JOURNAL OF MOLECULAR STRUCTURE
·
2023
·
IF 3.8
Xiaodan Ma,Xinlei Chen,Yaoqi Zhen,Xunjie Zheng,Chengzhe Shi,Shouwen Jin,Bin Liu,Bin Chen,Daqi Wang
Cocrystallization experiments between the widely popular active pharmaceutical ingredient (API) minoxidil and an array of aryl acids coformers were carried out, successfully yielding 8 multi-component samples consisting of 3 co-crystals and 5 salts. Most of them are hydrates. The nature of the samples have been featured by XRD, IR and EA, the melting points were also gauged. The structural and supramolecular aspects are investigated in detail. In all adducts the N-oxide shows various nonbonding contacts. The Hmnd dimer was established at both 1 and 4 by a pair of symmetric N H···O H-bonds. In all cases the minoxidil and coformers were connected by the N H···O/O H···O synthon which is proved to be the highest extensive associates (appearing in 8/8 structures), even in the coexistence of other potentially disruptive non-covalent bonding moieties. Interestingly, the piperidine moieties as effective H-bond acceptor never participated in accepting the H-bonds. The pyrimidine amino also only acts as the H-bond donors. The outcomes unveil that the crystal packing is relied on the strong N H⋯O/O H···O H-bonds. Deep insight into the crystal packing uncovered that a different set of extra O N/O O, CH···C, N H···C, CH···O/CH 2 O, CH CH/CH 2 CH/CH 2 CH 2 , CH 2 Cl, CH 3 -π/CH 2 -π, NH-π, O-π, and π-π contacts contribute to the stabilization and expansion of the total structures. For the synergism of the various nonbonding forces there had the homo/hetero supramolecular synthons. Some classical graph set notations of R 2 2 (9) and R 4 2 (8) were present in the relative high frequency.
研究领域:
药物化学
·
晶体学
✓ 已验证
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2023
·
IF 5
Ying Sun,Yongxiang Zhang,Xiaxia Liu,Yan Tingting,Liyan Shen,Dan Ye,Xia Kong,Yonghui Su,Qingping Tian
Transfersomes is one of the most effective nanotechnology-based formulation for transdermal delivery of minoxidil (MXD), however the potential use was limited by its low drug content ( DC ) and entrapment efficiency ( EE ). In this study, efforts have been made to improve DC and EE of MXD in transfersomes for effective topical treatment of alopecia . By dissolving both MXD and edge activator (Tween 80) in aqueous phase than either or both of them co-dissolving in organic solvent with lipids (phospholipid and cholesterol with mass ratio of 5:1), the DC and EE of MXD transfersomes prepared by thin film hydration method were significantly increased. The optimized transfersomes (MT) and its gel (MT gel ) with mass ratio of drug, Tween 80 and lipids 3:1:18 have a spherical morphology without aggregation, and a particle size of not more than 100 nm. The differential scanning calorimetry measurements revealed that the drug in MT was in the non-crystalline state. MT and MT gel exhibited better in vitro transdermal penetration ability and hair of C57BL/6 mice growth-promoting capacity than commercial formulations. MT gel has non-irritation and is better than MT in skin adhesion, stability, potential for skin storage and hair growth promotion ability, which could endow it to be a promising strategy for topical treatment of alopecia.
研究领域:
药剂学
·
纳米技术
·
皮肤科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2023
·
IF 3.8
Yushu Chen,Shouwen Jin,Yutao Chen,Xingjun Gao,Xusen Gong,Linfang Shi,Hui Liu,Xiaodan Ma,Daqi Wang
In this job eight new multicomponent crystalline systems (including 2 cocrystals + 5 salts) from active pharmaceutical ingredient (API) minoxidil (mnd) and organic acids were successfully prepared via the very common slow solution evaporation method and featured by the structural and spectral characterizations. In these systems the mnd and its partners were coupled through the N-H···O/O-H···O linkages which are authenticated to be the most frequent associates (created in all), even in the coexistence of the other underlying disruptive non-covalent linking fragments. Apart from the N-H⋯O/O-H···O H-bonds, the O-H···N H-bonds were also set up in 1 - 5 and 7 . Close inspection of the crystal pilings uncovered that under the help of an array of subsidiary O···C, O···O, O···N, Cl···O, N···Cl, CH 2 ···C, CH···N, CH···O/CH 2 ···O, CH 2 ···Cl, CH···π/CH 2 ···π, NH···π, O···π, CH···CH 2 /CH 2 ···CH 2 and π···π forces, the systems were stretched into 2D-3D motifs. Significant non-covalent interactions were calculated by means of the Hirshfeld surface analysis for understanding the noncovalent interactions which stabilized the crystal packings. Thanks to the delicate equilibrium of the multiple associates, the homo/hetero synthons or both were set up, here the general R 2 2 (8) graph has appeared with the highest frequency. This work verifies that careful check of the multicomponent systems comprised of various acids for a given API where multiplex molecular impacts struggle to dictate the material structures can engender rich and striking outcomes.
研究领域:
药物化学
·
晶体学
·
超分子化学
✓ 已验证
DOI
高影响因子
Drug Delivery and Translational Research
·
2025
·
IF 5.5
Zhang Min,Pang Xiaoya,Kang Shuhui,Sui Hao,Kong Xia,Wang Gang,Wang Ruixuan,Shen Guiqing,Tian Qingping
Our MXD/SCD@TF designed by the combination of transfersome and inclusion technology was obviously superior to commercial 2% MXD tincture in treating androgenetic alopecia (AGA) in mice, but its complex preparation and poor stability undoubtedly increased both development and usage costs. In this paper, using our previous alcohol-free low surfactant microemulsion technology with VES as auxiliary oil phase, microemulsions loaded with the inclusion complex of MXD and sulfobutylether-β-cyclodextrin (SBE-β-CD) were prepared, optimized and characterized, and the therapeutic effect on AGA C57BL/6 mice was compared with MXD/SCD@TF. According to the ternary phase diagram, steady-state permeation rate of MXD through SD rat skin and drug retention, MXD/SCD@ME was selected as the optimal prescription, composed of 5.25% oil phase, 9.75% surfactants, 10.20% SBE-β-CD, 1.02% MXD and 73.78% water, which conformed to the characteristics of microemulsion. MXD/SCD@ME had good stability, and the application of inclusion technology increased the MXD loading in microemulsion to nearly 5 times. The results of in vivo skin penetration test and laser confocal scanning visualization showed that MXD/SCD@ME was easier to deliver drugs to deeper skin tissues than MXD/SCD@TF. Hair regeneration study demonstrated that MXD/SCD@ME had higher ability than MXD/SCD@TF in promoting hair growth, prolonging hair growth period, reducing ROS level and promoting cell proliferation of hair follicles. In addition, the blank microemulsion of MXD/SCD@ME had certain therapeutic effect on AGA, indicating the synergistic effect between VES and MXD. All these indicated that MXD/SCD@ME is expected to provide a better choice for pharmacological therapy of MXD on AGA than MXD/SCD@TF. Graphical
研究领域:
药剂学
·
皮肤科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2023
·
IF 18.9
Hui Xing,Huanqi Peng,Yuhui Yang,Kai Lv,Shihao Zhou,Xiangjun Pan,Jianjin Wang,Yunfeng Hu,Guowei Li,Dong Ma
Androgenetic alopecia (AGA) is a common clinical condition, affecting over 200 million people globally each year. For decades, Minoxidil (Mi) tincture has been the primary treatment for this disease, but its low utilization rate and significant side effects necessitate new therapeutic strategies. Nitric oxide (NO) is a signaling molecule in various physiological processes, including vasodilation, immune responses, and cell proliferation. Herein, we constructed a hyaluronic acid liposome (HL) complex as a novel transdermal delivery system (HL@Mi/NONOate) for NO and Mi, which displayed promising transdermal and hair-regrowth effects. In-depth mechanistic studies revealed three potential pathways of the synergistic AGA therapy. First, NO promoted capillary dilation and accelerated blood flow, thus achieving efficient penetration of Mi. Due to the structural advantage of liposomes, the residence time of the Mi in the skin was prolonged. Moreover, HL@Mi/NONOate promoted cell proliferation and angiogenesis, and upregulated the expression of regulatory factors involved in follicle stem cell differentiation. In the AGA model, HL@Mi/NONOate down-regulated the expression of inflammatory factors, inhibiting the inflammation of follicle and improving the microenvironment of hair regrowth. Concurrently, HL@Mi/NONOate upregulated the expression of Ki67 and PCNA proteins in follicle tissues, inducing follicle regeneration and development, ultimately achieving the synergistic multimodal AGA therapy.
研究领域:
药学
·
皮肤科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Ziyi Liu,Xiaojuan Li,Sha Xiong,Ting Xiao,Siwen Jiao,Guihong Chai,Yuehong Xu
Androgenic alopecia (AGA), the most prevalent type of progressive hair loss, currently lacks an effective topical treatment regimen. In this study, we synthesized an ionic liquid (IL) to co-solubilize minoxidil (MXD) and finasteride (FIN) and subsequently formulated them into an in situ thermosensitive ionic liquid/cyclodextrin/poloxamer hydrogel (ICPG), termed M + F@ICPG. M + F@ICPG was developed for the transdermal co-delivery of these two drugs, aiming to provide a multipath therapeutic approach for AGA while avoiding the adverse effects commonly associated with oral FIN and topical MXD tincture. The thermosensitive characteristics, skin penetration, hair follicle (HF) targeting efficiency, biosafety, and in vivo therapeutic efficacy of M + F@ICPG were evaluated using an AGA mouse model. Our results demonstrated that M + F@ICPG was a thermosensitive hydrogel, transitioning from solution to gel upon contact with the scalp. Compared to the FIN suspension and MXD tincture, M + F@ICPG significantly enhanced the skin penetration (∼2.2-fold) and retention (∼8.6-fold) of FIN and increased the relative retention of MXD (∼6.3-fold) in the skin. Moreover, M + F@ICPG exhibited a HF targeting index of 1.74 for MXD and 1.46 for FIN, indicating enhanced drug targeting to HF. M + F@ICPG showed superior in vivo efficacy in terms of hair regeneration, anagen recovery, inflammation mitigation, and microvessel reconstruction. The underlying mechanism was attributed to the upregulation of hair growth genes, downregulation of hair loss genes, and reduction of abnormally elevated inflammatory factors. These findings suggest that this novel M + F@ICPG is a promising topical co-delivery system for the synergistic treatment of AGA.
研究领域:
药剂学
·
皮肤科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2025
·Vol. 19
·期 1
·11
·
IF 4.8
Zhiqing Liu,Wenhua Huang,Shanhua Xu,Meilan Nan,Xian Cui,Yue Wang,Zhehu Jin,Wan Meng,Jingbi Meng,Longquan Pi
Background:Topical minoxidil remains the only FDA-approved treatment for hair loss, yet its clinical efficacy is compromised by organic-solvent-induced scalp irritation and poor patient adherence. This study aimed to evaluate natural illite as a carrier for minoxidil and to explore its potential hair-growth-promoting mechanisms.Methods:Thermal–acid-modified illite was engineered as a spray-dried, hydroalcohol-free minoxidil carrier for topical application. Hair regrowth efficacy was assessed in C57BL/6 mice via a 14-day depilation model. Mechanisms were elucidated via RNA-seq, Ki67/TUNEL immunofluorescence, and p-STAT3 immunohistochemistry.Results:Modified illite resulted in a 4.2-fold surface area increase and successful minoxidil loading. The minoxidil/illite formulation demonstrated efficacy equivalent to that of free minoxidil while also eliminating solvent toxicity. Mechanistic analysis revealed that illite functions as an active carrier: both the illite-alone and minoxidil/illite-treated groups exhibited increased Ki67+proliferation and reduced TUNEL+apoptosis. Transcriptomic profiling demonstrated dual mechanisms—enrichment of Myc proliferation pathways and suppression of IL-6 inflammatory signaling (p< 0.001)—with reduced p-STAT3 expression confirmed by immunohistochemistry.Conclusions:These findings suggest that an illite-based carrier can enable topical delivery of minoxidil with preserved efficacy and that illite itself exhibits intrinsic hair-growth-promoting activity via anti-inflammatory and pro-proliferative mechanisms, which may help alleviate adherence barriers associated with conventional topical alopecia therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yingying Liao,Chutong Liu,Lihao Guo,Li Wang,Shuxiang Xu,Gandong Zhou,Shuyi Zhou,Miaomiao Yuan
Androgenetic alopecia (AGA) is one of the most customary inducement of hair loss, and topical minoxidil (MXD) has been widely used to treat AGA, but the drug delivery rate is seriously limited by the poor solubility of MXD and traditional inefficient transdermal delivery methods. Microneedles (MNs) can directly puncture the skin for administration with improved drug delivery rate and weaker side effects. However, the common solid MN is easy to fall off, especially in hairy areas, which reduces the duration of drug action. To ensure robust attachment and prolong the drug efficacy, we designed minoxidil nanoparticle-loaded hyaluronic acid (HA) microneedles and integrated with a switchable temperature-responsive adhesion ring, which polished the solubility of MXD and made the MNs retained in the body for a longer time and improved clinical operability. In AGA model, the MXD NP-loaded MN system could promote the hair follicles transformation from telogen phase to anagen phase. Compared with the application of the traditional minoxidil solution, our MN system can achieve therapeutic effect with a lower dose and frequency, which reduced side effects and advanced user compliance. Therefore, this transdermal delivery system can possibly offer a promising strategy for treating alopecia and other dermatoses.
研究领域:
药剂学
·
皮肤科
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Meirong Yin,Yongnian Zeng,Han-Qing Liu,Wen Zhang,Chenyuan Wang,Chuang Chen,Wei Li
Androgenetic alopecia (AGA) is the most common type of progressive hair loss in both men and women that severely reduces life quality and affects patients’ self-esteem. Due to the shortcomings of traditional therapeutic formulations (e.g., topical minoxidil and oral finasteride), such as low bioavailability, frequent dosing, and significant side effects, there is an urgent need to develop a safe and effective strategy for AGA treatment. Here, we report a water-soluble microneedle (MN) patch integrated with biodegradable minoxidil (MXD)-loaded microspheres for long-acting AGA treatment with reduced administration frequency and improved patient compliance. When the patch pierces the skin, the MNs rapidly dissolve and deliver MXD-encapsulated polylactic-co-glycolic acid (PLGA) microspheres into the skin, which, subsequently act as drug reservoirs for the sustained release of the therapeutics for over 2 weeks. Additionally, the application of the MN patch provided a mechanical stimulation on mouse skin, which was also helpful for hair regrowth. Compared with the topical MXD solutions that have been commercialized on the market and require daily application, the long-acting MN patch contains a much lower drug amount and shows a similar or superior hair regeneration effect in AGA mice while only requiring monthly or weekly administration. These encouraging results suggest a simple, safe, and effective strategy for long-acting hair regeneration in clinics.
研究领域:
药学
·
生物医学工程
·
皮肤科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Yujun Shan,Chang Xu,Yanxia Guo,Le Wen,Shanshan Zhou,Li Fang,Junjun Xu,Hangsheng Zheng
Androgenic alopecia (AGA) represents one of the most prevalent forms of hair loss. Liposomes (LPSs), acting as a localized dermal drug reservoir with sustained release property, can effectively prolong and enhance drug retention within the skin. Minoxidil sulfate (MXS), a potent active metabolite of minoxidil (MX) for promoting hair growth, exhibits instability in aqueous solution and faces difficulties in depositing within the deep dermal hair follicle regions. In this study, MXS-LPSs were fabricated via the thin-film hydration-dispersion method combined with an ammonium sulfate gradient active drug loading process, and their physicochemical characteristics were comprehensively characterized. The skin permeation/deposition properties of the drug from the MXS-LPSs were investigated by Franz diffusion cell method on ex vivo rat skin, and the mechanism underlying the targeted drug delivery of LPSs to hair follicles was explored by confocal laser scanning microscopy (CLSM). The pharmacodynamic evaluation of MXS-LPSs was carried out in AGA model rats. The optimized MXS-LPSs were uniformly dispersed with enhanced stability. The average vesicle size of MXS-LPSs was 129.46 ± 7.04 nm, the z eta potential was −25.57 ± 4.79 mV, the encapsulation efficiency (EE) was 92.72 ± 0.75 %, and the drug loading (DL) was 2.80 ± 0.12 %. The results of ex vivo skin permeation/deposition showed that the cumulative permeated drug amount ( Q n ) from MXS-LPS, MX tincture and MXS solution at 36 h was 225.98 ± 11.53, 19.79 ± 1.97 and 584.42 ± 2.33 μg·cm −2 , respectively. The deposited drug amount in the skin beneath the stratum corneum from MXS-LPSs, MX tincture and MXS solution accounted for about 59.80 ± 26.27 %, 43.18 ± 6.58 % and 32.55 ± 1.61 % of that in the whole skin, respectively. It is remarkable that MXS-LPSs showed a considerably increased accumulation in hair follicles when compared to MXS solution. The results of pharmacodynamic tests demonstrated that, compared to MX tincture, MXS-LPSs could more effectively stimulate hair regrowth and avoided the adverse effects. Importantly, the MXS-LPSs also reduced skin irritation and sensitization. Consequently, MXS-LPSs hold substantial promise in the treatment of AGA.
研究领域:
药剂学
·
皮肤科
·
纳米技术
·
药物递送系统
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2021
·
IF 15.881
Anran Yuan,Fan Xia,Qiong Bian,Haibin Wu,Yueting Gu,Tao Wang,Ruxuan Wang,Lingling Huang,Qiaoling Huang,Yuefeng Rao,Daishun Ling,Fangyuan Li,Jianqing Gao
Androgenetic alopecia (AGA) is highly prevalent in current society but lacks effective treatments. The dysregulation of the hair follicle niche induced by excessive reactive oxygen species (ROS) and insufficient vascularization in the perifollicular microenvironment is the leading cause of AGA. Herein, we designed a ceria nanozyme (CeNZ)-integrated microneedles patch (Ce-MNs) that can alleviate oxidative stress and promote angiogenesis simultaneously to reshape the perifollicular microenvironment for AGA treatment. On the basis of the excellent mechanical strength of Ce-MNs, the encapsulated CeNZs with catalase- and superoxide-mimic activities can be efficiently delivered into skin to scavenge excessive ROS. Moreover, the mechanical stimulation induced by the administration of MNs can remodel the microvasculature in the balding region. Compared with minoxidil, a widely used clinical drug for AGA treatment, Ce-MNs exhibited accelerated hair regeneration in the AGA mouse model at a lower administration frequency without inducing significant skin damage. Consequently, such a safe and perifollicular microenvironment-shaping MNs patch shows great potential for clinical AGA treatment.
研究领域:
纳米技术
·
皮肤科
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Qian Luo,Jiao Zhang,Samira Batur,Chuansheng Fu,Wei Chen,Qi Xie,Conglian Yang,Zhiping Zhang
Androgenic alopecia (AGA) is the most common type of hair loss, causing serious physical and mental distress to patients. The key factors contributing to AGA include oxidative stress and insufficient vascularization in the microenvironment around hair follicles. Currently, the available treatment options are limited, and there is no comprehensive treatment strategy with minimal side effects and optimal efficacy. Herein, we developed a novel minoxidil and epigallocatechin gallate co-loaded ionic liquids drug delivery system (ME@CGIL), which was simple to prepare and could effectively regulate hair follicle microenvironment homeostasis. After topical application, the ionic liquids, which had a certain function of promoting hair regrowth, facilitated drugs delivery into the epidermis and dermis while prolonging their retention time, so as to reduce the frequency and dosage requirements. ME@CGIL promoted hair regrowth by activating hair follicle stem cells, scavenging excessive reactive oxygen species and promoting neovascularization in the AGA mouse model, showing superior efficacy than commercially available minoxidil products. Altogether, this study may provide a simple and ingenious treatment strategy for AGA, which has great potential for clinical application.
研究领域:
药学
·
皮肤病学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）