International Journal of Pharmaceutics-X
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2026
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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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ACS Sensors
·
2026
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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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DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2025
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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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Drug Delivery and Translational Research
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2023
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IF 5.4
Nan Longyi,Song Haoyuan,Wang Haijun,Mi Ru,Wang Xiaoxu,Fang Liang
The aim of this study was to design a tulobuterol (TUL) patch with good penetration behavior and mechanical properties. Particular attention was paid to the effect of transdermal permeation enhancers on the release process of metal ligand-based acrylic pressure-sensitive adhesive (AA-NAT/Fe 3+ ). The type and dosage of the enhancers were screened by in vitro transdermal penetration in rat skin. The optimized formulation was evaluated in a pharmacokinetic study in rats. Furthermore, the molecular mechanism by which Azone (AZ) improves the release rate of TUL from AA-NAT/Fe 3+ was investigated by FT-IR, shear strength test, rheological study, and molecular simulation. As a result, the optimized formula using AA-NAT/Fe 3+ showed better mechanical properties compared to commercial products. Meanwhile, the AUC 0-t and C max of the optimized patch were 1045 ± 89 ng/mL·h and 106.8 ± 28.5 ng/mL, respectively, which were not significantly different from those of the commercial product. In addition, AZ increased the mobility of the pressure-sensitive adhesive (PSA) rather than decreasing the drug-PSA interaction, which was the main factor in enhancing TUL release from the patch. In conclusion, a TUL transdermal drug delivery patch was successfully developed using metal-coordinated PSA, and a reference was provided for the design of metal-coordinated acrylic PSA for transdermal patch delivery applications. Graphical Abstract
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ACS Applied Materials & Interfaces
·
2023
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IF 9.5
Liuyu Gong,Mathias Bonmarin,Fabrizio Spano,Ya Shen,Lin Shen,Guocheng Han,Shanshan Wei,Qihan Zhang,Zhencheng Chen,Feijun Zhao
The compositions of sweat and blood are related. Therefore, sweat is an ideal noninvasive test body fluid that could replace blood for linear detection of many biomarkers, especially blood glucose. However, access to sweat samples remains limited to physical exercise, thermal stimulation, or electrical stimulation. Despite intensive research, a continuous, innocuous, and stable method for sweat stimulation and detection has not yet been developed. In this study, a nanomaterial for a sweat-stimulating gel based on the transdermal drug delivery system is presented, which transports acetylcholine chloride into the receptors of sweat glands to achieve the function of biological stimulation of skin sweating. The nanomaterial was applied to a suitable integrated sweat glucose detection device for noninvasive blood glucose monitoring. The total amount of evaporated sweat enabled by the nanomaterial is up to 35 μL·cm–2 for 24 h, and the device detects up to 17.65 μM glucose under optimal conditions, showing stable performance regardless of the user’s activity level. In addition, the in vivo test was performed and compared with several studies and products, which showed excellent detection performance and osmotic relationship. The nanomaterial and associated integrated device represent a significant advance in continuous passive sweat stimulation and noninvasive sweat glucose measurement for point-of-care applications.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
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IF 6.51
Jiuheng Ruan,Chao Liu,Jiaqi Wang,Ting Zhong,Peng Quan,Liang Fang
This study sought to provide approach for evaluating and predicting the efficacy and safety of permeation enhancers on the basis of their kinetic distribution behavior in the skin dictated by physicochemical properties. Herein, the efficacy-safety regularity of eight permeation enhancers were studied with ex vivo skin permeation study, small-angle X-ray scattering, MTT assay, H&E staining, and in vivo skin erythema analysis, classifying into the following three categories: high enhancement–low irritation, medium enhancement–high irritation, and low enhancement–low irritation. These three modes were positively correlated with the distribution amount of permeation enhancers in the skin layers and verified by the in vitro tape-stripping study. The kinetic parameter, effective-safety index ( I ES ), was proposed to describe the regularity of enhancement effect tendency and irritation risk, and the relationship between I ES and physicochemical properties of permeation enhancers was analyzed with multiple regression analysis. According to the results of modulated temperature differential scanning calorimetry and dielectric spectrum, permeation enhancers with high lipophilicity and low polarity had I ES > 1, suggesting high enhancement effect and low irritation due to their higher affinity with the stratum corneum (SC) than with epidermis (EP). Permeation enhancers with medium lipophilicity and medium polarity exhibited 0 < I ES ≤ 1, showing medium enhancement effect and high irritation, as determined by their comparable affinity with the SC and epidermis (EP). However, permeation enhancers with low lipophilicity and high polarity had I ES → 0, demonstrating low enhancement effect and irritation, as indicated by their poor affinity with the SC. In summary, different physicochemical properties of permeation enhancers influenced their affinities with skin layers, resulting in their different enhancement effect and irritation potential. This study will provide a theoretical basis and criteria for evaluating and predicting the safety and efficacy of permeation enhancers, which will enable a more rational selection of permeation enhancers in the optimization of transdermal patches .
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Evidence-based Complementary and Alternative Medicine
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2022
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IF 2.65
Yi-qiu Liu,Dandan Zhang,Junyu Deng,Ye Liu,Wei Li,Xuqiang Nie
Diabetic cutaneous ulcers (DCU) are a chronic and refractory complication of diabetes mellitus, which can lead to amputation or even death in extreme cases. Promoting the early healing of DCU and reducing the disability rate and treatment cost are important research topics in treating with integrated traditional Chinese and Western medicine. Centella asiatica total glycosides are extracted from the traditional Chinese medicine Centella asiatica and have angiogenic, anticancer, antioxidant, and wound healing effects. Nitric oxide (NO) is a critical component of wound healing. During the development of DCU, endogenous NO secretion is insufficient. It has been reported that exogenous nitric oxide can promote wound healing, but it is difficult to adhere to the skin because of its short half-life. Therefore, in this study, we used the polymer excipient hydroxyethyl cellulose as the matrix, combined with Centella asiatica total glycosides and NO, and developed a new type of topical gel that can promote wound healing. At the same time, we made a comprehensive research and evaluation on the preparation technology, quality standard, skin toxicity, reproductive toxicity, and pharmacodynamics against diabetic skin ulcers of the gel. According to our research results, the combination of Centella asiatica total glycosides and nitric oxide can accelerate the healing speed of DCU wounds, and 8% Centella asiatica total glycosides nitric oxide gel (CATGNOG) has the best effect in ulcer wound healing. CATGNOG has the advantages of feasible preparation method, controllable quality, good stability at low temperature, and no apparent skin toxicity and reproductive toxicity. It can effectively inhibit the growth of bacteria on the wound surface, relieve the inflammatory reaction of the wound surface, and promote the healing of ulcer wound, which provides a basis for further research of the preparation in the future.
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JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Ye Liu,Jiufeng Zhao,Xingrui Mu,Junyu Deng,Xingqian Wu,Wenjie He,Yiqiu Liu,Rifang Gu,Felicity Han,Xuqiang Nie
Ethnopharmacological relevance Centella asiatica (L.) Urban is an ethnobotanical herb. The main bioactive components of Centella asiatica are pentacyclic triterpenoid glycosides , namely asiaticoside and hydroxyasiaticoside. Asiaticoside possess a diverse array of pharmacological properties, such as wound-healing, anti-inflammatory, antioxidant, anti-allergic, antidepressant, anxiolytic, anti-fibrotic, antibacterial, anti-arthritic, anti-tumor, and immunomodulatory activities. Aim of the study The purpose of this investigation is to explore potential therapeutic interventions for the delayed healing of wounds in diabetic patients (DW) facilitated by Asiaticoside-Nitric Oxide. To clarify the key molecular mechanism of miRNA-21-5p in DW wound repair and to deepen the understanding of DW disease pathogenesis. Materials and methods Firstly, miRNA microarray technology, bioinformatics, and RT-qPCR were used to analyze DW patients' and normal controls' skin tissue samples. Secondly, in order to investigate the role of miRNA-21-5p, a hyperglycemic model was established using HaCaT cells. Overexpressing as well as interfering HaCaT cell lines were constructed by lentiviral infection to further explore the proliferative and migratory effects of Asiaticoside-Nitric Oxide. The next step was to search for potential target genes of miRNA-21-5p and verify them with dual-luciferase reporter assay. Finally, the expression levels of target genes and proteins were detected through the utilization of RT-qPCR and Western blotting under the influence of Asiaticoside-Nitric Oxide. Results A library of miRNAs and target genes expressed explicitly in DW patients and rats was established. The study confirmed the upregulation of miRNA-21-5p in DW patients and identified its involvement in signaling pathways related to chronic ulcer wound repair. Overexpression of LV-miRNA-21-5p significantly promoted cell proliferation , while treatments of Asiaticoside-Low dose (AC-L) and Asiaticoside-Medium dose (AC-M) enhanced proliferation and migration, particularly when combined with nitroprusside (SNP). Further analysis revealed potential target genes of miRNA-21-5p, such as TGF-β1, SMAD7, and TIMP3. Their interaction with miRNA-21-5p was confirmed through dual luciferase assays. The study found that anti-DW drugs increased the expression of TGF-β1 and SMAD7 while inhibiting TIMP3 expression in a high-glucose environment. Conclusions The research concluded that miRNA-21-5p plays a crucial role in the delayed healing of diabetic wounds, and that the combination treatment of AC + SNP shows promise in promoting wound healing in DW rats. Target genes, including TGF-β1, SMAD7, and TIMP3, may contribute to the regulatory mechanisms involved in diabetic wound healing. These findings provide valuable insights for developing novel therapeutic approaches for DW.
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ACS Omega
·
2023
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IF 4.1
Yi Chen,Yongfang Wang,Shasha Song,Xiaoli Zhang,Lili Wu,Jianbing Wu,Xinyu Li
Baicalin (BAI), the main active component of Scutellaria baicalensis, has significant anti-inflammatory and antibacterial effects. Echinacoside (ECH), an active component from Echinacea purpurea, has significant antiangiogenesis and antioxidant effects. In previous studies, BAI or ECH has been used for some skin inflammation problems by topical treatment. Psoriasis (PSO) is a common inflammatory skin disease with typical features such as excessive inflammatory response and vascular proliferation in skin lesions. Because of the anti-inflammatory effect of BAI and the antiangiogenic activity of ECH, it is proposed that the combination of BAI and ECH can ameliorate psoriatic skin lesions better than a single component. This study aims to explore the effects and potential mechanisms of BAI combined with ECH on imiquimod (IMQ)-induced psoriatic skin lesions by topical treatment. Transcriptome analysis first showed that the TNF signaling pathway and the VEGF signaling pathway were significantly enriched in IMQ-induced psoriatic skin lesions. Topical application of BAI combined with ECH could ameliorate IMQ-induced skin lesions in mice, especially the better effects of B2-E1 (BAI/ECH = 2:1). Network pharmacology analysis and molecular docking indicated that BAI-treated PSO on the skin by regulating the TNF signaling pathway, and ECH treated PSO on the skin by regulating the VEGF signaling pathway. Meanwhile, the ELISA test and the qPCR assay showed that BAI combined with ECH could inhibit the expression of key cytokines and genes related to the TNF signaling pathway and the VEGF signaling pathway. Zebrafish experiments demonstrated the anti-inflammatory and antiangiogenic effects of BAI combined with ECH and revealed the potential mechanisms associated with regulating the inflammation-related TNF signaling pathway and the angiogenesis-related VEGF signaling pathway. This suggested that BAI combined with ECH may be a promising topical agent to ameliorate psoriatic skin lesions in the future.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
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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.
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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.
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JOURNAL OF PHARMACEUTICAL SCIENCES
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2020
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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.
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