AAPS PHARMSCITECH
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2020
·Vol. 21
·期 8
·1-11
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IF 2.401
Su Yanping,Lu Wenxiang,Fu Xiaoling,Xu Ying,Ye Lixiang,Yang Jian,Huang Huihui,Yu Changxi
The aim of this study was to develop a suitable drug-in-adhesive patch for transdermal delivery of koumine. Acrylic polymer Duro-Tak® 87-4287, which contains hydroxyl groups, may significantly enhance the skin permeation of koumine from transdermal patches containing 0.93–3.72% koumine. Among permeation enhancers, 10% azone showed the greatest potential and increased the flux of koumine to 1.48-fold that of the control. Therefore, an optimized patch formulation containing 3.72% koumine and 10% azone in Duro-Tak® 87-4287 that offers good physical properties was selected for an in vivo pharmacokinetic study using rats. The maximal plasma drug concentration ( C max ) of koumine after transdermal administration (4 mg/patch) was 25.80 ± 1.51 ng/mL, which was in the range of those after oral administration (3 mg/kg and 15 mg/kg). The time to the maximal concentration ( T max ) and the half-life ( t 1/2 ) of the drug with transdermal administration were 3.96 ± 0.46 h and 21.10 ± 1.36 h, respectively, which were longer than those with oral administration. Furthermore, the area under the concentration-time curve (AUC 0–72 h ) of 898.20 ± 45.57 ng·h/mL for the transdermal patch was much higher than that for oral administration (15 mg/kg). In conclusion, the drug-in-adhesive patch containing koumine provides a steady plasma koumine level and sustained release in vivo and can be an effective means of transdermal delivery for koumine.
研究领域:
药学
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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
Journal of Dental Sciences
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2024
·
IF 3.4
Yi Luo,Mengting Duan,Runze Liu,Pei Liu,Wei Fan,Bing Fan
Background/purpose Root canal irrigants are difficult to diffuse deep into the dentinal tubules for root canal disinfection. The purpose of this study was to assess the ability of different diffusing enhancers to deliver chlorhexidine (CHX) into dentinal tubules. Materials and methods The diffusing property of five diffusing enhancers (acetone, DMSO, Triton X-100, JFC-E and azone) into dentinal tubules was firstly assessed using the Rhodamine B. The ability of the diffusing enhancers to deliver CHX into dentinal tubules was then evaluated both qualitatively and quantitatively. A deep dentinal tubule Enterococcus faecalis infection model was further established to test the bactericidal effect of CHX delivered by different diffusing enhancers. Finally, the in vitro cytotoxicity of these diffusing enhancers was tested using the CCK-8 method. Results Azone, Triton X-100 and JFC-E exhibited the largest maximum diffusing depths at all root canal parts ( P < 0.05). Azone group also showed the highest percentage of diffusing depths for all root canal parts, followed by Triton X-100 ( P < 0.05). The percentage of dead bacteria in dentinal tubules close to cementum layer was significantly higher in the CHX + azone group than in the other groups ( P < 0.05), followed by CHX + Triton X-100 and CHX + JFC-E groups. The concentration of CHX diffusing onto the exterior surface of root was significantly higher in CHX + azone group than in the other groups ( P < 0.05). All the diffusing enhancers showed relatively low cytotoxicity. Conclusion Azone showed the highest diffusing ability with low cytotoxicity and might be employed as a carrier agent for either intracanal irrigants or medications to achieve more thorough root canal disinfection.
研究领域:
牙科学
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药学
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微生物学
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毒理学
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产品关联
DOI
PubMed
高影响因子
Burns & Trauma
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2025
·
IF 9.6
Mu Xingrui,Chen Jitao,Zhu Huan,Deng Junyu,Wu Xingqian,He Wenjie,Ye Penghui,Gu Rifang,Wu Youzhi,Han Felicity,Nie Xuqiang
BackgroundDiabetic wounds pose significant clinical challenges due to impaired healing processes, often resulting in chronic, non-healing ulcers. Asiaticoside (AC), a natural triterpene derivative from Centella asiatica, has demonstrated notable anti-inflammatory and wound-healing properties. However, the synergistic effects of nitric oxide (NO)—a recognized promoter of wound healing—combined with AC in treating diabetic wounds remain inadequately explored.MethodsUltra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was utilized to identify differential metabolites and dysregulated metabolic pathways associated with diabetic wounds. Molecular docking analyses were conducted to confirm the binding affinity of AC to key therapeutic targets. The effects of Asiaticoside-nitric oxide hydrogel (ACNO) on gene and protein expression were evaluated using RT-qPCR and western blotting. In vitro experiments using SRC agonists and inhibitors were performed to investigate the impact of ACNO therapy on the expression of SRC, STAT3, and other proteins in HaCaT cells.ResultsMetabolomic profiling revealed that diabetic wounds in mice exhibited marked metabolic dysregulation, which was attenuated by ACNO treatment. Key metabolites modulated by ACNO included mandelic acid, lactic acid, and 3-hydroxyisovaleric acid. The primary metabolic pathways involved were methyl histidine metabolism and the malate–aspartate shuttle. Immunofluorescence staining confirmed that ACNO therapy enhanced angiogenesis, promoted cellular proliferation, and facilitated diabetic wound closure. RT–qPCR data demonstrated that ACNO regulated the transcription of critical genes (SRC, STAT3, EGFR, and VEGFA). Notably, ACNO attenuated SRC/STAT3 pathway activation while concurrently upregulating EGFR and VEGFA expression.ConclusionsThese findings emphasize the therapeutic potential of ACNO hydrogel in diabetic wound healing through the modulation of metabolic pathways and the SRC/STAT3 signaling axis. By correlating altered metabolites with molecular targets, this study elucidates the pharmacodynamic foundation for ACNO’s pre-clinical application and provides valuable insights into the development of targeted therapies for diabetic wound management.
研究领域:
药理学
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代谢组学
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分子生物学
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糖尿病研究
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伤口愈合
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2024
·
IF 4.4
Peng Sun,Hui Li,Kaihua Gong,Yang Zhang,Yu Cai,Chao Liu,Liang Fang
Tandospirone(Tan) is a commonly used drug for anxiety treatment. However, it has a significant first-pass effect and needs to be taken three times a day. To increase the bioavailability of the drug and reduce the number of administrations, this work amid to prepare a Tan patch that can be administered once a day by using the strategy of therapeutic deep eutectic solvent(THEDES) in cooperation with chemical permeation enhancer(CPE). In this study, four organic acids and five permeation enhancers were selected, and the optimized formulation was obtained by single-factor investigation and Box-Behnken design. The optimized formulation could significantly enhance drug loading by 2.5-fold and skin permeation up to 586.6 ± 17 μg/cm 2 in rats. Based on pharmacokinetic results, compared to oral administration, the drug exhibited a substantially elevated bioavailability, registering a 17-fold increase(from 3.01 % to 52.17 %), alongside a 10-fold rise in the mean residence time(MRT). Meanwhile, the patch was not irritating. The results of the mechanistic study showed that levulinic acid(LeA) acted as a bridge to increase the interaction between the Tan and the matrix and inhibited the crystallization of the drug in the patch, and THEDES together with CPE improved the matrix fluidity and skin permeability. This study provides a reference for the joint application of THEDES and CPEs in patch development.
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
BIOORGANIC CHEMISTRY
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2024
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IF 4.5
Yi Chen,Shasha Song,Yongfang Wang,Lili Wu,Jianbing Wu,Zhengmeng Jiang,Xinyu Li
Psoriasis (PSO) is a common inflammatory skin disease caused by multiple factors. Magnolia officinalis is an important medicinal plant in China, with various values such as ecology, medicine, food, and daily chemicals. However, its diverse application potential has not been fully explored. Magnolol (MGO) is the main active compound of Magnolia officinalis with significant anti-inflammatory effect. To investigate the application potential of MGO in inflammatory skin disease, the effects and underlying mechanisms of topical MGO treating psoriasis were explored in this study. Network pharmacology and molecular docking firstly predicted that topical MGO may treat psoriasis by regulating pyroptosis pathway and acting on caspase-1 (CASP1). In vitro experiments then demonstrated that MGO could inhibit the level of inflammatory cytokines and the key protein expression of NOD-like receptor protein 3 (NLRP3)/Caspase-1 pathway in lipopolysaccharide (LPS)-stimulated phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells. Meanwhile, MGO could inhibit CuSO 4 -induced neutrophils migration in Tg (mpx:EGFP) zebrafish by suppressing inflammation and pyroptosis. This study further indicated that topical application of MGO ameliorated imiquimod (IMQ)-induced psoriasis-like dermatitis by reducing the release of inflammatory factors and decreasing the key protein expression of pyroptosis-related NLRP3/Caspase-1 pathway. Metabolomics analysis revealed that topical application of MGO could significantly regulate tryptophan metabolism and affect the level of tryptophan in skin lesions. Tryptophan could also regulate inflammation-related genes and inhibit pyroptosis-related NLRP3/Caspase-1 pathway in LPS-stimulated PMA-differentiated THP-1 cells. In conclusion, this study suggested that topical MGO may ameliorate psoriasis-like dermatitis by inhibiting NLRP3/Caspase-1 pathway and regulating tryptophan metabolism.
研究领域:
药理学
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皮肤科
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分子生物学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
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2024
·
IF 5.3
Yi Chen,Shasha Song,Yongfang Wang,Xiaoli Zhang,Jiafen Zhang,Lili Wu,Jianbing Wu,Xinyu Li
Psoriasis is a common chronic inflammatory skin disease, which has seriously affected human health. Berberine is a plant alkaloid with significant anti-inflammatory effect. In this study, we aimed to determine whether topical application of berberine could ameliorate skin inflammation in psoriasis and explore the potential molecular mechanism. Imiquimod (IMQ)-induced psoriasis-like dermatitis in mice was firstly used to reveal the potential pathogenic mechanism. The transcriptome analysis showed that Janus kinase (JAK)-Signal transducer and activator of transcription (STAT) signaling pathway was significantly enriched in IMQ-induced dermatitis, which included the key genes such as Janus kinase 1 (JAK1), Interleukin-2 (IL2), Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA), Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB) and Signal transducer and activator of transcription 1 (STAT1). Network pharmacology and molecular docking then predicted that topical berberine may treat psoriasis by JAK-STAT signaling pathway, especially act on JAK1, IL2, PIK3CA and PIK3CB. Experimental studies in vivo further demonstrated that topical application of berberine could ameliorate IMQ-induced psoriasis-like skin inflammation by suppressing JAK-STAT signaling pathway. In addition, experimental studies in vitro showed that berberine could directly act on and enter into human immortalized keratinocytes (HaCaT cells). Meanwhile, berberine may inhibit the hyperproliferation and proinflammatory functions of HaCaT cells induced by Interferon-gamma (IFN-γ) via suppressing JAK1/STAT1 signaling pathway. In conclusion, this study suggested that berberine may be a promising topical agent to ameliorate skin inflammation in psoriasis.
研究领域:
皮肤病学
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药理学
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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Pharmaceutics-X
·
2026
·
IF 7.9
Xiaoxing Hang,Taiwei Jin,Jun Hua,Xuenong Zhang,Wenlin Song
Conventional timolol maleate (TM) eye drops are limited by low transdermal bioavailability and short dermal residence time for the treatment of superficial infantile hemangioma (IH). To address this, a novel 0.5% TM-loaded liposomal gel (TM-lipogel) was developed by embedding optimized liposomes within a carbomer gel matrix. The TM-liposomes exhibited a desirable particle size of 139.5 ± 2.1 nm, a polydispersity index (PDI) of 0.051, a zeta potential of −38.7 mV, and an encapsulation efficiency of 64.76 ± 3.2%. Ex vivo permeation studies revealed a 1.9-fold increase in cumulative transdermal delivery compared to the TM-gel, and 4-fold compared to the TM solution ( p < 0.05). Furthermore, confocal laser scanning microscope imaging revealed that TM-lipogel achieved a penetration depth of 400 μm, while the TM-gel and TM-eyedrop only reached 200 μm and 75 μm, respectively, highlighting the superior penetration of the liposomal gel. In a murine xenograft hemangioma model, 0.5% TM-lipogel achieved superior tumor regression (81.09%, p < 0.01 vs. control) compared to 0.5% TM-eyedrop (29.85%) and 0.5% TM-gel (61.69%) by simultaneously downregulating HIF-1α, VEGF, MMP-9 and eNOS. Critically, the optimized formulation exhibited no skin irritation and no systemic toxicity. These findings highlight that the TM-lipogel provides enhanced transdermal delivery with deeper tissue penetration, representing a highly effective and safe transdermal strategy for IH therapy.
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产品关联
DOI
PubMed
高影响因子
ACS Sensors
·
2026
·
IF 10.9
Weizhuo Gao,Chuanyu Zhang,Hongcheng Xu,Xifeng Sun,Xiaoke Lu,Jing Zhang,Wanheng Zhou,Kun Wei,Hao Sun,Weixuan Jing,Zhuangde Jiang,Xueyong Wei
Biomolecular point-of-care monitoring in saliva, urine, and sweat pioneers the real-time and noninvasive biochemical analysis for personalized healthcare and precision disease therapeutics. However, the adoption of these technologies still faces challenges due to the hardly detectable targets with weak redox activity, extremely low analyte concentration, operational instability of sensors, and low scalability of the fabrication process. To address these issues, we proposed a novel core-shell multifunctional particle for the light-enhanced detection of testosterone at the nanomolar level. The particle comprises a ZnIn2S4/SiC core and a targeted molecularly imprinted polymer shell, achieving multifunctions, including visible light sensitivity, testosterone recognition, and redox activity. The printable ability of the multifunctional particle leads to inkjet-printed testosterone sensors with stable (over 50 days), reproducible, and outstanding light-promoted sensing performance (limit of detection 0.01 nM (S/N = 3) and linear range from 0.01 to 1000 nM). The effectiveness of the testosterone sensors was validated in saliva and urine lateral flow electrochemical testing strips and wearable sweat testosterone sensors, achieving testosterone point-of-care testing in multiple human biofluids. These offer great opportunities for the noninvasive biomolecular profiling, further promoting personalized healthcare and precision disease therapeutics.
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产品关联
DOI
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2025
·
IF 2.2
Jie Wang,Xuemei Gu,Xia Gao,Huifang Gao,Jing Chen,Zhiyang Lv,Lei Chen,Yunzhu Xu,Xialin Chen,Liang Cao,Zhenzhong Wang,Jinzhou Tian,Wei Xiao
Objective Gastrodin (GA) and ferulic acid (FA) are the main active ingredients of the traditional Chinese medicine Da Chuan Xiong formula for migraine treatment. This study aimed to develop a gastrodin-ferulic acid co-loaded liposomal gel patch (GA/FA-Lip-GelP) as a transdermal drug delivery system (TDDS) for migraine management.Significance TDDS overcomes the limitations of first-pass metabolism associated with oral administration and is particularly suitable for migraine patients experiencing nausea and vomiting. The system contains three key components: sodium polyacrylate (hydrophilic gel matrix), laurocapram (Azone, permeation enhancer), and GA/FA-loaded liposomes (nanocarrier). This combination enables effective systemic drug delivery.Methods The GA/FA-Lip was prepared using central composite design optimization. Subsequently, the GA/FA-Lip-GelP formulation was developed through single-factor screening and Box-Behnken designs. The optimized GA/FA-Lip-GelP was systematically evaluated via in vitro release studies, ex vivo transdermal permeation experiments, and in vivo pharmacokinetic/pharmacodynamic analyses.Results The GA/FA-Lip was prepared via thin-film dispersion, forming uniform spherical nanoparticles (146.34 ± 1.35 nm). These nanoparticles achieved high encapsulation efficiencies (GA: 85.26 ± 1.90%; FA: 86.92 ± 2.23%) and demonstrated excellent stability. The final GA/FA-Lip-GelP demonstrated optimal adhesion, sustained drug release, and content uniformity under low-temperature storage. Compared to oral administration and non-liposomal gel patches, GA/FA-Lip-GelP showed significantly enhanced transdermal permeation, improved pharmacokinetic profiles, and superior therapeutic efficacy.Conclusions GA/FA-Lip-GelP demonstrated potential as an effective migraine treatment by overcoming first-pass metabolism, thereby improving bioavailability and enabling sustained drug release.
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Ding Zhang,Boqi Chen,Qingke Mu,Wei Wang,Kaili Liang,Liyan Wang,Qing Wang
Anti-cutaneous melanoma activity of the skin-delivered gambogic acid (GA) has been reported in our previous study. However, it is difficult for GA to diffuse passively through intact skin without any enhancement means. In this study, a combination of chemical enhancers (EN: azone and propylene glycol) and physical ultrasound (US) was used to improve the percutaneous permeation of GA and enhance the anti-melanoma activity. The enhancement effect of the combination of EN and US (EN-US) on GA in vitro and in vivo was studied, and the enhancement mechanism and skin irritation were also evaluated. We showed that the parameters of US application at a constant frequency (30 kHz) with a duty cycle of 100% and intensity of 1.75 W/cm 2 for 20 min were optimal. In vitro , EN-US showed a considerable enhancement of the permeation of GA, and the enhancement effect was stronger than that with the use of EN or US alone. In vivo antitumor study showed that the tumor growth was significantly inhibited after percutaneous administration of GA by EN-US, more than in the intravenous injection group. The penetration enhancement mechanism revealed that EN-US not only altered the structure of lipid bilayers and keratins to reduce the barrier effect of the stratum corneum but also produced diffusion channels in the skin under the cavitation effect of US, thereby promoting the skin penetration of GA. In addition, there was no observable skin irritation in mice after treatment with EN-US. Our study demonstrated that the combination of EN and US improved the skin permeation and retention of GA to enhance the anti-melanoma activity. This method also provides technical guidance for the future development of topical and transdermal therapeutic system of GA.
研究领域:
药理学
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肿瘤学
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皮肤病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Dong Jiang,Huajin Tan,Rujiao Zhang,Kaikang Wang,Yujia Zhang,Xiaochuan Tan,Wensheng Zheng
Background Pediatric pulmonary arterial hypertension (PPAH) is a malignant progressive rare disease characterized by restricted pulmonary artery blood flow and progressively increasing blood pressure, which has shorter survival time of only about 10 months as compared to adults. Previous studies have shown that low-dose vardenafil hydrochloride (Var) could significantly improve the symptoms of PPAH. However, Var is currently available only in tablet form in the market for erectile dysfunction , and no special preparation is available for PPAH. Methods In this study, borneol-mediated vardenafil hydrochloride patch (BO-VarP) with sodium polyacrylate as the skeleton material was prepared by coating method, which was characterized by temperature resistance, formability, adhesive force, skin irritation and in vitro permeation. Blood concentration of optimized BO-VarP was measured by LC-MS/MS using intragastric administration (i.g.) as a control, and pharmacodynamic studies were conducted using a rat model of pulmonary arterial hypertension induced by monocrotaline . Results and discussion Optimized BO-VarP showed good appearance, with optimal temperature resistance and formability, appropriate adhesive force and low skin irritation, and its cumulative permeation flux was 14.9 times higher than patch without penetration enhancer . The blood concentration within therapeutic window of BO-VarP lasted longer than i.g., and BO-VarP could improve symptoms of PPAH by reducing pulmonary arterial pressure and right heart hypertrophy index. Conclusion BO-VarP had good therapeutic effect in PPAH rats and suitable compliance in children, which provided a potential industrial transdermal delivery system for the treatment of PPAH.
研究领域:
药理学
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儿科医学
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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
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2020
·
IF 2.997
Ding Zhang,Wei Wang,Tao Hou,Yanjun Pang,Chao Wang,Shuai Wu,Qing Wang
Cutaneous melanoma is the deadliest form of skin cancer, and gambogic acid (GA) exhibits potent anti-melanoma activity. However, clinical application of GA via intravenous injection and oral administration is limited by systemic toxicity and rapid metabolism in the blood. Here, we developed a new, topical route of GA delivery for anti-melanoma activity and reduction of systemic toxicity. The results indicated that the barrier of the stratum corneum (SC) and low diffusion of GA in the hydrophilic viable skin (epidermis and dermis) limited the GA penetration through intact skin. The combination of azone (AZ) and propylene glycol (PG) showed obvious synergistic effects on skin penetration by GA via improving the permeability of the SC and greatly increasing the skin accumulation of GA, thereby forming a high drug concentration in the skin and achieving a topical targeted treatment of melanoma . In addition, GA (AZ–PG) achieved the same anti-melanoma effect via topical delivery as via intravenous injection. Intravenous injection and oral administration of GA induced remarkable pathological changes in various organs in mice, whereas GA was not toxic to various organs or to the skin via topical delivery. These findings indicated that topical administration of GA is an alternative route for melanoma treatment.
研究领域:
肿瘤学
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药理学
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皮肤病学
✓ 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）