Hair-Regrowing Potential of Minoxidil Nanocrystal Structure versus Rosemary's Hydroethanolic Extract on C57BL/6 Mice

Document Type : Original Research Article

Authors

1 Department of Biology, Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran

2 Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

4 Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

5 Department of Pharmaceutics, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

10.22034/nmrj.2024.01.010

Abstract

This study aimed to enhance the effectiveness and water solubility of Minoxidil (MXD) by producing its nanocrystal structure, which improves its vasodilator properties and promotes hair growth. In the current study, the hair growth-stimulating activity of the MXD nanoparticles (MXD-NPs) was compared with the hydroethanolic rosemary (RSY) extract on the C57BL/6 mice. The MXD-NPs were produced through a bead mill and ultrasonic process and characterized using various techniques. The cytotoxicity of MXD-NPs was studied on human dermal fibroblasts, and their hair growth-stimulating activity was analyzed in C57BL/6 mice. The results showed that MXD-NPs significantly increased the hair growth rate in mice compared to commercial MXD and hydroethanolic rosemary extract as they were delivered safely and specifically to the target pilosebaceous follicles. The follicular uptake of MXD-NPs was also increased compared to commercial MXD, leading to improved pilosebaceous follicle re-growth and hair growth in treated mice. Therefore, MXD-NPs have the potential to be a safe and efficient iso-formulation structure for hair growth promotion.

Graphical Abstract

Hair-Regrowing Potential of Minoxidil Nanocrystal Structure versus Rosemary's Hydroethanolic Extract on C57BL/6 Mice

Keywords

References

  1. Falto-Aizpurua L, Choudhary S, Tosti A. Emerging treatments in alopecia. Expert Opin Emerg Drugs, 2014;19 (4):545-556.
  2. Rogers NE, Avram MR. Medical treatments for male and female pattern hair loss. Journal of the American Academy of Dermatology, 2008;59 (4):547-566.
  3. Higgins CA, Christiano AM. Regenerative medicine and hair loss: how hair follicle culture has advanced our understanding of treatment options for androgenetic alopecia. Regenerative medicine, 2014;9 (1):101-111.
  4. Al-Attar TS, Kawther K, Al-Neami MA, AbdulSahib WS. Colored asphalt and street print are decorating paving in public spaces. MATEC Web of Conferences, 2018;162:05027.
  5. Mirzaeei S, Pirhayati FH, Mohammadi G, Rahimpour E, Martinez F, Jouyban A. Solubility of minoxidil in binary mixture of ethanol+ water at various temperatures. Physics and Chemistry of Liquids, 2019;57 (6):788-799.
  6. Aljuffali IA, Sung CT, Shen F-M, Huang C-T, Fang J-Y. Squarticles as a lipid nanocarrier for delivering diphencyprone and minoxidil to hair follicles and human dermal papilla cells. The AAPS journal, 2014;16:140-150.
  7. Nagai N, Iwai Y, Sakamoto A, Otake H, Oaku Y, Abe A, Nagahama T. Drug delivery system based on minoxidil nanoparticles promotes hair growth in C57BL/6 mice. International Journal of Nanomedicine, 2019;14:7921.
  8. Desai C. Meyler''s side effects of drugs: The international encyclopedia of adverse drug reactions and interactions. Indian Journal of Pharmacology, 2016;48 (2):224.
  9. Nagai N, Iwai Y, Sakamoto A, Otake H, Oaku Y, Abe A, Nagahama T. Drug delivery system based on minoxidil nanoparticles promotes hair growth in C57BL/6 mice. International Journal of Nanomedicine, 2019:7921-7931.
  10. Oaku Y, Abe A, Sasano Y, Sasaki F, Kubota C, Yamamoto N, Nagahama T, Nagai N. Minoxidil nanoparticles targeting hair follicles enhance hair growth in C57BL/6 mice. Pharmaceutics, 2022;14 (5):947.
  11. Dubey SK, Dey A, Singhvi G, Pandey MM, Singh V, Kesharwani P. Emerging trends of nanotechnology in advanced cosmetics. Colloids and surfaces B: Biointerfaces, 2022;214:112440.
  12. Vañó-Galván S, Camacho F. New treatments for hair loss. Actas Dermo-Sifiliográficas (English Edition), 2017;108 (3):221-228.
  13. Rathnayake D, Sinclair R. Male androgenetic alopecia. Expert Opinion on Pharmacotherapy, 2010;11 (8):1295-1304.
  14. Bassino E, Gasparri F, Munaron L. Protective role of nutritional plants containing flavonoids in hair follicle disruption: A review. International Journal of Molecular Sciences, 2020;21 (2):523.
  15. Rossi A, Cantisani C, Melis L, Iorio A, Scali E, Calvieri S. Minoxidil use in dermatology, side effects and recent patents. Recent patents on inflammation & allergy drug discovery, 2012;6 (2):130-136.
  16. Evron E, Juhasz M, Babadjouni A, Mesinkovska NA. Natural hair supplement: friend or foe? Saw palmetto, a systematic review in alopecia. Skin appendage disorders, 2020;6 (6):329-337.
  17. Oh JY, Park MA, Kim YC. Peppermint oil promotes hair growth without toxic signs. Toxicological research, 2014;30:297-304.
  18. Panahi Y, Taghizadeh M, Marzony ET, Sahebkar A. Rosemary oil vs minoxidil 2% for the treatment of androgenetic alopecia: a randomized comparative trial. Skinmed, 2015;13 (1):15-21.
  19. Micić D, Đurović S, Riabov P, Tomić A, Šovljanski O, Filip S, Tosti T, Dojčinović B, Božović R, Jovanović D. Rosemary essential oils as a promising source of bioactive compounds: Chemical composition, thermal properties, biological activity, and gastronomical perspectives. Foods, 2021;10 (11):2734.
  20. Beloqui A, Solinís MÁ, Rodríguez-Gascón A, Almeida AJ, Préat V. Nanostructured lipid carriers: Promising drug delivery systems for future clinics. Nanomedicine: Nanotechnology, Biology and Medicine, 2016;12 (1):143-161.
  21. Ruela ALM, Perissinato AG, Lino MEdS, Mudrik PS, Pereira GR. Evaluation of skin absorption of drugs from topical and transdermal formulations. Brazilian Journal of Pharmaceutical Sciences, 2016;52:527-544.
  22. Desai PR, Shah PP, Hayden P, Singh M. Investigation of follicular and non-follicular pathways for polyarginine and oleic acid-modified nanoparticles. Pharmaceutical research, 2013;30 (4):1037-1049.
  23. Singh Malik D, Mital N, Kaur G. Topical drug delivery systems: a patent review. Expert opinion on therapeutic patents, 2016;26 (2):213-228.
  24. Sinico C, Fadda AM. Vesicular carriers for dermal drug delivery. Expert opinion on drug delivery, 2009;6 (8):813-825.
  25. Cosco D, Celia C, Cilurzo F, Trapasso E, Paolino D. Colloidal carriers for the enhanced delivery through the skin. Expert opinion on drug delivery, 2008;5 (7):737-755.
  26. Cilurzo F, Chiara Cristiano M, Di Marzio L, Cosco D, Carafa M, Anna Ventura C, Fresta M, Paolino D. Influence of the supramolecular micro-assembly of multiple emulsions on their biopharmaceutical features and in vivo therapeutic response. Current Drug Targets, 2015;16 (14):1612-1622.
  27. Balakrishnan P, Shanmugam S, Lee WS, Lee WM, Kim JO, Oh DH, Kim D-D, Kim JS, Yoo BK, Choi H-G. Formulation and in vitro assessment of minoxidil niosomes for enhanced skin delivery. International journal of pharmaceutics, 2009;377 (1-2):1-8.
  28. Lauterbach A, Müller-Goymann CC. Applications and limitations of lipid nanoparticles in dermal and transdermal drug delivery via the follicular route. European Journal of Pharmaceutics and Biopharmaceutics, 2015;97:152-163.
  29. Jung S, Otberg N, Thiede G, Richter H, Sterry W, Panzner S, Lademann J. Innovative liposomes as a transfollicular drug delivery system: penetration into porcine hair follicles. Journal of Investigative Dermatology, 2006;126 (8):1728-1732.
  30. Jain B, Singh B, Katare OP, Vyas SP. Development and characterization of the minoxidil-loaded liposomal system for delivery to pilosebaceous units. Journal of Liposome Research, 2010;20 (2):105-114.
  31. Toll R, Jacobi U, Richter H, Lademann J, Schaefer H, Blume-Peytavi U. Penetration profile of microspheres in follicular targeting of terminal hair follicles. Journal of Investigative Dermatology, 2004;123 (1):168-176.
  32. Adib ZM, Ghanbarzadeh S, Kouhsoltani M, Khosroshahi AY, Hamishehkar H. The effect of particle size on the deposition of solid lipid nanoparticles in different skin layers: a histological study. Advanced Pharmaceutical Bulletin, 2016;6 (1):31.
  33. Fresta M, Mancuso A, Cristiano MC, Urbanek K, Cilurzo F, Cosco D, Iannone M, Paolino D. Targeting of the pilosebaceous follicle by liquid crystal nanocarriers: In vitro and in vivo effects of the entrapped minoxidil. Pharmaceutics, 2020;12 (11):1127.
  34. Li J-J, Li Z, Gu L-J, Choi K-J, Kim D-S, Kim H-K, Sung C-K. The promotion of hair regrowth by topical application of a Perilla frutescens extract through increased cell viability and antagonism of testosterone and dihydrotestosterone. Journal of natural medicines, 2018;72 (1):96-105.
  35. Lee BH, Lee JS, Kim YC. Hair growth-promoting effects of lavender oil in C57BL/6 mice. Toxicological research, 2016;32:103-108.
  36. Elsayed I, Abdelbary AA, Elshafeey AH. Nanosizing of a poorly soluble drug: technique optimization, factorial analysis, and pharmacokinetic study in healthy human volunteers. International Journal of Nanomedicine, 2014;9:2943.
  37. Ravi PR, Aditya N, Kathuria H, Malekar S, Vats R. Lipid nanoparticles for oral delivery of raloxifene: optimization, stability, in vivo evaluation and uptake mechanism. European Journal of Pharmaceutics and Biopharmaceutics, 2014;87 (1):114-124.
  38. Parhi R, Terapalli BR, Teja B. Formulation and in vitro evaluation of minoxidil topical gel. Turk J Pharm Sci, 2014;11 (2):153-162.
  39. Xiao L, Zhang X, Chen Z, Li J, Li B, Li L. Molecular pathways involved in promoting activity of timosaponin BII on hair growth in C57BL/6 mice. BioMed Research International, 2020;2020.
  40. Zhang Y, Wang J-w, Qu F-z, Zhang Y-m, Su G-y, Zhao Y-q. Hair growth promotion effect of cedrol cream and its dermatopharmacokinetics. RSC advances, 2018;8 (73):42170-42178.
  41. Park S-O, Park B-S, Noh G-Y. Action mechanism of natural plant extracts for hair loss prevention and hair growth promotion in C57BL/6 mice. International Journal Of Pharmacology, 2015;11 (6):588-595.
  42. Rajendran RL, Gangadaran P, Bak SS, Oh JM, Kalimuthu S, Lee HW, Baek SH, Zhu L, Sung YK, Jeong SY. Extracellular vesicles derived from MSCs activate dermal papilla cell in vitro and promotes hair follicle conversion from telogen to anagen in mice. Scientific reports, 2017;7 (1):1-12.
  43. Kwon TR, Oh C, Park H, Han H, Ji H, Kim B. Potential synergistic effects of human placental extract and minoxidil on hair growth‐promoting activity in C 57 BL/6 J mice. Clinical and Experimental Dermatology, 2015;40 (6):672-681.
  44. Aldhalimi MA, Hadi NR, Ghafil FA. Promotive effect of topical ketoconazole, minoxidil, and minoxidil with tretinoin on hair growth in male mice. International Scholarly Research Notices, 2014;2014.
  45. Choi N, Shin S, Song SU, Sung J-H. Minoxidil promotes hair growth through stimulation of growth factor release from adipose-derived stem cells. International Journal of Molecular Sciences, 2018;19 (3):691.
  46. Berger R, Fu J, Smiles K, Turner C, Schnell B, Werchowski K, Lammers K. The effects of minoxidil, 1% pyrithione zinc and a combination of both on hair density: a randomized controlled trial. British Journal of Dermatology, 2003;149 (2):354-362.
  47. Tricarico D, Maqoud F, Curci A, Camerino G, Zizzo N, Denora N, Cutrignelli A, Laquintana V, Lopalco A, la Forgia F. Characterization of minoxidil/hydroxypropyl-β-cyclodextrin inclusion complex in aqueous alginate gel useful for alopecia management: Efficacy evaluation in male rat. European Journal of Pharmaceutics and Biopharmaceutics, 2018;122:146-157.
  48. Chandrashekar B, Nandhini T, Vasanth V, Sriram R, Navale S. Topical minoxidil fortified with finasteride: An account of maintenance of hair density after replacing oral finasteride. Indian dermatology online journal, 2015;6 (1):17.
  49. Mahe YF, Cheniti A, Tacheau C, Antonelli R, Planard‐Luong L, de Bernard S, Buffat L, Barbarat P, Kanoun‐Copy L. Low‐Level Light Therapy Downregulates Scalp Inflammatory Biomarkers in Men With Androgenetic Alopecia and Boosts Minoxidil 2% to Bring a Sustainable Hair Regrowth Activity. Lasers in Surgery and Medicine, 2021;53 (9):1208-1219.
  50. Zappacosta AR. Reversal of baldness in patient receiving minoxidil for hypertension. The New England Journal of Medicine, 1980;303 (25):1480-1481.
  51. Limas CJ, Freis ED. Minoxidil in severe hypertension with renal failure: effect of its addition to conventional antihypertensive drugs. The American journal of cardiology, 1973;31 (3):355-361.
  52. Mehta PK, Mamdani B, Shansky RM, Mahurkar SD, Dunea G. Severe hypertension: Treatment with minoxidil. Jama, 1975;233 (3):249-252.
  53. Boden WE, Korr KS, Bough EW. Nifedipine-lnduced Hypotension and Myocardial Ischemia in Refractory Angina Pectoris. Jama, 1985;253 (8):1131-1135.
  54. Wester RC, Maibach HI, Guy RH, Novak E. Minoxidil stimulates cutaneous blood flow in human balding scalps: pharmacodynamics measured by laser Doppler velocimetry and photopulse plethysmography. Journal of Investigative Dermatology, 1984;82 (5):515-517.
  55. Bunker C, Dowd PM. Alterations in scalp blood flow after the epicutaneous application of 3% minoxidil and 0.1% hexyl nicotinate in alopecia. British Journal of Dermatology, 1987;117 (5):668-669.
  56. Fang C-L, Aljuffali IA, Li Y-C, Fang J-Y. Delivery and targeting of nanoparticles into hair follicles. Therapeutic delivery, 2014;5 (9):991-1006.
  57. Matos BN, Reis TA, Gratieri T, Gelfuso GM. Chitosan nanoparticles for targeting and sustaining minoxidil sulphate delivery to hair follicles. International journal of biological macromolecules, 2015;75:225-229.
  58. Li M, Marubayashi A, Nakaya Y, Fukui K, Arase S. Minoxidil-induced hair growth is mediated by adenosine in cultured dermal papilla cells: possible involvement of sulfonylurea receptor 2B as a target of minoxidil. Journal of Investigative Dermatology, 2001;117 (6).
  59. Lopedota A, Denora N, Laquintana V, Cutrignelli A, Lopalco A, Tricarico D, Maqoud F, Curci A, Mastrodonato M, la Forgia F. Alginate-based hydrogel containing minoxidil/hydroxypropyl-β-cyclodextrin inclusion complex for topical alopecia treatment. Journal of Pharmaceutical Sciences, 2018;107 (4):1046-1054.
  60. Mali N, Darandale S, Vavia P. Niosomes as a vesicular carrier for topical administration of minoxidil: formulation and in vitro assessment. Drug delivery and translational research, 2013;3 (6):587-592.
  61. Mura S, Manconi M, Sinico C, Valenti D, Fadda AM. Penetration enhancer-containing vesicles (PEVs) as carriers for cutaneous delivery of minoxidil. International journal of pharmaceutics, 2009;380 (1-2):72-79.
  62. Mura S, Manconi M, Valenti D, Sinico C, Vila AO, Fadda AM. Transcutol containing vesicles for topical delivery of minoxidil. Journal of drug targeting, 2011;19 (3):189-196.
  63. Zhao Y, Brown MB, Jones SA. The effects of particle properties on nanoparticle drug retention and release in dynamic minoxidil foams. International journal of pharmaceutics, 2010;383 (1-2):277-284.
  64. Uprit S, Sahu RK, Roy A, Pare A. Preparation and characterization of minoxidil loaded nanostructured lipid carrier gel for effective treatment of alopecia. Saudi Pharmaceutical Journal, 2013;21 (4):379-385.
  65. Padois K, Cantiéni C, Bertholle V, Bardel C, Pirot F, Falson F. Solid lipid nanoparticles suspension versus commercial solutions for dermal delivery of minoxidil. International journal of pharmaceutics, 2011;416 (1):300-304.
  66. Aljuffali IA, Sung CT, Shen F-M, Huang C-T, Fang J-Y. Squarticles as a lipid nanocarrier for delivering diphencyprone and minoxidil to hair follicles and human dermal papilla cells. The AAPS journal, 2014;16 (1):140-150.
  67. Blume-Peytavi U, Massoudy L, Patzelt A, Lademann J, Dietz E, Rasulev U, Bartels NG. Follicular and percutaneous penetration pathways of topically applied minoxidil foam. European Journal of Pharmaceutics and Biopharmaceutics, 2010;76 (3):450-453.
  68. Liao A-H, Lu Y-J, Lin Y-C, Chen H-K, Sytwu H-K, Wang C-H. Effectiveness of a layer-by-layer microbubbles-based delivery system for applying minoxidil to enhance hair growth. Theranostics, 2016;6 (6):817.
  69. Lim SH, Kathuria H, Tan JJY, Kang L. 3D printed drug delivery and testing systems—a passing fad or the future? Advanced drug delivery reviews, 2018;132:139-168.
  70. Kathuria H, Li H, Pan J, Lim SH, Kochhar JS, Wu C, Kang L. Large size microneedle patch to deliver lidocaine through skin. Pharmaceutical research, 2016;33 (11):2653-2667.
  71. Kathuria H, Fong MH, Kang L. Fabrication of photomasks consisting microlenses for the production of polymeric microneedle array. Drug delivery and translational research, 2015;5 (4):438-450.
  72. Kathuria H, Kochhar JS, Kang L. Micro and nanoneedles for drug delivery and biosensing. Vol 9: Future Science; 2018:489-492.
Nanomedicine Research Journal
Volume 9, Issue 1
March 2024
Pages 90-102

Files

Share

How to cite

Statistics