDH) was prepared by alcohol-water coprecipitation method. Through single factor investigation, the optimum preparation conditions were obtained as follows: The Mg/Al ratio was 2:1, the reaction pH was 11.0, the hydrothermal reaction time was 24 h, and the hydrothermal reaction temperature was 100°C. Under these conditions, the particle size of LDH was 116.4 ± 0.8 nm, the potential was 42.2 ± 1.2 mV, and a relatively regular crystal structure could be had. Then FB was intercalated into the LDH layer to prepare flurbiprofen-layered double hydroxide (FB-LDH). In the end, HA-FB-LDH was prepared by the stirring-ultrasonic method, in which through prescription screening, the molecular weight of HA was 200–400 kDa and the concentration of HA solution was 1.25 mg·mL −1 , the final particle size of HA-FB-LDH was 185.8 ± 3.3 nm, and potential of − 31.4 ± 0.7 mV. The successful loading of FB and the coating of HA were verified by XRD, FTIR, TGA, TEM, and other characterization methods. The results of in vitro stability experiment indicated that the coating of HA could significantly enhance the stability of LDH in the presence of electrolytes. The in vitro release results suggested that the cumulative release amounts of FB-LDH and HA-FB-LDH within 12 h were 92.99 ± 0.37% and 74.82 ± 0.29% respectively, showing a certain sustained release effect. At the same time, the release mechanism of FB-LDH was preliminarily explored by in vitro release experiment, which proved that the release mechanism of FB-LDH was mainly ion exchange. The results of in vivo ocular irritation experiments demonstrated that the ophthalmic preparation studied in this paper was safe and non-irritating. The results of tear pharmacokinetics in rabbits showed that the area under the curve(AUC), the average residence time (MRT), and the highest concentration (C max ) in tears in the HA-FB-LDH group were 4.43, 4.48, and 2.27 times higher than those in eye drops group separately. Furthermore, the AUC of the HA-FB-LDH group was 1.48 times higher than that of the FB-LDH group. The above results suggested that HA-FB-LDH could improve the precorneal residence time. The results of aqueous humor pharmacokinetics in rabbits indicated that the AUC, MRT, and maximum concentration (C max ) in aqueous humor in the HA-FB-LDH group were 6.88, 2.15, and 4.08 times of those in the eye drop group respectively. Additionally, the AUC and MRT of the HA-FB-LDH group were 1.55 and 1.63 times those of the FB-LDH group separately. These mentioned findings verified that HA-FB-LDH could enhance the corneal permeability of the drug. The fluorescent substance-fluoresce isothiocyanate (FITC) was substituted for FB intercalation in LDH for in vitro tissue imaging study of rabbits, whose results stated clearly that FITC-LDH and HA-FITC-LDH could both prolong the precorneal residence time of drugs, and HA-FITC-LDH could increase the corneal permeability of the drug to a certain extent. To sum up, HA-FB-LDH, which can overcome the shortcomings of low bioavailability of traditional eye drops to a certain degree, is a safe and effective ophthalmic drug delivery system.
研究领域:
药剂学
·
眼科
·
生物材料
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DOI
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2023
·Vol. 37
·期 4
·e5580
·
IF 1.8
Rathnakar Nathi,Leela Prasad Kowtharapu,Siva Krishna Muchakayala,Naresh Konduru
A nonsteroidal drug called flurbiprofen (FBN) has analgesic, anti-inflammatory and antipyretic activity. Currently the determination of FBN in cataplasm does not have any pharmacopeial method. However, the drug substance, tablet and ophthalmic solution formulations do have pharmacopeial methods. The development and validation of an accurate, precise and stability-indicating analytical method for the determination of FBN in cataplasm formulations is reported. The gradient method was employed for the quantification of FBN in the presence of internal standards such as biphenyl. A nonpolar separation phase (C 18 , 250 × 4.6 mm, 5 μm Inertsil column; GL Sciences) was used. The optimal flow rate, column oven temperature, injection volume and detector wavelengths were 1.0 ml/min, 40°C, 20 μl and 245 nm, respectively. Mobile phase A was a mixture of water and glacial acetic acid (30:1 v/v) pH adjusted to 2.20 with glacial acetic acid or 1 m NaOH; mobile phase B was methanol (100%). The gradient elution program was [time (min)/% B]: 5/60, 20/70, 25/70, 30/60 and 40/60. The obtained RSDs for the precision and intermediate precision were 0.7 and 0.5%. The percentage recovery ranged from 99.2 to 100.4%. The linear regression coefficient >0.9996 indicates that all peak responses were linear with the concentration. The sample and standard solutions were stable for up to 24 h on the benchtop and in the refrigerator. The critical peaks were well separated from the generated peaks owing to forced degradation, including diluent and placebo peaks. The method validation data and quality by design-based robustness study results indicate that the developed method is robust and fit for routine use in the quality control laboratory. The proposed method is specific, accurate and precise, and the quality by design utilized the first method for the determination of FBN in cataplasm formulations. Transdermal patches and gels have low extraction capacity and this method is applicable for quantification.
研究领域:
药学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Jiao Xie,Xiaoguang Zhu,Meng Wang,Cheng Liu,Guixia Ling,Peng Zhang
Arthritis exerts a major impact on people's physical health and quality of life. Flurbiprofen axetil (FA), an effective non-steroidal anti-inflammatory drug for arthritis, has been limited due to its poor solubility. To boost therapeutic impact and broaden its applicability, we created FA-loaded liposomes (FA@Lipo) with an EE% of 75% via thin-film hydration sonication. Since joint injections or transdermal patches are typically used to treat arthritis, the former has poor patient compliance and the latter has limited transdermal efficacy. Therefore, considering these two aspects, we concentrated FA@Lipo and mixed it with the microneedle matrix to form FA@Lipo loaded soluble microneedles (FA@Lipo-DMNs), which could break through the skin barrier and deliver drugs effectively while reducing patient pain. In vivo pharmacodynamic experiments indicated that FA@Lipo-DMNs had similar therapeutic efficacy and less pain compared with subcutaneous injection (SC), which improved patient compliance. FA@Lipo-DMNs reduced the swelling and inflammatory factors level (TNF-α, IL-1β) of plantar and ankle joints significantly. Histological evaluation showed that FA@Lipo-DMNs could relieved arthritis effectively. All of these results all demonstrated the bright prospects of FA@Lipo-DMNs in the treatment of arthritis.
研究领域:
药剂学
·
药物递送系统
·
药理学
✓ 已验证
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Jiajia Jia,Maoying Zhang,JiaYing Zheng,Jian Zhang,Ting Fang,Ting Sun,Jinxue Cao,Yuyi Xu,Ji Li,Dongkai Wang
Post-operative pain can hinder post-operative recovery by activating the neuroendocrine stress response to surgery, caused by inflammation. Preemptive analgesia using flurbiprofen preoperatively is a potential treatment option to avoid hyperalgesia and prevent post-operative pain. However, the hydrophobicity and short in vivo elimination half-life of flurbiprofen are limitations. In this study, a strategy is presented for targeting inflammatory microenvironments using bioresponsive nanoparticles that simultaneously alleviate inflammation and inhibit hyperalgesia, effectively managing post-operative pain in rats. Our study demonstrates that flurbiprofen-conjugated hydroxyethyl starch can self-assemble into nanoparticles in water, imparting flurbiprofen with higher solubility in water and a longer half-life. Additionally, these biocompatible flurbiprofen-conjugated hydroxyethyl starch nanoparticles accumulate in the incision. Pathological analysis of nerves indicates that hyperalgesia was effectively inhibited by the preoperative administration of HES-Flurbiprofen nanoparticles in the rat incisional pain model. This hydroxyethyl starch-based nanoparticle system also suggests a promising and straightforward strategy for developing biocompatible and bioresponsive formulations for post-operative pain management.
研究领域:
药学
·
纳米技术
·
疼痛管理
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
ACS Omega
·
2024
·
IF 3.7
Ting Sun,Faxing Zhang,Yuyi Xu,Xiaowei Wang,Jiajia Jia,Lihong Sang,Ji Li,Dongkai Wang,Zhiguo Yu
Nonsteroidal anti-inflammatory drugs (NSAIDs) combined with chemotherapeutic agents for the treatment of colorectal cancer (CRC) are a promising therapeutic strategy. NSAIDs can effectively boost the antitumor efficacy of chemotherapeutic agents by inhibiting the synthesis of COX-2. However, hazardous side effects and barriers to oral drug absorption are the main challenges for combination therapy with chemotherapeutics and NSAIDs. To address these issues, a safe and effective lysine–polydopamine@abemaciclib-flurbiprofen (Flu) codrug nanocrystal (Lys-PDA@AF NCs) was designed. Abemaciclib (Abe), a novel and effective inhibitor of the CDK4/6 enzyme, and Flu were joined to prepare Abemaciclib-Flu codrug (AF) by amide bonds, and then the AF was made into nanocrystals. Lysine-modified polydopamine was selected as a shell to encapsulate nanocrystals to enhance intestinal adhesion and penetration and lengthen the duration time of drugs in vivo. Nuclear magnetic resonance, Fourier transform infrared, Massspectrometry, X-ray photoelectron spectroscopy, Transmission electron microscopy, and drug loading were used to evaluate the physicochemical characteristics of the nanocrystals. In our study, Abe and Flu were released to exert their synergistic effect when the amide bond of AF was broken and the amide bond was sensitive to cathepsin B which is overexpressed in most tumor tissues, thus increasing the selectivity of the drug to the tumor. The results showed that Lys-PDA@AF NCs had higher cytotoxicity for CRC cell with an IC50 of 4.86 μg/mL. Additionally, pharmacokinetics showed that Abe and Flu had similar absorption rates in the Lys-PDA@AF NCs group, improving the safety of combination therapy. Meanwhile, in vivo experiments showed that Lys-PDA@AF NCs had excellent antitumor effects and safety. Overall, it was anticipated that the created Lys-PDA@AF NCs would be a potential method for treating cancer.
研究领域:
药学
·
肿瘤学
·
生物材料学
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产品关联
DOI
PubMed
高影响因子
Nano Research
·
2024
·
IF 9.5
Chu Huaqing,Zhang Yanyan,Yang Yuan,Xue Jiangtao,Li Cong,Zhang Wei,Li Zhou,Zheng Hui
Acute postoperative pain is commonly treated with flurbiprofen (FBP), but conventional delivery methods are suboptimal. This study prepared a new non-burst release microneedles (MNs) using genipin cross-linked gelatin (cGel). By adding varying amounts of genipin to modulate the crosslinking degree of cGel, the drug release behavior of the drug-loaded MNs in the skin can be altered. The crosslinking parameters that meet therapeutic requirements are selected, thus providing rapid and long-lasting analgesic effects. cGel solutions were successfully cross-linked, altering matrix material microstructure, confirmed by scanning electron microscope imaging and fourier transform infrared spectroscopy. MNs demonstrated increasing mechanical strength with higher crosslinking. Drug release rates were rapid initially, then slowed, exhibiting a characteristic of decreased release rates with increasing degrees of crosslinking. In vivo , FBP/cGel MNs significantly reduced allodynia and hyperalgesia post-surgery, with the greatest effect observed at 2–3 h post-surgery, and can maintain analgesia for up to 6 h. Biosafety tests confirmed good biocompatibility. FBP/cGel MNs effectively penetrate the stratum corneum, safely delivering drugs with significant analgesic effects, excellent mechanical properties, and good biocompatibility, representing a promising strategy for managing acute postoperative pain.
研究领域:
药剂学
·
疼痛管理
·
药物递送系统
·
生物医学工程
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Baohuan Wu,Mengshun Li,Keke Li,Wei Hong,Qingzhi Lv,Youjie Li,Shuyang Xie,Jingtian Han,Baocheng Tian
In treating eye diseases, topical administration on the ocular surface is the most convenient and acceptable route. However, the intraocular efficiency of non-invasive drug delivery systems is still considerably hampered by the eye’s defense barriers. In this work, cell-penetrating peptide TAT-functionalized, flurbiprofen-loaded liposomes (TAT-FB-Lip) were designed to enable transcorneal drug delivery and prolong ocular surface retention. The corneal penetration-promoting properties of TAT-functionalized liposomes (TAT-Lip) were confirmed in vitro using a corneal permeability assay and the HCE-T cell sphere model and in vivo by aqueous humor pharmacokinetics assessment. TAT-Lip induced an increase in intracellular calcium ion concentration and membrane potential depolarization. F-actin images of HCE-T cells treated with TAT-Lip show the tight junctions between cells partly opened. The cellular internalization pathway mainly depended on the electrostatic interaction between TAT-Lip and the cell membrane, and there is a certain degree of energy dependence. The pharmacokinetics of flurbiprofen in tears demonstrated TAT-Lip could reduce the drug loss rate. Moreover, the anti-inflammatory effect of TAT-FB-Lip was enhanced by markedly suppressing PGE 2 , IL-6, and TNF-α production in tears and aqueous humor in a rabbit conjunctivitis model. In conclusion, this work demonstrates that TAT-Lip is an effective ocular drug carrier system that facilitates transcorneal delivery.
研究领域:
药学
·
眼科学
·
药物递送系统
·
药代动力学
✓ 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）