Search results for: minoxidil

Authors: Sule Pallavi, Shah Priyank, Thavkar Amit, Mehta Suyog, Rohira Poonam

Abstract:

Minoxidil is used topically to help hair growth in the treatment of male androgenetic alopecia. The objective of this study is to compare irritation potential of three conventional formulation of minoxidil 5% topical solution of in human patch test. The study was a single centre, double blind, non-randomized controlled study in 56 healthy adult Indian subjects. Occlusive patch test for 24 hours was performed with three formulation of minoxidil 5% topical solution. Products tested included aqueous based minoxidil 5% (AnasureTM 5%, Sun Pharma, India – Brand A), alcohol based minoxidil 5% (Brand B) and aqueous based minoxidil 5% (Brand C). Isotonic saline 0.9% and 1% w/w sodium lauryl sulphate were included as negative control and positive control respectively. Patches were applied and removed after 24hours. The skin reaction was assessed and clinically scored 24 hours after the removal of the patches under constant artificial daylight source using Draize scale (0-4 points scale for erythema/wrinkles/dryness and for oedema). A combined mean score up to 2.0/8.0 indicates a product is “non-irritant” and score between 2.0/8.0 and 4.0/8.0 indicates “mildly irritant” and score above 4.0/8.0 indicates “irritant”. Follow-up was scheduled after one week to confirm recovery for any reaction. The procedure of the patch test followed the principles outlined by Bureau of Indian standards (BIS) (IS 4011:2018; Methods of Test for safety evaluation of Cosmetics-3rd revision). Fifty six subjects with mean age 30.9 years (27 males and 29 females) participated in the study. The combined mean score (± standard deviation) were: 0.13 ± 0.33 (Brand A), 0.39 ± 0.49 (Brand B), 0.22 ± 0.41 (Brand C), 2.91 ± 0.79 (Positive control) and 0.02 ± 0.13 (Negative control). The mean score of Brand A (Sun Pharma product) was significantly lower than Brand B (p=0.001) and was comparable with Brand C (p=0.21). The combined mean erythema score (± standard deviation) were: 0.09 ± 0.29 (Brand A), 0.27 ± 0.5 (Brand B), 0.18 ± 0.39 (Brand C), 2.02 ± 0.49 (Positive control) and 0.0 ± 0.0 (Negative control). The mean erythema score of Brand A was significantly lower than Brand B (p=0.01) and was comparable with Brand C (p=0.16). Any reaction observed at 24hours after patch removal subsided in a week. All the three topical formulation of minoxidil 5% were non-irritant. Brand A of 5% minoxidil (Sun Pharma) was found to be least irritant than Brand B and Brand C based on the combined mean score and mean erythema score in the human patch test as per the BIS, IS 4011;2018.

Keywords: erythema, irritation, minoxidil, patch test

Procedia PDF Downloads 71

Authors: Joshi Rajiv, Shah Priyank, Thavkar Amit, Rohira Poonam, Mehta Suyog

Abstract:

Topical formulation containing minoxidil and finasteride helps hair growth in the treatment of male androgenetic alopecia. The objective of this study is to compare the irritation potential of three conventional formulations of minoxidil 5% + finasteride 0.1% topical solution of in human patch test. The study was a single centre, double blind, non-randomized controlled study in 53 healthy adult Indian subjects. Occlusive patch test for 24 hours was performed with three formulations of minoxidil 5% + finasteride 0.1% topical solution. Products tested included aqueous based minoxidil 5% + finasteride 0.1% (AnasureTM-F, Sun Pharma, India – Brand A), lipid based minoxidil 5% + finasteride 0.1% (Brand B) and aqueous based minoxidil 5% + finasteride 0.1% (Brand C). Isotonic saline 0.9% and 1% w/w sodium lauryl sulphate were included as negative control and positive control respectively. Patches were applied and removed after 24 hours. The skin reaction was assessed and clinically scored 24 hours after the removal of the patches under constant artificial daylight source using the Draize scale (0-4 points scale for erythema/dryness//wrinkles and for oedema). Follow-up was scheduled after one week to confirm recovery for any reaction. A combined mean score up to 2.0/8.0 indicates a product is “non-irritant” and a score between 2.0/8.0 and 4.0/8.0 indicates “mildly irritant” and a score above 4.0/8.0 indicates “irritant”. The procedure of the patch test followed the principles outlined by the Bureau of Indian Standards (BIS) (IS 4011:2018; Methods of Test for safety evaluation of Cosmetics-3rd revision). Fifty three subjects with mean age 31.9 years (25 males and 28 females) participated in the study. The combined mean score ± standard deviation were: 0.06 ± 0.23 (Brand A), 0.81 ± 0.59 (Brand B), 0.38 ± 0.49 (Brand C), 2.92 ± 0.47 (positive control) and 0.0 ± 0.0 (Negative control). This means the score of Brand A (Sun Pharma product) was significantly lower than that of Brand B (p=0.001) and that of Brand C (p=0.001). The combined mean erythema score ± standard deviation were: 0.06 ± 0.23 (Brand A), 0.81 ± 0.59 (Brand B), 0.38 ± 0.49 (Brand C), 2.09 ± 0.4 (Positive control) and 0.0 ± 0.0 (Negative control). The mean erythema score of Brand A was significantly lower than Brand B (p=0.001) and that of Brand C (p=0.001). Any reaction observed at 24hours after patch removal subsided in a week. All the three topical formulations of minoxidil 5% + finasteride 0.1% were non-irritant. Brand A of minoxidil 5% + finasteride 0.1% (Sun Pharma) was found to be the least irritant than Brand B and Brand C based on the combined mean score and mean erythema score in the human patch test as per the BIS, IS 4011:2018

Keywords: erythema, finasteride, irritation, minoxidil, patch test

Procedia PDF Downloads 51

Authors: Sule Pallavi, Shah Priyank, Thavkar Amit, Rohira Poonam, Mehta Suyog

Abstract:

Introduction: Minoxidil has been used topically for a long time to assist hair growth in the management of male androgenetic alopecia. The aim of this study was a comparative assessment of the irritation potential of three commercial formulations of minoxidil 2% topical solution in a human patch test. Methodology: The study was a non-randomized, double-blind, controlled, single-center study of 56 healthy adult Indian subjects. A 24-hour occlusive patch test was conducted with three formulations of minoxidil 2% topical solution. Products tested were aqueous-based minoxidil 2% (AnasureTM 2%, Sun Pharma, India – Brand A), alcohol-based minoxidil 2% (Brand B) and aqueous-based minoxidil 2% (Brand C). Isotonic saline 0.9% and 1% w/w sodium lauryl sulphate as a negative and positive control, respectively, were included. Patches were applied on the back, followed by removal after 24 hours. The Draize scale (0-4 points scale for erythema/dryness/wrinkles and for oedema) was used to evaluate and clinically score the skin reaction under constant artificial daylight 24 hours after the removal of the patches. The patch test was based on the principles outlined by Bureau of Indian Standards (BIS) (IS 4011:2018; Methods of Test for safety evaluation of Cosmetics-3rd revision). A mean combined score up to 2.0/8.0 indicates that a product is “non-irritant,” and a score between 2.0/8.0 and 4.0/8.0 indicates “mildly irritant” and a score above 4.0/8.0 indicates “irritant”. In case of any skin reaction that was observed, a follow-up was planned after one week to confirm recovery. Results: The 56 subjects who participated in the study had a mean age of 28.7 years (28 males and 28 females). The combined mean score ± standard deviation was: 0.09 ± 0.29 (Brand A), 0.29± 0.53 (Brand B), 0.30 ± 0.46 (Brand C), 3.25 ± 0.77 (positive control) and 0.02 ± 0.13 (negative control). This mean score of Brand A (Sun Pharma) was significantly lower than that of Brand B (p=0.016) and that of Brand C (p=0.004). The mean erythema score ± standard deviation was: 0.09 ± 0.29 (Brand A), 0.27 ± 0.49 (Brand B), 0.30 ± 0.46 (Brand C), 2.5 ± 0.66 (positive control) and 0.02 ± 0.13 (negative control). The mean erythema score of Brand A (Sun Pharma) was significantly lower than that of Brand B (p=0.019) and that of Brand C (p=0.004). Reactions that were observed 24 hours after patch removal subsided in a week’s time. Conclusion: Based on the human patch test as per the BIS, IS 4011:2018, all the three topical formulations of minoxidil 2% were found to be non-irritant. Brand A of 2% minoxidil (Sun Pharma) was found to be the least irritant than Brand B and Brand C based on the combined mean score and mean erythema score.

Keywords: erythema, irritation, minoxidil, patch test

Procedia PDF Downloads 58

Authors: Monica Trifitriana, Rido Mulawarman

Abstract:

Introduction: Androgenetic alopecia (AGA) is a genetically predetermined disorder due to an excessive response to dihydrotestosterone (DHT). Currently, non-surgical treatment of androgenetic alopecia is more in demand by the patient. There are many non-surgical treatments, ranging from topical treatments oral medications, and procedure treatments. Objective: We aim to assess the latest evidence of the efficacy of non-surgical treatments of androgenetic alopecia in men in comparison to placebo for improving hair density, thickness, and growth. Method: We performed a comprehensive search on topics that assess non-surgical treatments of androgenetic alopecia in men from inception up until November 2021. Result: There were 24 studies out of a total of 2438 patients divided into five non-surgical treatment groups to assess the effectiveness of hair growth, namely: minoxidil 2% (MD: 8.11 hairs/cm²), minoxidil 5% (MD: 12.02 hairs/cm²), low-level laser light therapy/LLLT (MD: 12.35 hairs/cm²), finasteride 1mg (MD: 20.43 hairs/cm²), and Platelete-Rich Plasma/PRP with microneedling (MD: 26.33 hairs/cm²). All treatments had significant results for increasing hair growth, particularly in cases of androgenetic alopecia in men (P<0.00001). Conclusion: From the results, it was found that the five non-surgical treatment groups proved to be effective and significant for hair growth, particularly in cases of androgenetic alopecia in men. In order of the best non-surgical treatment for hair growth is starting from PRP with microneedling, Finasteride 1mg, LLLT, minoxidil 5%, to minoxidil 2%.

Keywords: androgenetic alopecia, non-surgical, men, meta-analysis, systematic review

Procedia PDF Downloads 122

Authors: Shivani Dhande, Sanjiv Choudhary, Adarshlata Singh

Abstract:

Introduction: Early age of onset of baldness has marked psychological impact on personality. Combination therapies have better efficacy than monotherapy in androgenetic alopecia. Although medical, surgical treatment and cosmetic aids are available for treatment of pattern baldness, medical is first preferred the line of treatment. Although only 5% topical minoxidil is USFDA approved, 10% is available in India since 2007. Efficacy of tablet finasteride is well established in male pattern baldness. 5% topical minoxidil is effective and safe in female pattern baldness. There is a role of saw palmetto in regrowth of scalp hair. With this background research was undertaken to study efficacy and safety of topical minoxidil 10% + tab. Finesteride (1mg) + dermaroller in male pattern baldness and topical minoxidil 5% + cap. Saw palmetto (320 mg) + dermaroller in female pattern baldness. Methods and Materials: It was a randomized uncontrolled evaluator blind study consisting of total 21 patients, 15 of male pattern baldness and 6 of female pattern baldness within 20-35 yrs of age were enrolled. Male patients had Hamilton grade 2-4 MPB and females had Ludwig grade 2 FPB. Male patients were treated with Tab Finesteride 1mg once daily + 10% topical Minoxidil 1ml twice daily for 6 months. Female patients were treated with Cap. Saw palmetto 320 mg once daily + 5% topical Minoxidil twice daily for 6 months. In both male & female patients dermaroller therapy was used once in 10 days for 4 sittings followed by once in 15 days for next 5 months. Blood pressure and possible side effects were monitored in every follow up visits. Pre and post treatment photographs were taken. Assessment of hair growth was done at baseline and at the end of 6 months. Patients satisfactory grading scale and Physician assessment of hair growth scale were used to assessing the results. Trichoscan was done for assessment of hair-shaft diameter and density. Pre and post treatment photographs and Trichoscan hair growth analysis (by diameter and density) was done by physician (dermatologist) not directly involved in this study (evaluator blind). Result: This combination therapy showed moderate response in female pattern alopecia and good to excellent results in male pattern alopecia at the end of 6 months. During therapy none of the patients showed side effects like hypotension, headache and loss of libido, hirsuitism. Mild irritation due to crystal deposition was noted by 3 patients. Conclusion: Effective and early treatment using combination therapy with higher percent of Minoxidil for rapid hair growth is necessary in initial period since it will boost up the self-confidence in patients leading to better treatment compliance. Subsequent maintenance of hair growth can be done with lower concentration. No significant side effects with treatment are observed in both group of patients.

Keywords: androgenetic alopecia, dermaroller, finasteride, minoxidil, saw palmetto

Procedia PDF Downloads 222

Authors: Hamed Delrobai Ghoochan Atigh

Abstract:

Androgenic alopecia (AGA) is a common form of hair loss, impacting approximately 50% of females, which leads to reduced self-esteem and quality of life. It causes progressive follicular miniaturization in genetically predisposed individuals. Mesotherapy -- a minimally invasive procedure, topical 2% minoxidil, and oral finasteride have emerged as popular treatment options in the realm of cosmetics. However, the efficacy of mesotherapy compared to other options remains unclear. This study aims to assess the effectiveness of mesotherapy when it is added to topical 2% minoxidil treatment on female androgenic alopecia. Mesotherapy, also known as intradermotherapy, is a technique that entails administering multiple intradermal injections of a carefully composed mixture of compounds in low doses, applied at various points in close proximity to or directly over the affected areas. This study involves a randomized controlled trial with 100 female participants diagnosed with androgenic alopecia. The subjects were randomly assigned to two groups: Group A used topical 2% minoxidil twice daily and took Finastride oral tablet. For Group B, 10 mesotherapy sessions were added to the prior treatment. The injections were administered every week in the first month of treatment, every two weeks in the second month, and after that the injections were applied monthly for four consecutive months. The response assessment was made at baseline, the 4th session, and finally after 6 months when the treatment was complete. Clinical photographs, 7-point Likert scale patient self-evaluation, and 7-point Likert scale assessment tool were used to measure the effectiveness of the treatment. During this evaluation, a significant and visible improvement in hair density and thickness was observed. The study demonstrated a significant increase in treatment efficacy in Group B compared to Group A post-treatment, with no adverse effects. Based on the findings, it appears that mesotherapy offers a significant improvement in female AGA over minoxidil. Hair loss was stopped in Group B after one month and improvement in density and thickness of hair was observed after the third month. The findings from this study provide valuable insights into the efficacy of mesotherapy in treating female androgenic alopecia. Our evaluation offers a detailed assessment of hair growth parameters, enabling a better understanding of the treatments' effectiveness. The potential of this promising technique is significantly enhanced when carried out in a medical facility, guided by appropriate indications and skillful execution. An interesting observation in our study is that in areas where the hair had turned grey, the newly regrown hair does not retain its original grey color; instead, it becomes darker. The results contribute to evidence-based decision-making in dermatological practice and offer different insights into the treatment of female pattern hair loss.

Keywords: androgenic alopecia, female hair loss, mesotherapy, topical 2% minoxidil

Procedia PDF Downloads 58

Authors: Li-Yu Lee, Yu-Shuan Chen, Jun Sheng Wang, I-Ming Chu

Abstract:

Microneedle patch is a painless transdermal drug delivery method, It could solve some problems in traditional drug delivery such as digestive system causing drug metabolism and subcutaneous injection causing some side effects. Coating drug on or loading drug in microneedle can carry active ingredient through stratum corneum, also can control dose well when microneedle patch apply on localized topical area. We used hyaluronic acid to fabricate dissolvable microneedle patch and encapsulated minoxidil into microneedles. Minoxdil is a drug for exterior use that can be used to treat Androgenetic alopecia, but related commercial products have some shortcomings, for example, propylene glycol which is used to soften stratum corneum cause skin allergic reaction, comparing chemical promotion, microneedle patch provide physical way to make drugs through nature barrier of skin. In this research, we designed a two-step process to fabricate microneedle patch, that can effectively reduce drug waste, and gentle production process could maintain drug activity well. We also do in vitro test on cadaver to make sure patch has enough mechanical strength to penetrate stratum corneum. In the release test and animal test, we found microneedle patch has higher delivery efficiency than tradition way. In this study, we may determine that germinal MNs patch is a potential commodity.

Keywords: dissolving microneedles, androgenetic alopecia, minoxidil, transdermal drug delivery

Procedia PDF Downloads 241

Authors: Aref Zribi, Sonia Ben Nasr, Sana Fendri, Mahdi Balti, Abderazzek Haddaoui

Abstract:

Background: Despite their benefit, Endocrine therapies (ET) are known to have substantial adverse events (AEs) such as hot flashes, mood disorders and osteoarticular pain. ET induced alopecia(EIA) is less frequently noted by patients and is less reported in the literature. The aim of our study was to report ET alopecia characteristics and their influence on patient and treatment observance. Method: We conducted a retrospective study including luminal BC patients treated in the oncology department of the military hospital of Tunis between January 2015 and December 2020. Patients treated with previous chemotherapy-inducing alopecia were excluded. Results: 145 female patients were included. The median age was 59 years. EIA was reported in 44% of cases. Alopecia was attributed to aromatase inhibitors in 53% and tamoxifen in 21%. Severity was grade 1 in 80% and grade 2 in the remaining cases. ET discontinuation because of alopecia was noted in 6.5 % of patients. Moderate improvement of alopecia was observed with topical minoxidil and Thallium metallicum 9CH homeopathy during ET in 60% of patients. Conclusions: EIA is frequent in BC patients and should be considered to improve treatment observance and patients’ quality of life.

Keywords: endocrine therapy, alopecia, breast cancer, Tunisia

Procedia PDF Downloads 88

Authors: Patricia Mikchaela D. L. Feliciano, Ciela Kadeshka A. Fuentes, Bea Trixia B. Gales, Ethel Princess A. Gepulango, Martin R. Hernandez, Elina Andrea S. Lantion, Jhoe Cynder P. Legaspi, Peter F. Quilala, Gina C. Castro

Abstract:

Propolis is a resin-like material used by bees to fill large gap holes in the beehive. It has been found to possess anti-inflammatory property, which stimulates hair growth in rats by inducing hair keratinocytes proliferation, causing water retention and preventing damage caused by heat, ultraviolet rays, and other microorganisms without abnormalities in hair follicles. The present study aimed to formulate 10% and 30% Propolis Hair Cream for use in enhancing hair properties. Raw propolis sample was tested for heavy metals using Atomic Absorption Spectroscopy; zinc and chromium were found to be present. Likewise, propolis was extracted in a percolator using 70% ethanol and concentrated under vacuum using a rotary evaporator. The propolis extract was analyzed for total flavonoid content. Compatibility of the propolis extract with excipients was evaluated using Differential Scanning Calorimetry (DSC). No significant changes in organoleptic properties, pH and viscosity of the formulated creams were noted after four weeks of storage at 2-8°C, 30°C, and 40°C. The formulated creams were found to be non-irritating based on the Modified Draize Rabbit Test. In vivo efficacy was evaluated based on thickness and tensile strength of hair grown on previously shaved rat skin. Results show that the formulated 30% propolis-based cream had greater hair enhancing properties than the 10% propolis cream, which had a comparable effect with minoxidil.

Keywords: atomic absorption spectroscopy, differential scanning calorimetry (DSC), modified draize rabbit test, propolis

Procedia PDF Downloads 303

Authors: Jung-Il Kang, Jeon Eon Park, Yu-Jin Moon, Young-Seok Ahn, Eun-Sook Yoo, Hee-Kyoung Kang

Abstract:

This study was conducted to evaluate the effect of Undariopsis peterseniana, a seaweed native to Jeju Island, Korea, on the growth of hair. The dermal papilla cells (DPCs) have known to regulate hair growth cycle and length of hair follicle through interact with epithelial cells. When immortalized vibrissa DPCs were treated with the U. peterseniana extract, the U. peterseniana extract significantly increased the proliferation of DPCs. The effect of U. peterseniana extract on the growth of vibrissa follicles was also examined. U. peterseniana extract significantly increased the hair-fiber lengths of the vibrissa follicles. Hair loss is partly caused by dihydrotestosterone (DHT) binding to androgen receptor in hair follicles, and the inhibition of 5α-reductase activity can prevent hair loss through the decrease of DHT level. The U. peterseniana extract inhibited 5α-reductase activity. Minoxidil, a potent hair-growth agent, can induce proliferation in NIH3T3 fibroblasts by opening KATP channels. We thus examined the proliferative effects of U. peterseniana extract in NIH3T3 fibroblasts. U. peterseniana extract significantly increased the proliferation of NIH3T3 fibroblasts. Tetraethylammonium chloride (TEA), a K+ channel blocker, inhibited U. peterseniana-induced proliferation in NIH3T3 fibroblasts. These results suggest that U. peterseniana could have the potential to treat alopecia through the proliferation of DPCs, the inhibition of 5α-reductase activity and the opening of KATP channels. [Acknowledgement] This research was supported by The Leading Human Resource Training Program of Regional Neo industry through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT and future Planning (2016H1D5A1908786).

Keywords: hair growth, Undariopsis peterseniana, vibrissa follicles, dermal papilla cells, 5α-reductase, KATP channels

Procedia PDF Downloads 260

Authors: Chettyparambil Lalchand Thejalakshmi, Sonal Sabu Edattukaran

Abstract:

Hair loss is one of the main issues that contemporary society is dealing with. It can be attributable to a wide range of factors, listing from one's genetic composition and the anxiety we experience on a daily basis. Telogen effluvium [TE] is a condition that causes temporary hair loss after a stressor that might shock the body and cause the hair follicles to temporarily rest, leading to hair loss. Most frequently, women are the ones who bring up these difficulties. Extreme illness or trauma, an emotional or important life event, rapid weight loss and crash dieting, a severe scalp skin problem, a new medication, or ceasing hormone therapy are examples of potential causes. Men frequently do not notice hair thinning with time, but women with long hair may be easily identified when shedding, which can occasionally result in bias because women tend to be more concerned with aesthetics and beauty standards of the society, and approach frequently with the concerns .The woman, who formerly possessed a full head of hair, is worried about the hair loss from her scalp . There are several cases of hair loss reported every day, and Telogen effluvium is said to be the most prevalent one of them all without any hereditary risk factors. While the patient has loss in hair volume, baldness is not the result of this problem . The exponentially growing Dermatology and Aesthetic medical division has discovered that this problem is the most common and also the easiest to cure since it is feasible for these people to regrow their hair, unlike those who have scarring alopecia, in which the follicle itself is damaged and non-viable. Telogen effluvium comes in two different forms: acute and chronic. Acute TE occurs in all the age groups with a hair loss of less than three months, while chronic TE is more common in those between the ages of 30 and 60 with a hair loss of more than six months . Both kinds are prevalent throughout all age groups, regardless of the predominance. It takes between three and six months for the lost hair to come back, although this condition is readily reversed by eliminating stresses. After shedding their hair, patients frequently describe having noticeable fringes on their forehead. The current medical treatments for this condition include topical corticosteroids, systemic corticosteroids, minoxidil and finasteride, CNDPA (caffeine, niacinamide, panthenol, dimethicone, and an acrylate polymer) .Individual terminal hair growth was increased by 10% as a result of the innovative intervention CNDPA. Botulinum Toxin A, Scalp Micro Needling, Platelet Rich Plasma Therapy [PRP], and sessions with Multivitamin Mesotherapy Injections are some recently enhanced techniques with partially or completely reversible hair loss. Also, it has been shown that supplements like Nutrafol and Biotin are producing effective outcomes. There is virtually little evidence to support the claim that applying sulfur-rich ingredients to the scalp, such as onion juice, can help TE patients' hair regenerate.

Keywords: dermatology, telogen effluvium, hair loss, modern hair loass treatments

Procedia PDF Downloads 60

Authors: K. K. Balavenkatraman, B. Bertschi, K. Bigot, A. Grevot, A. Doelemeyer, S. D. Chibout, A. Wolf, F. Pognan, N. Manevski, O. Kretz, P. Swart, K. Litherland, J. Ashton-Chess, B. Ling, R. Wettstein, D. J. Schaefer

Abstract:

Skin toxicity is poorly detected during preclinical studies, and drug-induced side effects in humans such as rashes, hyperplasia or more serious events like bullous pemphigus or toxic epidermal necrolysis represent an important hurdle for clinical development. In vitro keratinocyte-based epidermal skin models are suitable for the detection of chemical-induced irritancy, but do not recapitulate the biological complexity of full skin and fail to detect potential serious side-effects. Normal healthy skin explants may represent a valuable complementary tool, having the advantage of retaining the full skin architecture and the resident immune cell diversity. This study investigated several conditions for the maintenance of good morphological structure after several days of culture and the retention of phase II metabolism for 24 hours in skin explants in vitro. Human skin samples were collected with informed consent from patients undergoing plastic surgery and immediately transferred and processed in our laboratory by removing the underlying dermal fat. Punch biopsies of 4 mm diameter were cultured in an air-liquid interface using transwell filters. Different cultural conditions such as the effect of calcium, temperature and cultivation media were tested for a period of 14 days and explants were histologically examined after Hematoxylin and Eosin staining. Our results demonstrated that the use of Williams E Medium at 32°C maintained the physiological integrity of the skin for approximately one week. Upon prolonged incubation, the upper layers of the epidermis become thickened and some dead cells are present. Interestingly, these effects were prevented by addition of EGFR inhibitors such as Afatinib or Erlotinib. Phase II metabolism of the skin such as glucuronidation (4-methyl umbeliferone), sulfation (minoxidil), N-acetyltransferase (p-toluidene), catechol methylation (2,3-dehydroxy naphthalene), and glutathione conjugation (chlorodinitro benzene) were analyzed by using LCMS. Our results demonstrated that the human skin explants possess metabolic activity for a period of at least 24 hours for all the substrates tested. A time course for glucuronidation with 4-methyl umbeliferone was performed and a linear correlation was obtained over a period of 24 hours. Longer-term culture studies will indicate the possible evolution of such metabolic activities. In summary, these results demonstrate that human skin explants maintain a normal structure for several days in vitro and are metabolically active for at least the first 24 hours. Hence, with further characterisation, this model may be suitable for the study of drug-induced toxicity.

Keywords: human skin explant, phase II metabolism, epidermal growth factor receptor, toxicity

Procedia PDF Downloads 254