RESUMO
The T-BOX transcription factor TBX1 is essential for the development of the pharyngeal apparatus and it is haploinsufficient in DiGeorge syndrome (DGS), a developmental anomaly associated with congenital heart disease and other abnormalities. The murine model recapitulates the heart phenotype and showed collagen accumulation. We first used a cellular model to study gene expression during cardiogenic differentiation of WT and Tbx1-/- mouse embryonic stem cells. Then we used a mouse model of DGS to test whether interfering with collagen accumulation using an inhibitor of lysyl hydroxylase would modify the cardiac phenotype of the mutant. We found that loss of Tbx1 in a precardiac differentiation model was associated with up regulation of a subset of ECM-related genes, including several collagen genes. In the in vivo model, early prenatal treatment with Minoxidil, a lysyl hydroxylase inhibitor, ameliorated the cardiac outflow tract septation phenotype in Tbx1 mutant fetuses, but it had no effect on septation in WT fetuses. We conclude that TBX1 suppresses a defined subset of ECM-related genes. This function is critical for OFT septation because the inhibition of collagen cross-linking in the mutant reduces significantly the penetrance of septation defects.
Assuntos
Síndrome de DiGeorge , Modelos Animais de Doenças , Minoxidil , Proteínas com Domínio T , Animais , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/metabolismo , Síndrome de DiGeorge/tratamento farmacológico , Síndrome de DiGeorge/patologia , Camundongos , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Minoxidil/farmacologia , Colágeno/metabolismo , Diferenciação Celular/efeitos dos fármacosRESUMO
BACKGROUND: Female pattern hair loss (FPHL) is the most prevalent type of alopecia among adult women. Presently, topical minoxidil stands as the sole treatment endorsed by the FDA. Addressing cases of FPHL in individuals who develop contact dermatitis in response to minoxidil can pose a challenge for dermatologists. OBJECTIVE: To assess the efficacy and safety of subcutaneous injections of Botulinum Toxin Type A (BTA) in treating FPHL. METHODS: Enrolled outpatients with FPHL who exhibited an allergic reaction to minoxidil solution. Diagnosis of FPHL was established through clinical examination and trichoscopy. Inclusion criteria involved patients with no prior treatment within the last year and without any comorbidities. BTA, specifically 100 units, was mixed with 2 mL of 0.9% normal saline. Twenty injection target sites, spaced 2-3 cm apart, were symmetrically marked on the hairless area of the scalp. A dosage of five units was intradermally injected at each target site. Representative photographs and dermoscopic images of the scalp were captured before and after 3 months of treatment. RESULTS: A total of 10 FPHL, aged between 26 and 40 years, were included. The average age was 30.3 ± 4.64 years, and all patients had a positive family history of Androgenetic Alopecia. The average duration of the disease was 3.70 ± 1.42 years. According to patients' self-assessment, after 1 month of treatment, 10 FPHL patients reported experiencing moderate to marked improvement in symptoms related to scalp oil secretion. Three months later, dermatological assessments showed that three had mild improvement, six had no change, and one had a worsening condition. No adverse effects were observed. CONCLUSIONS: Our study suggests that the effectiveness of BTA for FPHL is limited to 3 months. However, it can be considered for tentative use after effective communication with patients. The long-term efficacy and safety of BTA in treating FPHL require further observation and study.
Assuntos
Toxinas Botulínicas Tipo A , Minoxidil , Adulto , Feminino , Humanos , Minoxidil/uso terapêutico , Toxinas Botulínicas Tipo A/efeitos adversos , Alopecia/tratamento farmacológico , Couro CabeludoRESUMO
OBJECTIVE: In this study, the safety and efficacy of scalp repair serum microneedles combined with oral drug administration and topical medication were investigated for the treatment of moderate to severe androgenetic alopecia. METHODS: Twenty patients, consisting of 4 males and 16 females, who sought treatment for moderate to severe androgenetic alopecia at our hair medicine research center alopecia specialty clinic between August and December 2022 were randomly selected for the study. Male patients underwent oral administration of finasteride topical application of 5% minoxidil, and biweekly scalp repair serum microneedle therapy. Female patients were administered spironolactone or Diane-35 orally and applied 2% minoxidil topically, paired with biweekly scalp repair serum microneedle therapy sessions. After seven treatments, the scalp repair serum microneedle was discontinued, but oral administration and topical applications were continued, followed by a 1-month follow-up. Using a hair dermoscopy, hair follicles in a fixed region on the top of the head were manually counted per unit area to evaluate the hair restoration status of the patients quantitatively. RESULTS: All 20 patients completed 3 months of combined therapy and a 1-month follow-up. On average, the patients experienced an increase of 42.6 hairs, with an efficiency rate of 100%. Significant differences were observed in hair count between any two of the first seven treatments (p < 0.001). A significant negative correlation was discovered between the initial pre-treatment hair count and the total improvement of hair (p < 0.001), indicating that the greater the degree of hair loss before treatment, the more pronounced the improvement. CONCLUSION: Scalp repair serum microneedle combined therapy in moderate to severe androgenetic alopecia significantly reduces the number of microneedle treatments required, enhances treatment efficacy, and improves therapeutic outcomes.
Assuntos
Minoxidil , Couro Cabeludo , Humanos , Masculino , Feminino , Minoxidil/uso terapêutico , Alopecia/tratamento farmacológico , Alopecia/induzido quimicamente , Cabelo , Resultado do TratamentoRESUMO
OBJECTIVE: Alopecia areata (AA) is often characterized by sudden onset of patchy hair loss. Topical corticosteroid injection is the most common treatment. This study retrospectively observed the clinical efficacy of microneedle minoxidil combined with triamcinolone acetonide in the treatment of AA. METHODS: A total of 230 patients with AA were selected. The experimental group (n = 120) received physician training and home microneedle treatment with minoxidil combined with triamcinolone acetonide once a week. Topical minoxidil and triamcinolone acetonide were used twice daily at other times. The control group (n = 110) was treated with minoxidil combined with triamcinolone acetonide, twice a day. Cure rate, response rate, SALT, dermatological Quality of Life Index (DLQI), visual analogue (VAS), and cost were assessed at weeks 4 and 12. RESULTS: Treated group SALT score(Severity of Alopecia Tool) remarkable lower than control group after treated 4 and 12 weeks. After 12 weeks treatment, DLQI score of the treated group (1.8 ± 1.67) were significantly lower than those of the control group (2.45 ± 1.88) (p < 0.05). VAS score and adverse reaction between two group showed no significant different (p = 0.823, p = 0.484 respectively). The total cost was 53.93 ± 15.85 in the treatment group and 53.26 ± 11.51 in the control group. There was no significant difference between the two groups (p = 0.72). In the treated group, the complete response rate (CR: 78.33%) and total effective rate (CR+PR: 95%) were significantly higher than those in the control group (CR: 40.91% and CR+PR: 51.82%), with statistically significant differences (p < 0.001). CONCLUSION: Microneedle introduction of minoxidil and triamcinolone acetonide in the treatment of AA is a safe, effective, economical, and convenient method, with few adverse reactions, and has a good application prospect.
Assuntos
Alopecia em Áreas , Humanos , Alopecia em Áreas/tratamento farmacológico , Triancinolona Acetonida/uso terapêutico , Minoxidil/uso terapêutico , Estudos Retrospectivos , Qualidade de Vida , Alopecia/tratamento farmacológico , Resultado do TratamentoRESUMO
Alopecia areata is an autoimmune form of non-scarring hair loss. It is usually characterized by limited areas of hair loss. However, the disease may progress to complete scalp and body hair loss (alopecia totalis, alopecia universalis). In patients with alopecia areata hair loss significantly impacts the quality of life. Children and adolescents with alopecia areata often experience bullying, including physical aggression. The disease severity evaluation tools used in clinical practice are: the Severity of Alopecia Tool (SALT) score and the Alopecia Areata Scale (AAS). A SALT score equal to or greater than 20 constitutes a commonly accepted indication for systemic therapy in alopecia areata. When using the AAS, moderate to severe alopecia areata should be considered a medical indication for systemic treatment. Currently, the only two EMA-approved medications for alopecia areata are baricitinib (JAK 1/2 inhibitor) for adults and ritlecitinib (JAK 3/TEC inhibitor) for individuals aged 12 and older. Both are EMA-approved for patients with severe alopecia areata. Other systemic medications used off-label in alopecia areata include glucocorticosteroids, cyclosporine, methotrexate and azathioprine. Oral minoxidil is considered an adjuvant therapy with limited data confirming its possible efficacy. This consensus statement is to outline a systemic treatment algorithm for alopecia areata, indications for systemic treatment, available therapeutic options, their efficacy and safety, as well as the duration of the therapy.
Assuntos
Alopecia em Áreas , Inibidores de Janus Quinases , Adulto , Adolescente , Criança , Humanos , Alopecia em Áreas/tratamento farmacológico , Qualidade de Vida , Alopecia/tratamento farmacológico , Minoxidil/uso terapêutico , Azatioprina/uso terapêutico , Inibidores de Janus Quinases/uso terapêuticoRESUMO
BACKGROUND: Utilization of low-dose oral minoxidil has increased in recent years in association with several clinical studies that have shown its efficacy in treating androgenetic alopecia (AGA). Objective: To assess dermatology providers' attitudes and recommendation behaviors of oral minoxidil for the treatment of AGA. METHODS: An online survey gauging the professional opinions, prescribing behaviors, and use of oral minoxidil was sent using the Orlando Dermatology Aesthetic and Clinical Conference email listserv which included multiple levels of dermatology practitioners including MD/DOs, NPs, and PAs across the United States. RESULTS: Overall, the survey was sent to 2200 providers, and 201 (9.1%) responses were collected. 81% (n=139) of respondents supported the use of oral minoxidil for AGA. Support varied significantly (P=.03) by providers' number of years in practice with those in practice for greater than 30 years with the least amount of support. 92% of respondents (130, n=141) reported feeling comfortable prescribing oral minoxidil, and 83% (116, n=140) found oral minoxidil to be better than its topical formulation. 78% (108, n=139) felt their patients were satisfied with their results, and 89% (124, n=140) felt oral minoxidil was well tolerated by their patients. CONCLUSIONS: This study found that most prescribers use oral minoxidil as a treatment for AGA and find it to be an effective and tolerable option for patients. Support for oral minoxidil was significantly impacted by providers' years in practice. J Drugs Dermatol. 2024;23(3): doi:10.36849/JDD.7519.
Assuntos
Dermatologia , Minoxidil , Humanos , Minoxidil/efeitos adversos , Alopecia/diagnóstico , Alopecia/tratamento farmacológico , Hábitos , EmoçõesRESUMO
BACKGROUND: Currently, there is only one topical medication approved by the U.S. Food and Drug Administration for alopecia, minoxidil 2.5% and 5%. With limited options, dermatologists often turn to compounding pharmacies for customized topical alopecia medications. OBJECTIVES: (1) to investigate the pricing and availabilities of compounded topical alopecia medications and (2) to investigate the delivery/mail options available. METHODS: 103 dermatological compounding pharmacies in the tri-state area were contacted. Data were collected on the prices of 11 different compounded formulations for alopecia, the highest concentration of minoxidil available, compounding accreditation status, and delivery. RESULTS: The majority (76.7% [79/103]) of pharmacies surveyed were responsive. Mean prices for 60 g or mL of medication were $70.44 for minoxidil 5%, $86.95 for minoxidil 5%/finasteride 0.5%, $159.13 for minoxidil 5%/bimatoprost 0.03%, $141.91 for minoxidil 5%/latanoprost 0.02%, $75.31 for finasteride 0.5%, $204.41 for tacrolimus 0.3%, $220.11 for tacrolimus 0.3%/minoxidil 5%/clobetasol 0.05%, $71.44 for cetirizine 1%, $74.93 for metformin 10%, $4,273.20 for tofacitinib 2%, and $1,840.42 for ruxolitinib 2%. Nearly all (93.5% [72/77]) of the pharmacies reported being able to compound minoxidil higher than the commercially available 5%, while 67.6% (50/74) were able to customize minoxidil to be made with <10% alcohol. Just over half (56.4% [44/78]) of the pharmacies were able to deliver to all tri-state areas. The mean delivery fee of pharmacies was $5.93 (n=77). Almost all of the pharmacies (98.7% [76/77]) claimed to be able to process and deliver medications within a week. If pharmacies were not located in the local vicinity, 44.6% (29/65) used a mailing service. CONCLUSION: This survey serves to expand clinicians' and patients' knowledge of the options and prices of topical compounded medications for alopecia. J Drugs Dermatol. 2024;23(3): doi:10.36849/JDD.7697.
Assuntos
Finasterida , Minoxidil , Estados Unidos , Humanos , Tacrolimo , Alopecia/tratamento farmacológico , Composição de MedicamentosRESUMO
We aimed to determine the efficacy of the various available oral, topical, and procedural treatment options for hair loss in individuals with androgenic alopecia. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of the National Library of Medicine was performed. Overall, 141 unique studies met our inclusion criteria. We demonstrate that many over the counter (e.g. topical minoxidil, supplements, low-level light treatment), prescription (e.g. oral minoxidil, finasteride, dutasteride), and procedural (e.g. platelet-rich plasma, fractionated lasers, hair transplantation) treatments successfully promote hair growth, highlighting the superiority of a multifaceted and individualized approach to management.
Assuntos
Alopecia , Terapia com Luz de Baixa Intensidade , Minoxidil , Plasma Rico em Plaquetas , Humanos , Alopecia/tratamento farmacológico , Alopecia/terapia , Terapia com Luz de Baixa Intensidade/métodos , Minoxidil/uso terapêutico , Finasterida/uso terapêutico , Dutasterida/uso terapêuticoRESUMO
BACKGROUND: Topical minoxidil (TM) has been a cornerstone in treating various hair loss disorders, while low-dose oral minoxidil (LDOM) is emerging as an effective alternative. Despite their widespread use, there is a notable gap in the literature regarding their use in treating scarring alopecia. OBJECTIVE: This study evaluates the efficacy and safety of TM and LDOM in managing scarring alopecia. METHODS: A systematic literature search identified relevant studies on TM and LDOM use in central centrifugal cicatricial alopecia, frontal fibrosing alopecia, lichen planopilaris, and traction alopecia. Key metrics included disease stabilization, hair thickness improvement, hair regrowth, and side effect profiles. RESULTS: Analysis of the selected studies revealed mixed outcomes. Most participants experienced benefits in terms of disease stabilization and hair regrowth with TM and LDOM. The majority of cases reported good tolerability of the treatment, although some side effects were noted. CONCLUSION: TM and LDOM show promise in scarring alopecia treatment, demonstrating benefits in disease stabilization and hair regrowth. Despite these positive indications, the variability in results and reported side effects underline the need for further research to establish their consistent efficacy and safety profiles in scarring alopecia treatment. J Drugs Dermatol. 2024;23(3): doi:10.36849/JDD.7743.
Assuntos
Alopecia , Cicatriz , Minoxidil , Humanos , Alopecia/diagnóstico , Alopecia/tratamento farmacológico , Cicatriz/tratamento farmacológico , Cicatriz/etiologia , Cabelo , Minoxidil/uso terapêuticoRESUMO
A 9-year-old girl presented with slow hair growth and hair thinning since birth. Additionally, she had short stature and abnormally short fingers; genetic testing confirmed the diagnosis of trichorhinophalangeal syndrome (TRPS) type 1. After 4 months of topical minoxidil treatment, hair density and length significantly improved diffusely throughout the scalp without evidence of hypertrichosis. This case underscores the therapeutic potential of topical minoxidil for TRPS, paving the way for improved patient quality of life.
Assuntos
Dedos/anormalidades , Doenças do Cabelo , Síndrome de Langer-Giedion , Minoxidil , Nariz/anormalidades , Qualidade de Vida , Feminino , Humanos , Criança , Minoxidil/uso terapêutico , Cabelo , Alopecia/tratamento farmacológico , Administração Tópica , Resultado do TratamentoRESUMO
BACKGROUND: Female-pattern hair loss (FPHL) is characterized by decreased scalp hair density, thinning of hair shafts, and progressive miniaturization of hair follicles. OBJECTIVE: To compare the safety and efficacy of spironolactone versus bicalutamide in female pattern hair loss [FPHL]. METHODS: The study design was retrospective, and all eligible females aged between 18 years and 50 years with FPHL were included. We identified 120 patients from our database who fulfilled the inclusion and exclusion criteria, and patients were then categorized into two groups, Group A comprising patients who were taking 100 mg of spironolactone once daily and Group B comprising patients who were taking 50 mg of bicalutamide once daily along with topical minoxidil 2% in both groups. Patient were analysed at approximately at 24 weeks from the commencement of the treatment. RESULTS: Mean reduction in hair loss severity score on Sinclair scale was 19.51% in spironolactone group compared to 28.20% in bicalutamide group at 24 weeks, which was statistically significant. On global photographic assessment, marked improvement was seen in bicalutamide group compared to spironolactone group (p = 0.139). CONCLUSIONS: Our study, though limited by its retrospective design and small sample size, showed that bicalutamide has greater efficacy and better safety profile in comparison to spironolactone in the treatment of FPHL.
Assuntos
Alopecia , Anilidas , Nitrilas , Espironolactona , Compostos de Tosil , Humanos , Feminino , Espironolactona/uso terapêutico , Espironolactona/efeitos adversos , Anilidas/efeitos adversos , Anilidas/uso terapêutico , Estudos Retrospectivos , Alopecia/tratamento farmacológico , Adulto , Pessoa de Meia-Idade , Compostos de Tosil/efeitos adversos , Compostos de Tosil/uso terapêutico , Nitrilas/efeitos adversos , Nitrilas/uso terapêutico , Nitrilas/administração & dosagem , Adulto Jovem , Minoxidil/uso terapêutico , Minoxidil/efeitos adversos , Resultado do Tratamento , Adolescente , Índice de Gravidade de DoençaRESUMO
Alopecia, also known as hair loss, is a highly prevalent condition affecting millions of men and women in the United States and worldwide, making it one of the most common complaints by patients presenting to a dermatologist. The symptomology on the presentation of alopecia can be highly variable, ranging from diffuse thinning of hair, discrete and localized patches completely absent of hair, or noticing significant shedding when brushing and showering. Although alopecia does not have a direct negative health impact on patients, it is nonetheless a debilitating disease as it can profoundly impact an individual's self-image and psychosocial well-being. There are multiple treatment options available to patients with alopecia, and they are typically tailored to the patient's needs and preferences. The most common of these is the Food and Drug Administration-approved drugs for alopecia, minoxidil, and finasteride. However, both of these are known to be partially efficacious for all patients, so clinicians often use different modalities in conjunction with them, in particular laser-based therapies. This review article will provide a comprehensive assessment of lasers and other light therapies that may be used to manage the two most common types of alopecia: androgenetic alopecia and alopecia areata.
Assuntos
Alopecia em Áreas , Masculino , Humanos , Feminino , Cabelo , Lasers , Minoxidil/uso terapêuticoRESUMO
It has been recently established that laser treatment can be combined with topical or intralesional medications to enhance the delivery of drugs and improve overall results in a variety of different dermatological disorders. The aim of this review is to evaluate the use of laser and energy-assisted drug delivery (LEADD) for the treatment of alopecia with a specific focus on ablative fractional lasers (AFL), non-ablative fractional lasers (NAFL), and radiofrequency microneedling (RFMN). A comprehensive PubMed search was performed in December 2022 for "laser-assisted drug delivery" as well as "laser" and "alopecia." The evidence regarding LEADD for alopecia treatment is limited to two specific alopecia subtypes: alopecia areata (AA) and androgenetic alopecia (AGA)/pattern hair loss (PHL). LEADD with minoxidil and platelet-rich plasma (PRP) were evaluated for efficacy in both treatments of AA and AGA. LEADD with topical corticosteroids and intralesional methotrexate were studied for the treatment of AA, while LEADD with growth factors and stem cells were studied for the treatment of AGA. Multiple RCTs evaluated LEADD for topical corticosteroids with ablative fractional lasers for the treatment of AA. There is evidence in the literature that supports the use of topical minoxidil in combination with all devices for the treatment of AGA/PHL. All the reviewed studies show a positive treatment effect with LADD; however, some trials did not find LEADD to be superior to monotherapy or microneedling-assisted drug delivery. LEADD is a rapidly emerging treatment modality for the treatment of AGA and AA.
Assuntos
Alopecia em Áreas , Minoxidil , Humanos , Preparações Farmacêuticas , Alopecia em Áreas/tratamento farmacológico , Lasers , CorticosteroidesRESUMO
Laser sources have established their potential effect in inducing hair regrowth. No large cohort study has evaluated the effect of ablative fractional 2940-nm erbium yttrium aluminum garnet (Er: YAG) laser in the treatment of androgenetic alopecia (AGA). To investigate the efficacy and safety of the ablative fractional 2940-nm Er: YAG laser in combination with medication therapy for the treatment of AGA. We performed a retrospective study between first July 2021 to 30th December 2021. All included patients received oral finasteride and topical minoxidil, or combined with six sessions of Er: YAG laser at 2-week intervals. Patients were divided into medication or combined therapy groups. The efficacy of the two therapies was evaluated by the investigator's Global Assessment (IGA) scores and the patient's Likert satisfaction scale at week 12 and week 24. Changes in total, terminal and villous hair count, total and terminal hair diameter, and AGA grade were also recorded. Adverse events were evaluated at each follow-up. A total of 192 male patients with AGA were included, including 67 receiving combination treatment, and 125 receiving medication treatment. At week 24, the combination treatment afforded superior outcomes in the IGA score, patient's global assessment, total and terminal hair counts, and diameters (all P<0.05). No severe adverse events were reported in both groups. The combined therapy of ablative fractional Er: YAG laser and medication was superior in treating male AGA than single medication therapy without serious adverse effects.
Assuntos
Alopecia , Lasers de Estado Sólido , Humanos , Alopecia/terapia , Alopecia/radioterapia , Lasers de Estado Sólido/uso terapêutico , Masculino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Resultado do Tratamento , Finasterida/administração & dosagem , Finasterida/uso terapêutico , Minoxidil/administração & dosagem , Terapia Combinada , Terapia com Luz de Baixa Intensidade/métodos , Terapia com Luz de Baixa Intensidade/efeitos adversos , Terapia com Luz de Baixa Intensidade/instrumentaçãoRESUMO
Androgenetic alopecia is a common type of hair loss, which is generally influenced by genetic factors and systemic androgens resulting in follicular miniaturization.1 It can cause cosmetic problems leading to psychological distress among affected men and women. Effective standard medical treatments available are topical minoxidil 2 to 5%, oral finasteride, oral dutasteride, and hair transplantation.1 However, some patients do not achieve favorable results with standard treatments. For these reasons, other novel treatments have been developed, including new medications, regenerative medicines (autologous platelet-rich plasma, adipose-derived stem cells, micrograft generation, and exosome), and low-level laser therapy.
Assuntos
Terapia com Luz de Baixa Intensidade , Plasma Rico em Plaquetas , Masculino , Humanos , Feminino , Alopecia/tratamento farmacológico , Finasterida/uso terapêutico , Finasterida/efeitos adversos , Minoxidil/uso terapêutico , Minoxidil/efeitos adversos , Resultado do TratamentoRESUMO
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.
Assuntos
Adenosina , Alopecia , Folículo Piloso , Cabelo , Minoxidil , Receptores Androgênicos , Transdução de Sinais , Alopecia/tratamento farmacológico , Alopecia/metabolismo , Alopecia/patologia , Humanos , Masculino , Receptores Androgênicos/metabolismo , Adenosina/metabolismo , Adenosina/farmacologia , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Transdução de Sinais/efeitos dos fármacos , Minoxidil/farmacologia , Feminino , Animais , Cabelo/crescimento & desenvolvimento , Cabelo/efeitos dos fármacos , Cabelo/metabolismoRESUMO
Minoxidil (MIN) is used topically to treat alopecia. However, its low absorption limits its use, warranting a new strategy to enhance its delivery into skin layers. The objective of this study was to evaluate the dermal delivery of MIN by utilizing dissolved microneedles (MNs) loaded with MIN nanosuspension (MIN-NS) for hair regrowth. MIN-NS was prepared by the solvent-antisolvent precipitation technique. The particle size of MIN-NS was 226.7 ± 9.3 nm with a polydispersity index of 0.29 ± 0.17 and a zeta potential of -29.97 ± 1.23 mV. An optimized formulation of MIN-NS was selected, freeze-dried, and loaded into MNs fabricated with sodium carboxymethyl cellulose (Na CMC) polymeric solutions (MIN-NS-loaded MNs). MNs were evaluated for morphology, dissolution rate, skin insertion, drug content, mechanical properties, ex vivo permeation, in vivo, and stability studies. MNs, prepared with 14% Na CMC, were able to withstand a compression force of 32 N for 30 s, penetrate Parafilm M® sheet at a depth of 374-504 µm, and dissolve completely in the skin within 30 min with MIN %recovery of 95.1 ± 6.5%. The release of MIN from MIN-NS-loaded MNs was controlled for 24 h. MIN-NS-loaded MNs were able to maintain their mechanical properties and chemical stability for 4 weeks, when kept at different storage conditions. The in vivo study of the freeze-dried MIN-NS and MIN-NS-loaded MNs proved hair regrowth on rat skin after 11 and 7 days, respectively. These results showed that MIN-NS-loaded MNs could potentially improve the dermal delivery of MIN through the skin to treat alopecia.
Assuntos
Minoxidil , Pele , Ratos , Animais , Administração Cutânea , Alopecia/tratamento farmacológico , Cabelo , Sistemas de Liberação de Medicamentos/métodos , AgulhasRESUMO
Alopecia areata (AA) is an autoimmune-induced hair loss condition, by utilizing MNX, a hair growth-promoting compound. However, minoxidil (MNX) administration's efficacy is hindered by low bioavailability and adverse effects. To enhance its delivery, Trilayer Dissolving Microneedles (TDMN) are introduced, enabling controlled drug release. The study's primary was to establish a validated UV-Vis Spectrophotometer method for Minoxidil analysis in rat skin affected by alopecia areata. This method adheres to International Conference Harmonization (ICH) and FDA guidelines, encompassing accuracy, precision, linearity, quantification limit (QL), and detection limit (DL). The validation method was conducted through two approaches, namely UV region validation using PBS and the colorimetric method in the visible region (Vis). The validated approach is then employed for assessing in vitro release, ex vivo permeation, and in vivo pharmacokinetics. Results indicate superior MNX extraction recovery using methanol compared to acetonitrile. Method C (5mL methanol) is optimal, offering high recovery with minimal solvent usage. Precision assessments demonstrate %RSD values within MNX guidelines (≤15%), affirming accuracy and reproducibility. UV-Vis spectroscopy quantifies MNX integration into TDMN, using PVA-PVP, with concentrations aligning with ICH standards (95% to 105%). In conclusion, TDMN holds promise for enhancing MNX delivery, mitigating bioavailability and side effect challenges. The validated UV-Vis Spectrophotometer method effectively analyzes MNX in skin tissues, providing insights into AA treatment and establishing a robust analytical foundation for future studies.
Assuntos
Alopecia em Áreas , Minoxidil , Animais , Ratos , Minoxidil/uso terapêutico , Alopecia em Áreas/diagnóstico , Alopecia em Áreas/tratamento farmacológico , Colorimetria , Reprodutibilidade dos Testes , Metanol/uso terapêuticoRESUMO
BACKGROUND AND OBJECTIVE: Systemic adverse effects (AE) are a major concern of low-dose oral minoxidil (LDOM) treatment, especially in patients with arterial hypertension or arrhythmia. The objective of this study was to evaluate the safety of LDOM in patients with hypertension or arrhythmia. PATIENTS AND METHODS: Retrospective multicenter study of patients with hypertension or arrhythmia treated with LDOM for any type of alopecia. RESULTS: A total of 254 patients with hypertension [176 women (69.3%) and 78 men (30.7%)] with a mean age of 56.9 years (range 19-82) were included. From them, the dose of LDOM was titrated in 128 patients, allowing the analysis of 382 doses. Patients were receiving a mean of 1.45 (range 0-5) antihypertensive drugs. Systemic AE were detected in 26 cases (6.8%) and included lightheadedness (3.1%), fluid retention (2.6%), general malaise (0.8%), tachycardia (0.8%) and headache (0.5%), leading to LDOM discontinuation in 6 cases (1.5%). Prior treatment with doxazosin (P<0.001), or with three or more antihypertensive drugs (P=0.012) was associated with a higher risk of discontinuation of LDOM. CONCLUSIONS: LDOM treatment showed a favorable safety profile in patients with hypertension or arrhythmia, similar to general population.
Assuntos
Hipertensão , Minoxidil , Masculino , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Minoxidil/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Alopecia/tratamento farmacológico , Alopecia/induzido quimicamente , Hipertensão/tratamento farmacológico , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: Systemic adverse effects (AE) are a major concern of low-dose oral minoxidil (LDOM) treatment, especially in patients with arterial hypertension or arrhythmia. The objective of this study was to evaluate the safety of LDOM in patients with hypertension or arrhythmia. PATIENTS AND METHODS: Retrospective multicenter study of patients with hypertension or arrhythmia treated with LDOM for any type of alopecia. RESULTS: A total of 254 patients with hypertension [176 women (69.3%) and 78 men (30.7%)] with a mean age of 56.9 years (range 19-82) were included. From them, the dose of LDOM was titrated in 128 patients, allowing the analysis of 382 doses. Patients were receiving a mean of 1.45 (range 0-5) antihypertensive drugs. Systemic AE were detected in 26 cases (6.8%) and included lightheadedness (3.1%), fluid retention (2.6%), general malaise (0.8%), tachycardia (0.8%) and headache (0.5%), leading to LDOM discontinuation in 6 cases (1.5%). Prior treatment with doxazosin (P<0.001), or with three or more antihypertensive drugs (P=0.012) was associated with a higher risk of discontinuation of LDOM. CONCLUSIONS: LDOM treatment showed a favorable safety profile in patients with hypertension or arrhythmia, similar to general population.