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

Inflammation in hair follicles will reduce the effectiveness of minoxidil (MXD) in the treatment of androgen alopecia (AGA) caused by elevated androgen levels. To target multiple physiological and pathological processes in AGA, a novel natural bioactive compound modified transfersomes (MXD-Rg3@TFs) was prepared to replace cholesterol that may disrupt hair growth, with ginsenosides Rg3 (Rg3) that have anti-inflammatory effects on AGA. The effects of MXD, Rg3 and their combination on AGA were evaluated using dihydrotestosterone (DHT) induced human dermal papilla cells (DPCs), and the results showed that the combination of MXD and Rg3 can significantly promote the proliferation, reduce the level of intracellular ROS and inflammatory factors, and inhibit the aging of DHT induced DPCs. Compared with cholesterol membrane transfersomes (MXD-Ch@TFs), MXD-Rg3@TFs has similar deformability, smaller particle size and better stability. MXD-Rg3@TFs has also significant advantages in shortening telogen phase and prolonging the growth period of hair follicles in C57BL/6 mice than MXD-Ch@TFs and commercial MXD tincture. The prominent ability of MXD-Rg3@TFs to inhibit the conversion of testosterone to DHT and reduce the level of inflammatory factors suggested that Rg3 and MXD in MXD-Rg3@TFs have synergistic effect on AGA therapy. MXD-Ch@TFs with no irritation to C57BL/6 mice skin is expected to reduce the dose of MXD and shorten the treatment time, which would undoubtedly provide a promising therapeutic option for treatment of AGA.

Microneedle Delivery Platform Integrated with Codelivery Nanoliposomes for Effective and Safe Androgenetic Alopecia Treatment.

Although topical application of minoxidil is a widely used, FDA-approved therapy for androgenetic alopecia (AGA) treatment, it suffers from low bioavailability, the requirement for frequent long-term use, and side effects. With a similar structure as minoxidil, kopexil and kopyrrol are less toxic and have been commercialized, but show an inferior hair regeneration effect compared to minoxidil. Herein, we developed a hyaluronic acid (HA)-based dissolvable microneedles (MNs) delivery platform integrated with kopexil and kopyrrol coencapsulated nanoliposomes (KK-NLPs) to effectively and safely treat AGA. Facilitated by nanoliposomes and MNs, the encapsulated KK-NLPs performed efficient skin penetration and enhanced cellular internalization into human dermal papilla cells. Furthermore, within the target cells, the codelivered kopexil and kopyrrol show synergistic effects by orchestrating an upregulation in the expression of Ki67, ß-catenin, vascular endothelial growth factor (VEGF), and CD31. These molecular responses collectively foster cell proliferation, migration, and antioxidative effects, thereby facilitating the expedited progression of hair follicles (HFs) into the anagen phase and promoting peripheral angiogenesis. Notably, the KK-NLPs-integrated MNs treatment group exhibits noteworthy enhanced hair regeneration in vivo, with identical or superior therapeutic effects at a much lower dosage than that of minoxidil. These results suggest the great potential of this kopexil and kopyrrol codelivery nanoliposomes-integrated MNs platform for AGA treatment in a safe and efficient way.

Synergistic treatment of androgenetic alopecia with follicular co-delivery of minoxidil and cedrol in metal-organic frameworks stabilized by covalently cross-linked cyclodextrins.

Androgenetic alopecia seriously affects the physical and mental health of patients. The main clinical therapeutic agent, minoxidil tincture, is challenged by solvent irritation and dose-dependent side effects. Our recent work has identified a biosafety natural product, cedrol, that is synergistic in combination with minoxidil, thereby improving medication safety by substantially reducing the clinical dose of minoxidil. In addition, ccross-linked CD-MOF were designed as carriers for hair follicle delivery, and γ-CD in the carriers was cross-linked by diphenyl carbonate with covalent bonds to protect the CD-MOF from rapid disintegration in an aqueous environment. This improved nanocarrier has a drug loading of 25%, whereas nanocarriers increased drug delivery to the hair follicles through ratchet effect, and increased human dermal papilla cells uptake of drugs via endocytosis pathways mainly mediated by lattice proteins, energy-dependent active transport, and lipid raft-dependent, thus improved cell viability, proliferation, and migration, followed by significantly enhancing the anti-androgenetic alopecia effect, with cedrol focusing on inhibiting 5α-reductase and activating Shh/Gli pathway, and minoxidil, which up-regulated VEGF, down-regulated TGF-ß, and activated ERK/AKT pathway. This drug combination provides a new therapeutic strategy for androgenetic alopecia, while the newly developed cross-linked CD-MOF has been shown to serve as a promising follicular delivery vehicle.

Molybdenum nanoparticles as a potential topical medication for alopecia treatment through antioxidant pathways that differ from minoxidil.

BACKGROUND: Hair loss is a common dermatological condition including various types such as alopecia areata, androgenetic alopecia, etc. Minoxidil is a topical medication used for treating hair loss, which is effective for various types of alopecia. However, minoxidil has limitations in treating hair loss, such as slow onset of action and low efficacy, and it cannot effectively inhibit one of the major pathogenic factors of hair loss - excessive oxidative stress. METHODS: Transition metal elements with rapid electron transfer, such as molybdenum, have been extensively studied and applied for inhibiting oxidative stress. We established a mouse model for hair growth and intervened with nano-sized molybdenum, minoxidil, and a combination of both. The physicochemical properties of nano-sized molybdenum enabled it to mediate oxidative stress more quickly. RESULTS: The results showed that nano-sized molybdenum can accelerate hair growth, increase the number of local hair follicles, and reduce the expression of oxidative stress-related molecules such as iNOS, COX2, and androgen receptors. The combination of nano-sized molybdenum and minoxidil showed an additive effect in promoting hair growth. CONCLUSION: Our findings suggest that nano-sized molybdenum might be a potential topical medication for treating hair loss by inhibiting the oxidative stress pathway. Nano-sized molybdenum, alone or in combination with minoxidil, could be a promising therapeutic approach for patients with hair loss, particularly those who do not respond well to current treatments. Further clinical studies are warranted to confirm the efficacy and safety of this novel treatment.

Chitosan and its amphiphilic derivative nanoparticles loaded with Minoxidil for induction of hair growth: In vitro and in vivo evaluation.

Minoxidil is widely used for treating Androgenic Alopecia, but its low hydrophilicity promotes the use of co-solvents in commercial formulations, which could then cause skin irritations. Nano-drug delivery systems have been developed to improve the solubility of lipophilic molecules and increase the concentration of drugs in hair follicles, thereby minimizing side effects. Chitosan (CS) and Methylated Aminobenzyl Carboxymethyl Chitosan (MCS) nanoparticles containing Minoxidil were prepared and evaluated for their physicochemical properties, drug release profile, skin permeation, cytotoxicity, and animal hair growth. The results showed that MCS nanoparticles had a 60 % drug release compared to CS nanoparticles, with almost complete release in 2 h. MCS nanoparticles also showed a 20 % drug permeation from skin compared to 70 % for CS nanoparticles in 24 h. In 48 and 72 h, CS and MCS nanoparticles didn't exhibit any significant cytotoxicity. Animal study revealed a significant increase in hair growth from MCS nanoparticles compared to the commercial formulation in fourteen days. However, MCS nanoparticles were less efficient compared to CS nanoparticles. The use of MCS in nano-drug delivery systems is expected to continue to gain importance due to its ability to enhance the solubility of hydrophobic drugs, particularly in the treatment of skin diseases.

Methodological challenges in using human umbilical artery as a model for in vitro studies.

NEW FINDINGS: What is the central question of this study? What are the biggest challenges in performing in vitro studies on isolated human umbilical arteries? What is the main finding and its importance? The protocols presented in this study indicate some potential outcomes important for interpretation of the vascular responsivities of human umbilical arteries and could be useful for planning future in vitro studies with human umbilical arteries. ABSTRACT: Human umbilical artery (HUA) preparations are of particular importance for in vitro studies on isolated blood vessels because their sampling is not risky for the patient, and they can provide the closest possible impression of changes related to the uteroplacental circulation during pre-eclampsia. Using organ bath techniques, useful experimental protocols are provided for measuring some pathophysiological phenomena in the vascular responses of HUAs. Several vasoconstrictors (serotonin, prostaglandin F and phenylephrine) and vasodilators (acetylcholine and minoxidil) were seleted for determination of their vasoactivity in HUAs. The role of L-type voltage-operated calcium channels and different types of potassium channels (KATP , BKCa and KV ) were assessed, as was the impact of homocysteine. Serotonin was confirmed to be the most potent vasoconstrictor, while acetylcholine and phenylephrine caused variability in the relaxation and contraction response of HUA, respectively. The observed increase in serotonin-induced contraction and a decrease in minoxidil-induced relaxation in the presence of homocysteine suggested its procontractile effect on HUA preparations. Using selective blockers, it was determined that KATP and KV channels participate in the minoxidil-induced relaxation, while L-type voltage-dependent Ca2+  channels play an important role in the serotonin-induced contraction. The presented protocols reveal some of the methodological challenges related to HUA preparations and indicate potential outcomes in interpreting the vascular effects of the investigated substances, both in physiological conditions and in the homocysteine-induced pre-eclampsia model.

Co-delivery of minoxidil and tocopherol acetate ethosomes to reshape the hair Follicular Microenvironment and promote hair regeneration in androgenetic alopecia.

The most prevalent kind of hair loss is androgenic alopecia (AGA), which is characterized by hair follicle miniaturization and microenvironment dysfunction. Although topical Minoxidil (MXD) was considered to be a safe and effective treatment for AGA, excess reactive oxygen species (ROS) and lower sulfotransferase activity in the hair follicular microenvironment led to an unsatisfactory treatment of AGA. Here, we developed the ethosome (MTE) load of minoxidil and tocopherol acetate to improve the therapeutic effect of MXD on androgenic alopecia. It could regulate the microenvironment around hair follicles, promote the telogen-to-anagen transition of hair follicles, and boost hair regeneration, thus achieving a synergistic effect of 1 + 1 > 2. The results proved that MTE showed excellent stability, biosafety, and good dermal and follicular permeability in vitro. The hair regeneration ability of AGA model mice showed that the co-delivery ethosome might regulate the microenvironment around the hair follicles and improve hair regeneration in comparison to the commercial minoxidil tincture alone. As a result, the strategy provided a promising new strategy for the treatment of AGA.

Modulation of hair growth by topical drug delivery enhanced by STAR particles.

Topical treatments to modulate hair growth are generally limited by low drug bioavailability due to poor skin permeability. Here, we studied the use of STAR particles, which are millimeter-sized ceramic particles with protruding microneedles, to form micropores in the skin to increase skin permeability to hair growth-modulating drugs. STAR particle design and fabrication were optimized, and the resulting STAR particles were shown to reduce lag time and increase skin permeability to minoxidil and acyclovir by more than three-fold compared to no treatment in pig skin ex vivo. In rats, STAR particles also improved topical delivery of minoxidil and acyclovir, which resulted in an increase or a decrease in the number, length and/or thickness of hairs and/or the number of anagen-phase hair follicles after minoxidil or acyclovir treatment, respectively. Clinical exam and histological evaluation showed no evidence of skin irritation or other adverse effects of the treatments. We conclude that STAR particles can increase topical delivery of minoxidil and acyclovir to improve modulation of hair growth promotion and inhibition, respectively.

New Target for Minoxidil in the Treatment of Androgenetic Alopecia.

Objective: To investigate the mechanism of minoxidil in treating androgenetic alopecia (AGA). Methods: The mechanism of action of minoxidil on AGA was first systematically investigated from the viewpoint of network pharmacology, including minoxidil-AGA target prediction, protein-protein interaction (PPI) network analysis, molecular docking and enrichment analysis of targets related to minoxidil and AGA, and dermal papilla cell assays to confirm the viability of prediction. Results: The combined analysis revealed that minoxidil treatment of AGA not only acts on androgenic receptors (AR) but also on 2 new targets, steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1) and aromatase (CYP19A1). The biological processes linked to these targets were concentrated on several pathways, including enzymes and hormones. Further experiments have revealed that minoxidil suppresses the expression of AR and CYP17A1, boosts the activity of CYP19A1, decreases the formation and binding of dihydrotestosterone, and enhances the production of estradiol. Through these changes, minoxidil acts as a treatment for AGA. Conclusion: Minoxidil may act by altering hormonal and enzymatic pathways. Our study finds two new targets (CYP17A1, CYP19A1) of minoxidil and demonstrates that minoxidil inhibits AR. These targets may provide new ideas for drug research.

Combination of adipose-derived stem cell conditioned media and minoxidil for hair regrowth in male androgenetic alopecia: a randomized, double-blind clinical trial.

INTRODUCTION: Treatments for AGA have yet to produce satisfactory outcomes and may cause intolerable side effects. Recent studies have reported that adipose tissue-derived stem cell conditioned media (ADSC-CM) could induce hair growth and regeneration. OBJECTIVE: To investigate the efficacy of ADSC-CM combined with minoxidil for hair regeneration therapy in male AGA. METHODS: This study lasted for 6 weeks. Subjects were divided into two groups: concentrated and non-concentrated ADSC-CM. Scalp was divided vertically in half before intradermal injection was administered from the frontal region of the scalp toward the vertex with a 30G needle, spaced about 1 cm apart. Treatment side received 2 ml of ADSC-CM; the other side was given 2 ml of NaCl 0.9% as placebo. Patients applied 5% minoxidil twice daily post-injection. Improvements were assessed using photographs and trichoscan every 2 weeks. RESULTS: Hair count, hair density, and mean thickness increased significantly on both sides after 6 weeks, while vellus rate decreased proportionally with the increase of terminal rate. No statistically significant differences between treatment groups were found. Minimum side effects were reported, and subjects were satisfied with the results. CONCLUSION: Combination of ADSC-CM and minoxidil could be a potential agent for hair regrowth. Follow-up research with extensive populations, longer duration, and different study design may be required to confirm the exact mechanisms of ADSC-CM on hair growth. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05296863. Registered 25 March 2022-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05296863 .

Sensitive Quantitative In Vivo Assay for Evaluating the Effects of Biomolecules on Hair Growth and Coloring Using Direct Microinjections into Mouse Whisker Follicles.

Many people suffer from hair loss and abnormal skin pigmentation, highlighting the need for simple assays to support drug discovery research. Current assays have various limitations, such as being in vitro only, not sensitive enough, or unquantifiable. We took advantage of the bilateral symmetry and large size of mouse whisker follicles to develop a novel in vivo assay called "whisker follicle microinjection assay". In this assay, we plucked mouse whiskers and then injected molecules directly into one side of the whisker follicles using microneedles that were a similar size to the whiskers, and we injected solvent on the other side as a control. Once the whiskers grew out again, we quantitatively measured their length and color intensity to evaluate the effects of the molecules on hair growth and coloring. Several chemicals and proteins were used to test this assay. The chemicals minoxidil and ruxolitinib, as well as the protein RSPO1, promoted hair growth. The effect of the clinical drug minoxidil could be detected at a concentration as low as 0.001%. The chemical deoxyarbutin inhibited melanin production. The protein Nbl1 was identified as a novel hair-growth inhibitor. In conclusion, we successfully established a sensitive and quantitative in vivo assay to evaluate the effects of chemicals and proteins on hair growth and coloring and identified a novel regulator by using this assay. This whisker follicle microinjection assay will be useful when investigating protein functions and when developing drugs to treat hair loss and abnormal skin pigmentation.

Fabrication of carboxymethyl cellulose/hyaluronic acid/polyvinylpyrrolidone composite pastes incorporation of minoxidil-loaded ferulic acid-derived lignin nanoparticles and valproic acid for treatment of androgenetic alopecia.

Androgenetic alopecia (AGA) is a transracial and cross-gender disease worldwide with a higher prevalence among young individuals. Traditional oral or subcutaneous injections are often used to treat AGA, however, they may cause severe side-effects and therefore effective treatments for AGA are currently lacking. In this work, to treat AGA, we developed a composite paste system based on minoxidil (MXD)-loaded nanoparticles and valproic acid (VPA) with the assistance of roller-microneedles (roller-MNs). The matrix of composite paste systems is carboxymethyl cellulose (CMC), hyaluronic acid (HA) and polyvinylpyrrolidone (PVP). The roller-MNs can create microchannels in the skin to enhance drug transdermal efficiency. With the combined effects of the stimulation hair follicle (HF) regrowth by upregulating Wnt/beta-catenin of VPA and the mechanical microchannels induced by roller-MNs, the as-prepared composite paste systems successfully boost perifollicular vascularization, and activate hair follicle stem cells, thereby inducing notably faster hair regeneration at a lower administration frequency on AGA mouse model compared with minoxidil. This approach offers several benefits, including the avoidance of efficacy loss due to the liver's first-pass effect associated with oral drug, reduction in the risk of infection from subcutaneous injection, and significant decrease in the side effects of lower-dose MXD.

Natural Compounds Used for Treating Hair Loss.

Hair loss or alopecia is a common dermatological condition affecting up to 2% of the world population. It is often caused by hereditary factors, such as male or female pattern baldness, but it can also result from various environmental factors, an unbalanced diet, or chronic illness. While hair loss is not life-threatening, it can cause significant anxiety, depression, and other psychological problems, ultimately impacting an individual's quality of life. Various treatments for hair loss, including both synthetic drugs, such as minoxidil and finasteride, or medicinal herbs, have been approved by the Food and Drug Administration. Despite synthetic drugs' effectiveness, they may come with potential side effects. Natural remedies have been proposed as a viable option for treating hair loss because many chronic disorders can cause alopecia. As such, this review focuses on identifying alternative, efficient treatment agents with limited side effects. Specifically, it looks into medicinal plants as potential healing agents for treating hair loss. To gather relevant information for the study, multiple databases were searched, including Scopus, PubMed, and Google Scholar. A comprehensive search was conducted using a range of search terms, such as "hair loss", "alopecia", "natural remedies for hair loss", "herbal treatments for hair loss", and others to extract relevant scientific articles. Many medicinal plants and natural compounds have shown potential in reducing hair loss, thanks to their anti-inflammatory and antioxidant properties and the ability to improve local metabolism when applied externally. According to existing literature, herbal extracts and formulations derived from plants, such as Urtica dioica, Humulus lupulus, Serenoa repens, Vitis vinifera, Pygeum africanum, Cucurbita pepo, etc., as well as certain individual herbal compounds, micronutrients, bee products, and keratin, may be effective in reducing hair loss directly or indirectly. Research suggests that medicinal plants and a variety of natural compounds hold promise in promoting hair growth and preventing alopecia.

The medicinal activity of lyophilized aqueous seed extract of Lepidium sativum L. in an androgenic alopecia model.

This study evaluated the topical effect of Lepidium sativum lyophilized seed extract (LSLE) towards Sustanon-induced alopecia in male adult Wistar albino rats in vivo, compared to minoxidil topical reference standard drug (MRD). LC-MS/MS together with molecular networking was used to profile the metabolites of LSLE. LSLE treated group revealed significant changes in alopecia related biomarkers, perturbation of androgenic markers; decline in testosterone level and elevation in 5α-reductase (5-AR); decline in the cholesterol level. On the other hand, LSLE treated group showed improvement in vascular markers; CTGF, FGF and VEGF. Groups treated topically with minoxidil and LSLE showed significant improvement in hair length. LC-MS/MS profile of LSLE tentatively identified 17 constituents: mainly glucosinolates, flavonoid glycosides, alkaloids and phenolic acids. The results point to the potential role of LSLE in the treatment of alopecia through decreasing 5(alpha)-dihydrotestosterone levels. Molecular docking was attempted to evaluate the probable binding mode of identified compounds to androgen receptor (PDB code: 4K7A).

In Vivo Study of the Effects of Propranolol, Timolol, and Minoxidil on Burn Wound Healing in Wistar Rats.

Propranolol, timolol, and minoxidil have all shown benefits in treatment of burn injury and other skin wounds. The study evaluated their effects on full-thickness thermal skin burns in a Wistar rat model. Performed on 50 female rats; two dorsal skin burns were created on each animal. On the next day, the rats were divided into 5 groups (n = 10); each has received a specific treatment daily for 14 days: group I-topical vehicle (control), group II-topical silver sulfadiazine (SSD), group III-oral propranolol (5.5 mg) associated with topical vehicle, group IV-topical timolol 1% cream, and group V-topical minoxidil 5% cream. Wound contraction rates, malondialdehyde (MDA), glutathione (GSH, GSSG), and catalase activity in skin and/or serum were evaluated, and histopathological analyses were performed. Propranolol did not show advantages in necrosis prevention and wound contraction and healing, and did not reduce oxidative stress. It impaired keratinocyte migration, and promoted ulceration, chronic inflammation, and fibrosis, yet reducing the necrotic zone. Timolol prevented necrosis and promoted contraction and healing, increased antioxidant capacity and promoted keratinocyte migration and neo capillarization in comparison to the other treatments. Minoxidil reduced necrosis and enhanced contraction, resulting in positive outcomes after 1 week of treatment regarding local antioxidant defense, keratinocyte migration, neo capillarization, chronic inflammation, and fibrosis rates. However, after 2 weeks, it resulted in contrasting outcomes. In conclusion, topical timolol promoted wound contraction and healing, reducing local oxidative stress and improving keratinocyte migration, bringing arguments for potential benefits in skin epithelization.

Boosting hair growth through follicular delivery of Melatonin through lecithin-enhanced Pickering emulsion stabilized by chitosan-dextran nanoparticles in testosterone induced androgenic alopecia rat model.

The strategy in this work was loading Melatonin (MEL), the powerful antioxidant photosensitive molecule, in novel Pickering emulsions (PEs) stabilized by chitosan-dextran sulphate nanoparticles (CS-DS NPs) and enhanced by lecithin, for treatment of androgenic alopecia (AGA). Biodegradable CS-DS NPs dispersion was prepared by polyelectrolyte complexation and optimized for PEs stabilization. PEs were characterized for droplet size, zeta potential, morphology, photostability and antioxidant activity. Ex-vivo permeation study through rat full thickness skin was conducted with optimized formula. Differential tape stripping trailed by cyanoacrylate skin surface biopsy was executed, for quantifying MEL in skin compartments and hair follicles. In-vivo evaluation of MEL PE hair growth activity was performed on testosterone induced AGA rat model. Visual inspection followed by anagen to telogen phase ratio (A/T) and histopathological examinations were conducted and compared with marketed 5% minoxidil spray "Rogaine ®". Data showed that PE improved MEL antioxidant activity and photostability. Ex-vivo results displayed MEL PE high follicular deposition. In-vivo study demonstrated that MEL PE treated testosterone induced AGA rat group, restored hair loss and produced maximum hair regeneration along with prolonged anagen phase amongst tested groups. The histopathological examination revealed that MEL PE prolonged anagen stage, increased follicular density and A/T ratio by 1.5-fold. The results suggested that lecithin-enhanced PE stabilized by CS-DS NPs was found to be an effective approach to enhance photostability, antioxidant activity and follicular delivery of MEL. Thus, MEL-loaded PE could be a promising competitor to commercially marketed Minoxidil for treatment of AGA.

Dissolving Microneedle Patch Integrated with Microspheres for Long-Acting Hair Regrowth Therapy.

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.

Advances in microneedles research based on promoting hair regrowth.

Alopecia is the most common and difficult-to-treat hair disorder. It usually brings a significant psychological burden to the patients. With the growing popularity of alopecia, the study of alopecia has gained more attention. Currently, only minoxidil and finasteride have been approved by the FDA for the treatment of alopecia, but the efficacy has always been unsatisfactory. As a new form of transdermal drug delivery, microneedles have been widely used in the treatment of alopecia and have proven to be effective. Microneedles delivery can improve the efficiency of local drug delivery and patients' compliance, which can achieve better therapeutic effects on hair-related diseases. Therefore, microneedles have gained much attention in the field of alopecia and hair regrowth promotion in recent years. This review summarizes the last decade of research on the microneedles delivery design for the treatment of alopecia or promotion of hair regrowth and provides a comprehensive evaluation of this field.

Effect of topical naringenin and its combination with minoxidil on enhancing hair growth in a mouse model.

This study aimed to investigate the efficacy of naringenin (NAR) in reducing hair loss. Twenty-four adult Wistar Albino mice, weighing between 25-35 g and aged 6-7 weeks, were used in this research. The dorsal hair of these mice was meticulously clipped and stained subsequently. The mice were randomly divided into four groups (n=6 for each group): (1) negative control group, treated with absolute ethanol alcohol as the vehicle (2) minoxidil (5%) treated group; (3) 0.5% naringenin treated group, and (4) naringenin plus minoxidil treated group. The treatment groups had significantly higher total antioxidant capacity in tissue levels and increased serum levels of vascular endothelial growth factor compared to the control group. No significant differences were observed in keratinocyte growth factor tissue levels between the treatment and control groups. However, the medication significantly increased hair growth, hair follicle diameter expansion, and hair follicle quantity compared to the control group. The finding suggests that the antioxidant and anti-inflammatory properties of NAR significantly reduced hair loss in adult male mice.

[Effects of Skin Environmental Changes by Steam Towel, Ethanol, l-Menthol and Carpronium on the Drug Behavior in the Minoxidil Nanoparticles-applied Mice].

We previously designed the formulation containing minoxidil (MXD) nanoparticles (MXD-NPs), and found that the MXD-NPs can mainly deliver MXD into hair bulbs via hair follicles pathway, and that the therapeutic efficiency for hair growth is higher in comparison with the formulation containing dissolved MXD. In this study, we investigated whether the skin environmental changes by the treatment of steam towel, ethanol, l-menthol and commercially available (CA) carpronium affect the drug behavior in the MXD-NPs-applied mice. The steam towel, ethanol, l-menthol and CA-carpronium were pre-treated 3 min before MXD-NPs application, and the MXD content in the hair bulge, bulb, skin tissue and blood of mice were measured 4 h after MXD-NPs application. No significant difference of MXD levels in the blood was observed by the pre-treatment of steam towel, ethanol, l-menthol and CA-carpronium. On the other hand, the pre-treatment of steam towel and l-menthol enhanced the MXD levels in hair bulge and/or bulb. Although, the MXD levels in hair bulge and bulb were not changed by the pre-treatment of ethanol, the MXD levels in skin tissue was higher than that of saline-pre-treated group (control). The MXD levels in hair bulge, bulb and skin tissue of mice pre-treated with CA-carpronium were remarkably higher in comparison with control. In conclusion, we showed that the changes in skin environment by the steam towel, ethanol, l-menthol and CA-carpronium affected the absorption of MXD-NPs, and these increased MXD levels in the hair bulb and blood by the combination may enhance the therapeutic efficiency without side effects.