Relevance of topical application of minoxidil laden nano-lipid for hair growth enhancement

Targeting sonic hedgehog (shh) signaling pathways by the concentration-dependent topical resveratrol for protection from cyclophosphamide-induced alopecia in a mouse model.

Existing therapies for androgenetic alopecia (AGA) fall short of expectations due to the complex pathogenesis, deficient drug enrichment, and obvious adverse effects. Although elevated dihydrotestosterone (DHT) is responsible for the miniaturization of hair follicles (HFs), cell aging has been found to be closely associated with AGA, however not received sufficient attention before. In this study, we first explored the deleterious effects of DHT on HFs, then identified the anti-aging potential of conjugated linoleic acid (CLA) from several polyunsaturated fatty acids. We then developed CLA-loaded nanovesicles (Arg-CLAVs) capable of counteracting DHT-induced HF aging. Arg-CLAVs rejuvenated DHT-induced senescent cells by alleviating oxidative stress, reducing the production of senescence-associated secretory phenotype, and modulating the MAPK-ERK signaling pathway. Moreover, Arg-CLAVs enhanced the HF niche by facilitating angiogenesis, preserving local oxidative homeostasis, and promoting the proliferation and migration of dermal papilla cells. Given its unique properties of nanocarriers, Arg-CLAVs exhibited better skin retention and HF targeting ability compared to the normal tincture. Subsequently, minoxidil (MNX) was loaded into the nanovesicle (MNX@Arg-CLAVs) and evaluated for its hair growth-promoting efficacy in vivo. Our results demonstrated that, in both male and female AGA mice, MNX@Arg-CLAVs with reduced MNX dosage and lower organic solvent contents, exhibited stronger effects on hair regeneration promotion and anti-aging in HFs, while inducing less formulation-associated skin irritation than commercial topical MNX tincture. In sum, this study developed a novel nanoplatform with HF anti-aging activity for AGA that enables synergistic effects with existing drugs.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1186/s12951-025-03865-2.

Androgenetic alopecia (AGA) is a prevalent form of non-scarring hair loss. Standard treatments, which include minoxidil (MXD) tincture and foam, face challenges due to MXD's water insolubility and poor skin permeability. The result is extended treatment duration and reduced therapeutic effectiveness. This study utilized stevioside (STV), a natural sweetener derived from the Stevia plant, as a novel solubilizing excipient and microneedle (MN) material. A solid dispersion of STV with insoluble drugs is developed and molded into an MN patch. STV significantly increased MXD's solubility to 47mgmL-1 in water, ≈18 fold higher than the control. STV solubilizes MXD by forming micelles in aqueous solution with a critical micelle concentration of 15mgmL-1. In vitro skin permeation studies showed cumulative drug release of 85% and 18% skin retention for the MN patch, which indicated excellent drug absorption into the skin. Animal studies demonstrated that the MN patch significantly promoted hair growth. There is a significant increase in hair follicle transition to the growth phase, which resulted in 67.5% coverage of the treatment area by day 35. Collectively, the results highlight the potential of the STV MN delivery system for the treatment of AGA.

Objective: This research aimed to formulate a minoxidil (MXD) nanoemulgel to optimize follicular delivery, reduce side effects, and improve patient compliance in treating androgenetic alopecia. Methods: A nanoemulgel was developed using the spontaneous emulsification technique, with oleic acid as the base, propylene glycol as the co-surfactant, and Tween 20 as the surfactant. MXD was loaded into the formulation to enhance medication solubilization and skin penetration. Results: The formulated nanoemulgels exhibited a negative zeta potential of (−27 ± 1) and a high entrapment efficiency of (96.2 ± 4.02%). In vitro testing demonstrated sustained release of MXD from the nanoemulsion (NE). Conclusion: The developed MXD nanoemulgel shows promise in enhancing the activity of MXD for the treatment of androgenetic alopecia. The negative zeta potential, high entrapment efficiency, and sustained release profile suggest potential improvements in follicular delivery and therapeutic efficacy. This formulation could offer a more effective and patient-friendly alternative for managing androgenetic alopecia, addressing the limitations associated with conventional MXD formulations.

Commercial Minoxidil (MXD) is commonly used as a vasodilator agent of hair follicles for providing direct dermal papilla cell proliferation and consequently enhancing the rate of hair growth. The current study attempted to improve the bioactivity and water solubility of MXD by producing nanocrystal structures and investigating the obtained hair growthstimulating activity on C57BL/6 mice. The MXD nanoparticles (MXD-NPs) were prepared through a bead mill and ultrasonic process and characterized by DLS, XRD, UV-Vis, FTIR, FESEM, TEM, and Zeta-potential techniques. The cytotoxicity of MXD-NPs was studied on human dermal fibroblast (HDF) by MTT assay. Lastly, we analyzed the comparative hair growth inductive activity of certain MXD-NPs concentrations on C57BL/6 mice. The stabled MXD-NPs (-46 mV, 21.9 nm) caused a significant increase in the hair growth rate of C57BL/6 mice by running a safe site-specific delivery mechanism on the targeted pilosebaceous follicles when compared to MXD. The MXD-NPs-receiving mice exhibited a greater rate of anagen/telogen follicular when compared with MXD-treated types, which verified the improvement of their hair re-growing and follicular-stimulative activities. Therefore, these outcomes confirmed the potential of MXD-NPs for substituting its commercial solution format as a safe and efficient iso-formulation structure.

Androgenetic Alopecia (AGA), the most common form of patterned hair loss, is genetically inherited, potentially treatable scalp hair loss that occurs only in the frontal and central scalp of predisposed individuals. The 5-Alpha Reductase (5-AR) enzyme converts testosterone into Dihydrotestosterone (DHT) under hormonal influences, which results in hair follicle miniaturization and the development of AGA. Finasteride (FIN) and Minoxidil (MXD) are the only two U. S. Food and Drug Administration (FDA)-approved drugs available; however, their drawbacks, such as topical and systemic side effects and inconsistent effectiveness, have prompted research into more sophisticated drug delivery methods. Nanocarriers show potential for targeted drug administration in the treatment of AGA, including liposomes, niosomes, Solid Lipid Nanoparticles (SLNs), polymeric nanoparticles, transferosomes, and Nanostructured Lipid Carriers (NLCs). These nanocarriers enhance drug stability, target follicular delivery, and maintain drug release by overcoming the stratum corneum barrier. Nanocarriers reduce systemic exposure while increasing drug bioavailability and concentration at target sites. For example, antioxidant-based formulations lessen oxidative stress, and nanoparticles loaded with spironolactone block androgen receptors and inhibit 5-AR activity within hair follicles. Nanotechnology enhances treatments and enables the use of new therapeutic agents, including anti-inflammatory and regenerative organic substances. Preclinical results are encouraging, but limited robust trials, regulatory obstacles, and financial limitations impede the translation to clinical practice. This review highlights nanotechnology’s potential to revolutionize AGA treatment through localized, patient-centric strategies, emphasizing the need for clinical validation and scalable manufacturing.

Liposomes enhance the hair follicle delivery of minoxidil sulfate with improved treatment of androgenic alopecia.

Co-delivery of minoxidil and finasteride via ionic liquid and cyclodextrin-assisted in situ thermosensitive hydrogel for synergistic treatment of androgenic alopecia.

Purpose:Anal fissure (AF) is a common anorectal condition causing pain, bleeding, and other perianal discomfort. This study conducts a network meta-analysis (NMA) to compare the efficacy and side effect profiles of pharmacological treatments for AF, including diltiazem (DTZ), glyceryl trinitrate (GTN), nifedipine (ND), minoxidil (MD), and lidocaine (LC).Methods:Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a systematic review and NMA were performed. Randomized controlled trials (RCTs) comparing non-surgical treatments for AF were sourced from PubMed, Cochrane Library, Embase, and Medline. The primary outcome was AF healing, with secondary outcomes including recurrence rates, pain reduction (visual analog scale), and adverse effects. Statistical analysis utilized odds ratios and surface under the cumulative ranking values for treatment ranking.Results:Twenty-two RCTs involving a total of 1770 participants were included in the analysis. ND demonstrated the highest healing rate, followed by DTZ and MD. LC exhibited the lowest healing rate. DTZ had the lowest recurrence rate and was the most effective in pain reduction, whereas LC had the highest recurrence rate and was the least effective in alleviating pain. The incidence of adverse effects with MD was relatively low, second only to LC, while GTN had the highest rate of adverse effects.Conclusion:ND had the highest healing rate and should be considered as a first-line non-surgical treatment for AFs. Given the elevated incidence of adverse reactions associated with nitroglycerin, its use should be avoided in order to minimize the risk of significant toxicities and side effects. Additionally, because of its outstanding analgesic properties, DTZ is recommended as the preferred option for patients with heightened sensitivity to pain, but more studies are needed to evaluate its efficacy.

Hair loss affects significant social and psychological well-being issues of the person. Thus, various drugs, ingredients, and technologies are being developed to overcome it. Minoxidil (MXD) is a representative hair loss treatment drug because it suppresses the production of dihydrotestosterone and induces vasodilation. However, since MXD has various side effects when used orally, it is more desirable to use it topically. In this work, we disclosed a new polymeric formulation (MXD@CP) based on citric acid (CA) dimethylsiloxane polymer (CP) for the effective transdermal delivery of MXD. The polymer that induced ring-opening polymerization based on CA was named CA-siloxane polymer (CP). After CP synthesis, MXD was loaded onto CP to form MXD@CP. The formed MXD@CP was confirmed to have efficacy as a transdermal delivery system through various material property analyses and biotoxicity and therapeutic efficacy analyses. In these results, CP stably loaded MXD up to 5%, a concentration used in clinical practice, and showed higher hair growth efficacy and hair follicle formation efficacy compared to MXD@PBS. In the animal study, MXD@CP showed a superior hair growth effect which suggests its potential as a next-generation hair loss treatment agent. The online version contains supplementary material available at 10.1007/s13534-025-00460-0.

Androgenetic alopecia (AGA)-a condition characterized by hair loss due to aging, autoimmune responses, stress, and other factors-results in hair follicle (HF) shrinkage and dermal papilla cell apoptosis. So far, only minoxidil (MXD) and finasteride have been approved for AGA treatment. However, both drugs have serious side effects, including hypersensitivity and sexual dysfunction. Hence, novel treatment agents are required for AGA. Although metformin (Met) is primarily a diabetes drug, it is also known to promote hair growth. However, it shows low transdermal permeability, and the mechanisms underlying its therapeutic effects on AGA remain unclear. Two-dimensional black phosphorus nanosheets (BP NSs) have attracted attention as drug carriers due to their low cytotoxicity, good biocompatibility, and strong antioxidant capacity. However, they are unstable, prone to degradation, and unsuitable for transdermal drug delivery. Fortunately, this limitation can be addressed through modification strategies, such as polyethylene glycol (PEG) addition (PEGylation). Here, we PEGylated BP NSs to improve their stability and loaded them with Met to generate a transdermal system (BP-PEG-Met) for AGA treatment. Compared with topical MXD, BP-PEG-Met markedly promoted hair regeneration while inducing fewer side effects. BP-PEG-Met scavenged excessive reactive oxygen species in skin cells, reducing the oxidative stress around HFs. Moreover, it up-regulated the expression of vascular endothelial growth factor (VEGF) and platelet-endothelial cell adhesion molecule-1 (CD31) in dermal papillae, inducing angiogenesis around HFs and accelerating the hair cycle toward anagen. Overall, this BP-PEG-Met transdermal delivery system showed marked clinical potential as a multifunctional tool for treating alopecia and possibly managing other skin conditions.

In this study, we attempted to enhance the delivery of minoxidil (MXD) nanocrystals into hair follicles for efficacious hair growth treatment. We applied a bead milling method and designed an MXD nanocrystal dispersion containing methylcellulose (MC) and gum arabic (GA), termed MG-MXD@NP, with a particle size of 110 nm. In vivo studies in C57BL/6 mice showed that MG-MXD@NP improved MXD delivery to the skin tissue, hair bulges, and hair bulbs, resulting in earlier and superior hair growth compared with a commercially available MXD lotion (Riup 5%, CA-MXD). These findings were consistent with the increased MXD contents observed in the hair bulge and hair bulb regions in the MG-MXD@NP-treated mice, and suggested a correlation between the efficiency of MXD delivery and efficacy of promotion of hair growth by products containing MXD. Furthermore, delivery of MXD using MG-MXD@NP was associated with elevated expression levels of CD34 and CD200, markers of hair follicle epithelial stem cells, which are crucial for promoting hair growth. Thus, it is possible that the upregulation of CD34 and CD200 in the MG-MXD@NP-treated mice reflects activation of the papilla cells and hair follicle stem cells known to be closely associated with hair growth enhancement. In conclusion, MG-MXD@NP, containing MXD nanocrystals in combination with MC and GA, exhibited a superior hair growth effect as compared with conventional MXD formulations. These findings suggest that this novel delivery method for MXD could represent a promising treatment approach for hair loss.

Voltammetric detection with a comprehensive electrochemistry study of minoxidil using nuclear magnetic resonance and infrared analyses: Applications in the forensic and pharmaceutical fields

Minoxidil cyclodextrin complexes and their inclusion in transfersomes for the enhancement of therapeutic effect on androgenic alopecia

Cellulose nanocrystal-stabilized Pickering emulsion gels as vehicles for follicular delivery of minoxidil

Aging (senescence) is an unavoidable biological process that results in visible manifestations in all cutaneous tissues, including scalp skin and hair follicles. Previously, we evaluated the molecular function of adenosine in promoting alopecia treatment in vitro. To elucidate the differences in the molecular mechanisms between minoxidil (MNX) and adenosine, gene expression changes in dermal papilla cells were examined. The androgen receptor (AR) pathway was identified as a candidate target of adenosine for hair growth, and the anti-androgenic activity of adenosine was examined in vitro. In addition, ex vivo examination of human hair follicle organ cultures revealed that adenosine potently elongated the anagen stage. According to the severity of alopecia, the ratio of the two peaks (terminal hair area/vellus hair area) decreased continuously. We further investigated the adenosine hair growth promoting effect in vivo to examine the hair thickness growth effects of topical 5% MNX and the adenosine complex (0.75% adenosine, 1% penthenol, and 2% niacinamide; APN) in vivo. After 4 months of administration, both the MNX and APN group showed significant increases in hair density (MNX + 5.01% (p < 0.01), APN + 6.20% (p < 0.001)) and thickness (MNX + 5.14% (p < 0.001), APN + 10.32% (p < 0.001)). The inhibition of AR signaling via adenosine could have contributed to hair thickness growth. We suggest that the anti-androgenic effect of adenosine, along with the evaluation of hair thickness distribution, could help us to understand hair physiology and to investigate new approaches for drug development.

Alopecia areata (AA) is a chronic autoimmune disease characterized by bald patches in certain areas of the body, especially the scalp. Minoxidil (MNX), as a first-line treatment of AA, effectively induces hair growth. However, oral and topical administration pose problems, including low bioavailability, risk of uncontrolled hair growth, and local side effects such as burning hair loss, and scalp irritation. In the latest research, MNX was delivered to the skin via microneedle (MN) transdermally. The MNX concentration was distributed throughout the needle so that drug penetration was reduced and had the potential to irritate. In this study, we formulated MNX into three-layer dissolving microneedles (TDMN) to increase drug penetration and avoid irritation. Physicochemical evaluation, parafilm, was used to evaluate the mechanical strength of TDMN and showed that TDMN could penetrate the stratum corneum. The ex-vivo permeation test showed that the highest average permeation result was obtained for TDMN2, namely 165.28 ± 31.87 ug/cm2, while for Minoxidil cream it was 46.03 ± 8.5 ug/cm2. The results of ex vivo and in vivo dermatokinetic tests showed that the amount of drug concentration remaining in the skin from the TDMN2 formula was higher compared to the cream preparation. The formula developed has no potential for irritation and toxicity based on the HET-CAM test and hemolysis test. TDMN is a promising alternative to administering MNX to overcome MNX problems and increase the effectiveness of AA therapy.

Synergistic therapeutic effect of ginsenoside Rg3 modified minoxidil transfersomes (MXD-Rg3@TFs) on androgenic alopecia in C57BL/6 mice

Minoxidil/salicylic acid hydrogel formulated for alopecia treatment: Supramolecular interactions modulate physicochemical properties and biological activities revealed by experimental and theoretical studies