Current Pharmaceutical Analysis
·
2023
·Vol. 19
·期 6
·511-520
·
IF 0.6
Zhang Mengmeng,Zou Qiaogen
Background: Atopic dermatitis (AD) is an allergic skin disease that can be inherited. Crisaborole is a specific drug developed to deal with this disease. The compounds of 4-(4- Bromo-3-formyl-phenoxy)-benzonitrile and 4-(4-(4-bromo-3-formylphenoxy)-3- formylphenoxy) benzonitrile
are the representative impurities in the synthesis of Crisaborole active pharmaceutical in gradient (API). Owing to the genotoxic impurities that could lead to cancer and gene mutations, it is necessary to develop a simple, efficient, sensitive, and accurate method to detect these impurities.
In this study, the 4-(4-Bromo-3-formyl-phenoxy)-benzonitrile and 4-(4-(4- bromo-3-formylphenoxy)-3-formylphenoxy)benzo- nitrile present in Crisaborole API were detected using UPLC-MS/MS. Methods: The separation was made on a ZORBAX Eclipse XDB-Pheny column (4.6 mm ×75mm, 3.5
μm) with the mobile phase of acetonitrile solution containing 0.1% trifluoroacetic acid (A) and water containing 0.1% formic acid (B) in gradient elution mode. Quantification was performed using positive ion electrospray ionization (ESI), and the contents of two compounds were determined
using the multiple reaction monitoring (MRM) modes. Results: The quantitative analytical method was fully validated with respect to linearity (r > 0.9998), sensitivity, precision, accuracy (the average recovery of two impurities was 84.1% to 90.7%), and robustness. Conclusion:
Three batches of samples were detected by UPLC-MS/MS, indicating that the proposed approach was applicable for the quality evaluation of Crisaborole.
研究领域:
药物分析
·
皮肤病学
·
毒理学
✓ 已验证
DOI
高影响因子
Frontiers in Microbiology
·
2025
·
IF 4.5
Yinuo Zou,Lei Yu,Jinjing Xue,Tianqi Fang,Liping Sun,Jianfeng Wang,Minhe Cui,Peng Zhang,Yonglin Zhou
The widespread presence of methicillin-resistant Staphylococcus aureus (MRSA) severely threatens convenient therapeutic options in the postantibiotic era. The use of combinations of existing drugs at this stage may be a viable strategy for dealing with complex drug-resistant MRSA infections. An checkerboard MIC (Minimum Inhibitory Concentration) assay, growth curve assay, bactericidal test and scanning electron microscope (SEM) assays were performed to determine whether crisaborole (AN2728), a PDE4 inhibitor for treating atopic dermatitis (AD), produced bactericidal effect with different antibiotics. Here, we identified (AN2728) produced a significant synergistic bactericidal effect with erythromycin, cefuroxime and rifampicin against different bacterial strains of Staphylococcus aureus (S. aureus), especially MRSA (FIC < 0.5) (p < 0.05). Transcriptome analysis, bacterial biofilm assay and several kit assays revealed that AN2728 could also simultaneously affect the membrane and transporter capacity of MRSA. Moreover, in a mouse skin infection model of MRSA, the combination of AN2728 and erythromycin showed remarkable treatment benefits, as shown by significantly reduced bacterial loading (p < 0.05), pathological lesions of the skin and an obvious anti-inflammatory effect (p < 0.05). To our knowledge, this study is the first to establish that AN2728 can cooperate with antibiotics such as erythromycin to completely kill MRSA and that AN2728 can be used to extend the usage life of different antibiotics to address the inevitability of severe MRSA infection.
研究领域:
微生物学
·
药理学
·
传染病学
·
分子生物学
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DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Gang Li,Pengqi Zhu,Caifang Gao,Ye Cai,Ru Feng,Jinghua Sun,Ruiping Zhang
Vitiligo is a depigmenting autoimmune disease driven by oxidative stress and immune-mediated melanocyte destruction. Current therapies are limited by poor drug permeability, systemic side effects, and insufficient efficacy. Herein, we developed a novel carbomer-based hydroxypropyl-β-cyclodextrin-encapsulated crisaborole/curcumin hydrogel (Cri/Cur@CD-Gel) for combinational transdermal intervention of vitiligo via dual antioxidant and anti-inflammatory pathways. Hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complexation overcame the inherent hydrophobicity of crisaborole (Cri) and curcumin (Cur), significantly enhancing their aqueous solubility, stability, and transdermal permeability. Leveraging its skin-adhesive properties, the carbomer hydrogel matrix enhanced drug retention and enabled sustained release at lesion sites, thereby improving drug bioavailability. In vitro , Cri/Cur@CD, leveraging the solubilizing power of HP-β-CD, restored melanocyte viability under oxidative stress, scavenged ROS, normalized mitochondrial membrane potential, and elevated cAMP levels to enhance melanogenesis and tyrosinase activity. In vivo , Cri/Cur@CD-Gel achieved significant repigmentation in monobenzone-induced vitiligo mice, markedly reducing epidermal ROS, CD8+ T-cell infiltration, and inflammatory cytokines (TNF-α, IL-1β, and IL-6). This study demonstrates that the combination of HP-β-CD-based encapsulation and carbomer hydrogel delivery serves as a potential topical administration platform for co-delivering hydrophobic crisaborole and curcumin, and establishes a promising strategy to alleviate vitiligo, that concurrently addresses oxidative damage, inflammatory responses, and melanocyte regeneration.
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DOI
PubMed
高影响因子
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