1. INTRODUCTION:

Lives are written on faces and skin is a reflection of the age. Skin is very pristine at the time of birth, however, varies with aging. Skin is affected by several factors such as lifestyle, environment pollution, genetics, hormones, and diet. Aging makes skin thin, fragile, wrinkled, hyper-pigmented, and develop crow's feet, deep lines, age spots or sunspots, wrinkles, and fold over time¹ Skin aging is a complex multifactorial biological process involving extrinsic factors that cause photoaging and intrinsic aging involves the degradation of skin tissue structure which is composed of elastin fibers and collagen. Collagen is a building block of skin that forms a 3-dimensional structure and provides strength and tightness to the skin. Aging causes a reduction in collagen and breaking of the bonds between different layers of skin.

This results in skin laxity, rhytids, and wrinkles². Apart from this, facial scars due to depigmentation, acne, and enlarged pores are also distressing. Stretchmarks although physically non-dangerous, are becoming a significant cosmetic concern³. Microneedling offers a minimally invasive, very simple, safe, and effective skin rejuvenation technique to combat facial aging and other skin problems as well⁴. The aim of this study is to review the role of the microneedling technique in treating the skin and reducing the side effects resulting from skin injuries and the influencing factors.

2. MICRONEEDLING DEVICE:

The roller used for microneedling is a Food and Drug Administration (FDA)-approved Class-I, a small hand-held medical device mounted with tiny needles and is intended for at-home use. These needles are made-up of medical-grade metal like steel and are directly rolled over the skin, in different directions to create a controlled depth microchannel. There are 24 circular arrays of eight needles each located on the roller (total 192 needles) in a cylindrical assembly (with 2cm diameter and 2cm length of the cylinder). Each needle tapered with a tip angle of 28° and has a base diameter of 0.2mm⁵ Refer figure 1 for the various options available in the length of needles of microneedling device and the corresponding cosmetology applications for skin rejuvenation. Refer figure 1 for the various options available in the length of needles of microneedling device and the corresponding cosmetology applications for skin rejuvenation.

Up to 0.25 mm needles

Up to 0.5 mm needles

Up to 1 mm needles

Up to 1.5 mm needles

· Painless

· Suitable for delicate skin like around the eyes

· For treating acne scors, pigment spots, wrinkles and fine lines

· For treating deeper scars on the face, and the body.

· Loose skin on the neak.

· For treating cellulite and thick skin like of thighs, upper knee and elbow

Faster post-treatment recovery, very few side effects, and promising clinical results have made microneedling, a valuable cost-effective alternative to other more invasive treatments like laser resurfacing or chemical peeling⁶ There are several varieties of microneedle devices in the current market with varying needle lengths, drum size, and automation⁷ Needle length and corresponding designated application is the most important diverse feature. Roller device type C-8 and MS-4 are special home use devices to be used along with small needle size. A device similar to C-8, however, indicated for the hair-bearing surface like scalp is C-8HE. C-8 models are extremely safe and do not require the prior application of local anesthetics like EMLA, which neither causes any pain or bleeding. Needles 2.0mm and longer are painful and cause little bleeding and therefore are used by practicing dermatologists or other trained professionals. Needles below 2.0mm in length are available for home use, and these are 0.25, 0.5, 1.0, and 1.5mm long. In general, 1mm needles are suitable to treat shallower or less prominent stretch marks, while longer needles are used for more significant and deep scars. 0.25 and 0.5mm needles are recommended for thinner skin scars like crow’s feet, fine lines, pigment, enlarged pores, and scars. You can use the longer needles for deeper scars, however not longer than 1.5mm. Big drums are for larger skin coverage areas for the treatment of stretch marks and gynoid lipodystrophy. In contrast, Derma-stamp is a miniature version of roller for precise treatment of localized scars like chickenpox or varicella scars. It is specifically designed to accommodate a small confined area, which is difficult with bigger drum devices. Their needles are 0.2mm in length with a diameter of only 0.12mm. The procedure with the derma-stamp is quick and can be finished within two minutes⁸ With the right corrective anti-aging serums containing antioxidant vitamins and biomolecules like hyaluronic acid, microneedling prevents the aging process and create a young looking skin. A study involving 20 females in the age group of 32–60 years (average age 53 years) used a C8 model of 196 needles of an average length of 0.13mm arranged in 8 rows for the treatment of melasma (dark discolored patches). All participating women used microneedling at home along with depigmenting serum, every day for 2 months. Although transient redness was observed, no one was required to take time off work and resumes normal activity immediately⁹.

3. MECHANISM OF SKIN REJUVENATION AND THE BENEFITS OF MICRONEEDLING:

Microneedling causes small channels in outermost layer of skin and dermis. This means it creates injury through the use of needles that puncture the skin and in turn stimulate the skin’s natural self-healing cascade. It triggers the release of growth factors, fibroblasts (cells that connect tissues), and elastic fiber formation contributes to skin rejuvenation through neovascularization and neocollagenesis. Skin cells multiply at a faster rate and transform fibroblasts into collagen and elastin fibers. The damaged collagen is removed, new growth takes place, and remodeling of new skin architecture subsequently occurs. Ultimately, this improves the appearance, texture, and feel of the skin. Microneedling causes a significant increase in collagen levels in the skin and also reorganizes the old collagen fibers, by forming new collagen, elastin, and blood capillaries. With the formation of collagen, skin hydration and elasticity are enhanced and wrinkles are less noticeable. Multiplication of the cells in skin capillaries increases branching and thus enhances the blood flow in the dermis. This ultimately results in tight and firm skin, reduced laxity, and enhanced skin lift¹⁰. The most beneficial feature of microneedling is that it does not remove the epidermis nor create open wounds, quick healing is possible. On the contrary, traditional ablative methods like dermabrasion, chemical peels, collagen injections, cortisone-like injections, cryosurgery, and laser resurfacing give undesired post-operative changes and the skin needs significant healing times. Microneedling is an effective procedure with fewer side-effects and is well tolerated¹¹. In ablative methodologies, skin becomes more sensitive to photodamage and may develop dyschromia (skin pigmentation). In contrast, microneedling, being limited to penetration in the epidermis using appropriate length needles, would minimize the risks and negative side effects often noticed with deeper invasive ablation techniques. Without the application of heat or chromophore targets, microneedling provides an excellent safety profile for all skin types.

4. MICRONEEDLING WITH MICRONUTRIENTS AND BIOLOGICALS:

For thousands of years, the obsession of women for a non-invasive method to combat facial aging has fuelled the research and evolution of non-surgical promising tools in skincare. Nowadays, minimally invasive aesthetic procedures are becoming increasingly popular and the physical method; microneedling is the most promising and safe for facial rejuvenation as well as for treatment of some skin problems¹² Cosmetic and biotechnology researchers are constantly developing more and more sophisticated active ingredients designed to neutralize all kinds of skin defects¹³ Therefore, very recently, microneedling technology has been augmented with additional modalities to accelerate facial rejuvenation. It involves the use of micronutrients that act as intense skin rejuvenators and give desirable effects quickly. Examples are Vitamin A/Retinol, vitamin B3, C, and E. These essential vitamins are powerful antioxidants and play important role in collagen formation. Besides, these vitamins improve the viable epidermal thickness, the number of epidermal cell layers, and skin hydration¹⁴. Additionally, biomolecules like Hyaluronic acid substantially plumps up your skin when combined with microneedling. The mechanism of action of these active compounds for skin renewal is scientifically proven. Many research studies have shown that when these vital micronutrients are used along with microneedling, effects are enhanced and better perceived. This is because mechanical puncturing of the skin with thin and tiny needles breaks the skin’s continuity and facilitate penetration into deeper layers of skin. Skin oxidative stress occurs because of frequent or prolonged exposure to aggressors like sunlight, UV radiation, smoke, and pollution¹⁵ It leads to the depletion of the endogenous supply of antioxidant vitamins. Humans are not able to synthesize these vitamins¹⁶

Therefore, skin shows early signs of aging which is a direct reflection of skin damage. Therefore, vitamin containing skincare cosmetics serve as anti-aging and reduce visible signs of oxidative damage. Here are a few specific examples of studies showing the beneficial effects of vitamins with microneedling in skin rejuvenation.

4.1 Vitamin C: Ascorbic acid and its derivatives like Ascorbyl palmitate, Tetrahexyldecyl ascorbate, Ascorbyl tetraisopalmitate.

It helps collagen production in the dermis by increasing fibroblast cell multiplication. It synthesizes collagen namely, I and III, and helps to minimize scars and even stretch marks¹⁷

4.2 Microneedling using vitamin C has reduced severe hyperpigmentation in 30 female patients in just 3 months. The treatment also improved skin texture and brightness¹⁸

4.3 Vitamin A: Retinoic acid and its derivatives like Retinol, Tretinoin, Retinyl palmitate.

Retinyl palmitate therapy along with microneedling has maximized the initial release of growth factors required for skin renewal and stimulated collagen production as well. Almost 80% of patients treated showed improvement in scars (acne, burn, or chickenpox), fine wrinkles, and skin laxity, and the effects were noticeable even after a year of treatment¹⁹ In another study, dermatologists studied microneedling with tretinoin in patients with severe atrophic scars²⁰ This team recommended the use of tretinoin during and again immediately after microneedling as a less invasive and highly effective cosmetic procedure for treating acne scars. Visibly good results were seen even in severe grade 4 scars. The overall treatment was well tolerated without any failure or loss of days at work! All patients were highly satisfied because of minimal downtime and cost-effective treatment.

4.4 Vitamin B3 – Nicotinic acid and its derivatives like niacinamide

Niacinamide successfully reduces rhytides and folds, hyperpigmented spots, and even the tone of the skin. Besides, it also improves elasticity²¹. And can be delivered very effectively into the skin using microneedles (19) A combination of niacinamide and zinc has shown beneficial in reducing the inflammation as observed in the case of acne vulgaris²². As a combination therapy, German Paediatric surgeons carried out microneedling of with ENVIRON (Body oil containing vitamins by Environ SkinCare, in children and adolescents with thermal scars. All the 47 participants (Median age 8.3 years) showed improvement in scar vascularity, pliability, and height²³. This study not only indicates the therapeutic use of microneedling but also assures its safety.

5. BIOLOGICALS:

5.1. Hyaluronic acid:

The application of simple biological agents, such as hyaluronic acid after microneedling creates a dramatic noticeable change in the appearance of the skin. Combination therapy improves firmness, smoothness, and elasticity of the skin making it resistant to wrinkles. ²⁴

5.2. Platelet-rich (PR) fractions:

PR plasma and PR fibrin have high concentrations of platelets and growth factors and are used frequently in dermatology, particularly for hair restoration, skin rejuvenation, acne scars, dermal augmentation, and striae distensae. Furthermore, combination with microneedling produces synergistic effects, leading to improved aesthetic appearance²⁵

6. MICRONEEDLING FOR THE TREATMENT OF STRIAE DISTENSAE:

The continuous change in physical appearance is a matter of concern for new and expecting mothers and, they are most worried about stretch marks. It is an aesthetic problem that eventually affects a woman’s emotional state. Stretch marks are embarrassing, frustrating, and cause cosmetic morbidity and psychological distress. Stretch marks (Striae distansae) narrow, streak-like lines appearing on the skin surface and can be pink, red-violet/purple, or brown²⁶. Some scientists call them as Striae gravidarum²⁷. Stretch marks are very common in pregnancy, affecting almost 80% of pregnant women. Stretch marks not only affect pregnant women. This very common painless skin condition is seen among almost all women between 5 to 50 years, during any part of their lives. Bodybuilders too, get stretch marks on the upper chest and shoulders due to muscle hypertrophy. Faster weight gain during adolescence can bring on stretch marks in both men and women²⁸. Stretch marks, in the beginning (late 2^nd and early 3^rd trimester), appear as flat, pinkish bands (Striae rubra) which slowly become raised, a little longer and wider, and acquire darker color; violet-red. After several months and years, these marks become lighter in color and appear almost white to pale-while (Striae alba) and appear as scar and wrinkled. Stretch marks often cause discomfort and itching of the abdomen, thighs, axillae, and breasts. Because of quick stretching, several changes take place in the skin tissue resulting in disruption of the normal elastic fiber framework. All the skin fibers become thin, short, and disoriented. Thinning of the dermis and a decrease in collagen content in the upper epidermis are the primary reasons responsible for a change in skin texture. Another important skin protein, elastin also undergoes drastic changes affecting skin firmness.

The most common method for treating stretch marks is the application of oils and creams topically. There are many skin cosmetics available commercially in the market, which claim to be helpful in the prevention and/or treatment of stretch marks. To improve the appearance of skin and normalize its texture and elasticity, it is highly essential to increase the collagen content in the skin and stimulate fibroblasts. Fibroblasts are the connective tissue forming cells and help in skin regeneration. Once the fibroblast cells are activated, their job is to produce a 3D structure, rich in Collagen I and Collagen III which provide firmness to the skin and normalize the skin texture. Microneedling increases skin elasticity and blood flow, and skin hydration. These additional processes help to recover the undesirable damage caused due to excessive stretching. It also increases elastin fiber density and reduce the gap between two lines of stretch marks and thus improve the overall appearance²⁹. Korean scientists³⁰ suggested the safe and effective use of microneedling for the treatment of stretch marks after carrying out a study in women. Almost 50% of treated women showed moderate to the excellent effect of microneedling and the rest of the patients showed minimal to moderate improvement in the appearance of stretch marks.

Casabona and Marcese¹⁷studied microneedling with Vitamin C and Calcium hydroxylapatite to reduce the effects of stretch marks. Women with stretch marks on their body were treated thrice with a gap of 1 month between 2 microneedling sessions. Collagen and elastin fibers content were increased in the treated area. The appearance of stretch marks was highly improved and all women were happy and satisfied. Another group of scientists compared microneedling with a CO₂ fractional laser. Microneedling was recommended as a much more superior technique to reduce stretch marks³¹. One more study concluded that microneedling is far more effective than microdermabrasion with sonophoresis. Thus, microneedling offers an easy, safe, and economic method of treating stretch marks³².

7. MICRONEEDLING FOR VITILIGO:

Vitiligo is a depigmenting disorder of the skin and mucous membranes. No satisfactory treatment is available. Therapeutic success also varies depending on the localization of lesions; hands and bony prominent are considered to be resistant to treatment. The disease has a high relapsing rate and patients experience low self-esteem thus negatively affecting the quality of life. A recent study by Ebrahim and Albalate³³. used microneedling with tacrolimus 0.1% ointment in patients with localized and stable vitiligo. The combination was statistically better than either tacrolimus ointment or microneedling alone. Earlier,³³ showed that a combination of microneedling with calcipotriol plus betamethasone is more effective than its combination with tacrolimus for resistant sites. The therapy was well-tolerated and was safe, affordable with minimal side effects.

Khater et al.,³⁴ studied the clinical efficacy of microneedling with 70% trichloroacetic acid in vitiligo applied every 2 weeks for 2 months and found that the treatment was equally effective as that of an intradermal injection of 5-fluorouracil. However, microneedling with 0.005% latanoprost solution could not show a better outcome in resistant vitiligo lesions³⁵. Microneedling with triamcinolone acetonide improved the therapeutic outcomes of narrowband UVB phototherapy in resistant vitiligo patients³⁶.

8. MICRONEEDLING FOR ANDROGENETIC ALOPECIA AND ALOPECIA AREATA:

Androgenic alopecia is a common type of baldness in men³⁷. Alopecia areata an autoimmune disease destroying hair follicles³⁸. Conventional therapy makes use of drugs like finasteride and minoxidil that mainly target the androgens³⁹. Alopecia can occur in the hair on all parts of the body. However, many patients do not respond to these drugs, a significant number of patients go bald despite therapy, and a significant psycho-social impact associated with it. Microneedling induces hair-regrowth by the release growth factors and wound regeneration.

Treatment using finasteride and minoxidil along with microneedling showed an fast response significantly increasing scalp density and boosting new hair follicle stimulation.

Microneedling was found to be safe and a promising tool in hair stimulation and also is useful to treat hair loss refractory to minoxidil therapy in mild to moderate hair loss patients⁴⁴. A man with alopecia areata of ophiasis pattern was treated with clobetasol 0.05% solution, and four treatments of microneedling with triamcinolone over 6 months, showed gradual improvement and complete hair regrowth on the bald area⁴⁰

9. MICRONEEDLING FOR SKIN CANCER

Cancer is one of the deadly diseases in today’s world⁴¹. Naguib et al.,⁴² showed that microneedling improves permeation of poorly permeable 5-fluorouracil through the skin by 4.5 folds thus improving the treatment outcomes in the therapy of superficial basal cell carcinoma and actinic keratosis. Scientists pre-treated the skin with micro needles in a mouse model with B16-F10 melanoma cells implanted in the subcutaneous space underneath which the tumor cells were implanted. Thereafter, marketed 5-fluorouracil topical cream was applied and found to have significantly enhanced permeation and antitumor effects.

10. CONCLUSION:

Skin microneedling regenerates skin very fast through the creation of numerous micro-injuries that emerge when the skin is deeply punctured with very thin needles. The whole procedure induces three major reactions namely, inflammation, proliferation, and re-modeling. It is effective and safe therapeutic modality for numerous skin diseases. More systematic trials are required to generate more information on safety of microneedling for different skin conditions.

11. REFERENCES:

1. Gangale A, Ambore S, Gavit M, Lokhande S. A Pilot Study on Evaluation of Cucumis sativus L. as a Natural Antisolar agent. Research Journal of Pharmacy and Technology. 2016;9(3):212-4.

2. Rittié L, Fisher GJ. Natural and sun-induced aging of human skin. Cold spring harbor perspectives in medicine. 2015;5(1):a015370.

3. Gozali D, Mustarichie R. Hair tonic formulation of anti-alopecia of Angiopteris evecta extract. Research Journal of Pharmacy and Technology. 2019;12(3):1079-85.

4. Khetarpal S, Soh J, Velez MW, Haimovic A. Microneedling. Advances in Cosmetic Surgery. 2019;2(1):47-53.

5. Donnelly RF, Singh TRR, Morrow DI, Woolfson AD. Microneedle-mediated transdermal and intradermal drug delivery. 2012.

6. Alster TS, Graham PM. Microneedling: a review and practical guide. Dermatologic Surgery. 2018;44(3):397-404.

7. Singh A, Yadav S. Microneedling: Advances and widening horizons. Indian dermatology online journal. 2016;7(4):244.

8. McCrudden MT, McAlister E, Courtenay AJ, González‐Vázquez P, Raj Singh TR, Donnelly RF. Microneedle applications in improving skin appearance. Experimental dermatology. 2015;24(8):561-6.

9. Fabbrocini G, De Vita V, Fardella N, Pastore F, Annunziata M, Mauriello M, et al. Skin needling to enhance depigmenting serum penetration in the treatment of melasma. Plastic surgery international. 2011;2011.

10. Iriarte C, Awosika O, Rengifo-Pardo M, Ehrlich A. Review of applications of microneedling in dermatology. Clinical, cosmetic and investigational dermatology. 2017;10:289.

11. Lee JC, Daniels MA, Roth MZ. Mesotherapy, microneedling, and chemical peels. Clinics in Plastic Surgery. 2016;43(3):583-95.

12. Lima EV, Lima MMD, Paixão MP, Miot HA. Assessment of the effects of skin microneedling as adjuvant therapy for facial melasma: a pilot study. BMC dermatology. 2017;17(1):1-6.

13. Silva S, Ferreira M, Oliveira A, Magalhães C, Sousa M, Pinto M, et al. Evolution of the use of antioxidants in anti‐ageing cosmetics. International Journal of Cosmetic Science. 2019;41(4):378-86.

14. Kryczyk-Poprawa A, Kwiecień A, Opoka W. Photostability of topical agents applied to the skin: a review. Pharmaceutics. 2020;12(1):10.

15. Saha D, Tamrakar A, Jana M, Mandal S. Skin Cancer: Dance of Death. Asian Journal of Pharmaceutical Research. 2011;1(2):34-6.

16. Fitzpatrick RE, Rostan EF. Double‐blind, half‐face study comparing topical vitamin C and vehicle for rejuvenation of photodamage. Dermatologic surgery. 2002;28(3):231-6.

17. Casabona G, Marchese P. Calcium hydroxylapatite combined with microneedling and ascorbic acid is effective for treating stretch marks. Plastic and Reconstructive Surgery Global Open. 2017;5(9).

18. Ismail ESA, Patsatsi A, Abd el‐Maged WM, Nada EEDAeA. Efficacy of microneedling with topical vitamin C in the treatment of melasma. Journal of cosmetic dermatology. 2019;18(5):1342-7.

19. Aust MC, Fernandes D, Kolokythas P, Kaplan HM, Vogt PM. Percutaneous collagen induction therapy: an alternative treatment for scars, wrinkles, and skin laxity. Plastic and reconstructive surgery. 2008;121(4):1421-9.

20. Garg S, Baveja S. Combination therapy in the management of atrophic acne scars. Journal of cutaneous and aesthetic surgery. 2014;7(1):18.

21. Wohlrab J, Kreft D. Niacinamide-mechanisms of action and its topical use in dermatology. Skin pharmacology and physiology. 2014;27(6):311-5.

22. Fivenson DP. The mechanisms of action of nicotinamide and zinc in inflammatory skin disease. Cutis. 2006;77(1 Suppl):5-10.

23. Kubiak R, Lange B. Percutaneous collagen induction as an additive treatment for scar formation following thermal injuries: preliminary experience in 47 children. Burns. 2017;43(5):1097-102.

24. Reuther T, Bayrhammer J, Kerscher M. Effects of a three-session skin rejuvenation treatment using stabilized hyaluronic acid-based gel of non-animal origin on skin elasticity: a pilot study. Archives of dermatological research. 2010;302(1):37-45.

25. Gentile RD. Update of Today's Facial Skin Rejuvenation Technology, An Issue of Facial Plastic Surgery Clinics of North America E-Book: Elsevier Health Sciences; 2019.

26. Keller GS. Current Utilization of Biologicals, An Issue of Facial Plastic Surgery Clinics of North America: Elsevier Health Sciences; 2018.

27. Farahnik B, Park K, Kroumpouzos G, Murase J. Striae gravidarum: Risk factors, prevention, and management. International journal of women's dermatology. 2017;3(2):77-85.

28. Wollina U, Goldman A. Management of stretch marks (with a focus on striae rubrae). Journal of cutaneous and aesthetic surgery. 2017;10(3):124.

29. Schwarz M, Laaff H. A prospective controlled assessment of microneedling with the Dermaroller device. Plastic and reconstructive surgery. 2011;127(6):146e-8e.

30. Park KY, Kim HK, Kim SE, Kim BJ, Kim MN. Treatment of striae distensae using needling therapy: a pilot study. Dermatologic surgery. 2012;38(11):1823-8.

31. Khater MH, Khattab FM, Abdelhaleem MR. Treatment of striae distensae with needling therapy versus CO2 fractional laser. Journal of Cosmetic and Laser Therapy. 2016;18(2):75-9.

32. Nassar A, Ghomey S, El Gohary Y, El-Desoky F. Treatment of striae distensae with needling therapy versus microdermabrasion with sonophoresis. Journal of Cosmetic and Laser Therapy. 2016;18(6):330-4.

33. Ibrahim ZA, Hassan GF, Elgendy HY, Al‐shenawy HA. Evaluation of the efficacy of transdermal drug delivery of calcipotriol plus betamethasone versus tacrolimus in the treatment of vitiligo. Journal of Cosmetic Dermatology. 2019;18(2):581-8.

34. Khater M, Nasr M, Salah S, Khattab FM. Clinical evaluation of the efficacy of trichloroacetic acid 70% after microneedling vs intradermal injection of 5‐fluorouracil in the treatment of nonsegmental vitiligo; a prospective comparative study. Dermatologic Therapy. 2020;33(4):e13532.

35. Stanimirovic A, Kovacevic M, Korobko I, Šitum M, Lotti T. Combined therapy for resistant vitiligo lesions: NB‐UVB, microneedling, and topical latanoprost, showed no enhanced efficacy compared to topical latanoprost and NB‐UVB. Dermatologic Therapy. 2016;29(5):312-6.

36. Aboul-Fettouh N, Marzolf S, Smith J, Srivastava D, Nijhawan R, Abuabara K, et al. Index to volume 79. dermatology. 2018;79:400-2.

37. Nikita S, Rashmi PS, Yogendra P, Pranay W, Ankita W, Rai A. Poly Herbal Hair Oil Preparation, Standardization, Treatment and Evaluation for Alopecia in Male Wistar Rats. Research Journal of Pharmacy and Technology. 2019;12(2):757-63.

38. Javeth A, Mathur R, Babu M. A correlational survey to assess the level of stress, coping strategies, and quality of life of female cancer patients related to chemotherapy induced alopecia in Amala Cancer Hospital, Thrissur, Kerala. Asian Journal of Nursing Education and Research. 2017;7(1):1.

39. Kumar N, Singh S, Gupta R. Hair growth activity of Trichosanthes dioica R. leaves. Research Journal of Pharmacognosy and Phytochemistry. 2011;3(1):30-3.

40. Dhurat R, Mathapati, S. (2015). Response to Microneedling Treatment in Men with Androgenetic Alopecia Who Failed to Respond to Conventional Therapy. Indian journal of dermatology, 60(3), 260–263.

41. . Satya Prakash Singh, Vijendra Pratap Singh A Survey Paper for Skin Cancer Detection Based on Retinex Theory Research J Engineering and Tech 2(4): Oct - Dec 2011 page 213-218.

42. Naguib, Y W, Kumar, A, & Cui, Z (2014) The effect of microneedles on the skin permeability and antitumor activity of topical 5-fluorouracil Acta pharmaceutica Sinica B, 4(1), 94–99.

Received on 02.10.2021 Modified on 13.03.2022

Asian J. Res. Pharm. Sci. 2022; 12(3):199-204.

DOI: 10.52711/2231-5659.2022.00035