SAUDI PHARMACEUTICAL JOURNAL
·
2022
·
IF 4.562
Ge Ou,Qian Li,Lin Zhu,Yuanyuan Zhang,Yijing Liu,Xin Li,Lina Du,Yiguang Jin
Armodafinil inclusion complex (AIC) hydrogel was prepared and evaluated for its therapeutic effect on Post-traumatic Stress Disorder (PTSD). After computer simulation and physicochemical property investigation, the AIC was formed by lyophilization of armodafinil with ethanol as solvent and hydroxypropyl-beta-cyclodextrin (HP-β-CD) aqueous solution, in which the molar ratio of armodafinil and HP-β-CD was 1–1. The AIC encapsulation efficiency (EE) was (90.98 ± 3.72)% and loading efficiency (LE) was (13.95 ± 0.47)% and it increased the solubility of armodafinil in aqueous solution to 21 times. AIC hydrogel was prepared by adding AIC to methylcellulose (MC) hydrogels (3.33% w/v), and its higher drug release amount and slower release rate were testified by the in-vitro release assay and the rheological test. The mucosa irritation of AIC hydrogel was also evaluated. Healthy group, Model group, Sertraline group with 30 mg/kg sertraline gavage, AIC Hydrogel group with 20 mg/kg AIC hydrogel intranasal administration and AIC Aqueous Solution group with 20 mg/kg AIC aqueous solution gavage were set up for the treatment of mice with PTSD generated from foot shock method. Based on freezing response test in fear-conditioning box and open field test, compared with other groups, PTSD mice in AIC Hydrogel group showed significant improvement in behavioral parameters after 11 days of continuous drug administration and 5 days of drug withdrawal. After sacrifice, the plasma CORT level of PTSD mice in AIC Hydrogel group was elevated compared to Model group. Besides, the western blot (WB) of hippocampal brain-derived neurotrophic factor (BDNF) and amygdala dopamine transporter (DAT) immunohistochemistry sections indicated that AIC hydrogel had a protective effect on the brain tissue of PTSD mice. The brain targeting of intranasal administration was evaluated by fluorescence imaging characteristics of Cy7 hydrogel in the nasal route of drug administration, pharmacokinetics and in-vivo distribution of armodafinil. In short, AIC hydrogel is a promising formulation for the treatment of PTSD based on its high brain delivery and anti-PTSD effect.
研究领域:
药剂学
·
神经科学
·
精神医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Electrochemical Science
·
2024
·
IF 1.3
Hui Yang,Xiaoqin Xu,Bichao Shu
A highly sensitive and selective molecularly imprinted polymer-based electrochemical-surface plasmon resonance (MIP-based EC-SPR) sensor was developed for the determination of modafinil in saliva samples. The optimal MIPpy film was synthesized using a modafinil concentration of 1 mM and a constant potential electropolymerization method. The fabricated sensor exhibited a wide linear range (0.1 μM to 10 μM), low detection limits (LOD: 50 nM, LOQ: 170 nM), and high selectivity towards modafinil, with selectivity coefficients of 8.5, 6.2, and 12.7 for adrafinil, armodafinil, and caffeine, respectively. The sensor also demonstrated excellent reproducibility (RSD: 4.2 %) and long-term stability (92 % response after one month). Furthermore, the applicability of the sensor in real samples was validated using spiked saliva samples, with recovery values ranging from 94.7 % to 103.5 %. These results highlight the potential of the MIP-based EC-SPR sensor as a powerful tool for the rapid, sensitive, and selective detection of modafinil in complex biological matrices.
研究领域:
分析化学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Siqing Zhu,Shouguo Zhang,Lulu Pang,Ge Ou,Lin Zhu,Jinqiu Ma,Ruiteng Li,Yijing Liu,Lin Wang,Lifeng Wang,Lina Du,Yiguang Jin
Armodafinil is typically used in clinical practice to maintain cognition and wakefulness in patients suffering from sleep deprivation. However, its poor water solubility and large dosage limit its effective application. Herein, we formulated armodafinil in a nanocrystal hydrogel (NCsG) with appropriate fluidity and viscosity, capable of rapidly dissolving after staying in the nasal cavity for > 4 h and then penetrating the mucosa as quickly as possible in vitro . We found that armodafinil NCsG was biologically safe, as it had no visible ciliary toxicity, as well as extremely stable due to the existence of intermolecular hydrogen-bonding forces. Nasal administration of armodafinil NCsG proved to be more efficient and targeted than oral administration due to its preferential absorption in plasma and more-concentrated distribution in the brain. In addition, compared with the model group, sleep-deprived rats treated with NCsG undergoing Morris water maze (MWM) behavioral experiments had shorter escape latency and much more shuttle times across the platform. Meanwhile, in the open-field test (OFT), these same rats had longer periods of movement in the center, longer time spent upright, and lower anxiety, which clearly demonstrated improved cognitive awareness and wakefulness after intranasal administration. Moreover, we speculated that armodafinil NCsG had a protective effect on hippocampal neurons in Cortical Area 1 (CA1), which is closely related to cognitive function, by upregulating brain-derived neurotrophic factor (BDNF) protein expression. Consequently, the intranasal administration of armodafinil NCsG could serve as a promising integrated-control measure for sleep deprivation.
研究领域:
药理学
·
神经科学
·
药物递送系统
·
行为科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2021
·Vol. 178
·期 24
·4808-4825
·
IF 8.74
Yan-Fei Yang,Hui Dong,Yan Shen,Lei Li,Michael Lazarus,Wei-Min Qu,Zhi-Li Huang
Background and Purpose Modafinil is a potent eugeroic (wakefulness-promoting) drug that is prescribed to treat narcolepsy and has a low incidence of abuse. Although previous studies have shown that modafinil-induced arousal depends on the dopamine receptors and transporters, the specific part/s of the dopamine transmitter system underlying this mechanism remained unclear. Here, we investigated the role of mesencephalic dopamine neurons in modafinil-evoked arousal. Experimental Approach A dopamine indicator (dLight1.1) was employed to detect dopamine changes in the nucleus accumbens (NAc) and dorsal striatum. We specifically lesioned mesencephalic dopamine neurons via diphtheria toxin (DTA) in the dopamine transporter (DAT)-Cre mice. Then, the sleep–wake states were recorded to evaluate the effect of modafinil on arousal. Finally, the extent of DTA-induced lesions was determined by immunohistochemistry. Key Results Modafinil promptly increased dopamine levels in the NAc and dorsal striatum in a dose-dependent manner. Lesioning of dopamine neurons in the substantia nigra pars compacta (SNc) or ventral tegmental area (VTA) had no significant effects on physiological sleep–wake cycles. Modafinil at 90 mg·kg −1 increased continuous wakefulness for 355 min in control mice. However, these effects were slightly decreased by 6.7% in the SNc-lesioned mice and were prominently diminished by 32.8% in VTA-lesioned mice. Furthermore, the modafinil-induced arousal was completely blocked in the SNc-VTA-lesioned mice, whereas lesions of the dorsal raphé nucleus had no effect. Conclusion and Implications Taken together, our findings indicate that mesencephalic dopamine neurons are essential for modafinil-induced arousal. Graphical
研究领域:
神经科学
·
药理学
·
睡眠医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF INORGANIC BIOCHEMISTRY
·
2021
·
IF 4.155
Yucui Jiang,Saixing Liu,Qipeng Yuan,Hao Liang
Acidophilic enzymes play an important role in special industrial catalytic reactions. In this work, we reported Zr-based acid-stable nucleotide coordination polymers (CPs) for efficiently improving acidophilic enzymes immobilization . Among all tested metal ions , the Zr 4+ /AMP CPs exhibited the highest acid stability and enzyme affinity. As a typical acidophilic enzyme, the immobilized Chloroperoxidase by Zr 4+ /AMP CPs displayed robust reusability in the asymmetric synthesis of modafinil, remained 95.7% of conversion rate and 99.1% enantiomeric excess (e.e.) value. This work displayed a novel acid-stable bioorganic and inorganic hybrid nanomaterial for acidophilic enzymes immobilization.
研究领域:
材料科学
·
生物催化
·
酶工程
·
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）