Lavender essential oil nanoemulsion gel as skin lightener: green formulation, full characterization, anti-melanogenesis effect, and in-vitro/in-vivo safety profile assessment

Document Type : Research Paper

Authors

1 Food Health Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

3 Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

4 Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

5 Student Research Committee, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

6 Molecular Medicine Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

7 Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

8 Department of Pharmaceutics, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

10.22038/nmj.2025.80954.2004

Abstract

Objective(s): In this study, to improve anti-melanogenesis properties, the green method based on an ultrasonic approach was utilized to prepare lavender essential oil (LEO) nanoemulgel.
Material and Methods: Nano-emulsion green preparation, physico-chemical characterization, inspection morphology, animal safety study, cellar toxicity and anti-pigmentation test were performed.
Results: The obtained results showed that with a decline in HLB value (Hydrophilic–lipophilic balance), the mean particle size declined from 157.600±3.798 to 85.566± 2.227 nm (P< 0.05). The evaluations performed with the accelerated stability test (freeze-thaw cycle) showed stability for nanoemulgel. Other factors, such as pH, spreadability, and, viscosity were also measured. In vitro cytotoxicity studies for the revealed LEO-nanoemulsion, on the HFF normal cell line showed less toxicity (73%) than pure LEO. Moreover, LEO-nanoemulsion had a higher cytotoxic impact on B16F10 melanoma cancer cells than pure LEO. The inhibitory activity of this LEO-nanoemulsion was evaluated in melanin content, which indicated that melanin synthesis is more inhibited than LEO. Furthermore, the evaluation of the inhibitory activity presented that the inhibition of L-dopa auto oxidation (87.33± 2.45%) is better than that of LEO (74.22± 3.26%) at a concentration of 5000 µg/ml. It should be noted that no skin irritation was observed with the histo-pathological examination on Wistar rat and the dermal irritation study for the LEO-nanoemulgel.
Conclusion: The results of the present study can be very useful for the introduction and local administration of LEO nanoemulgel for the management of hyperpigmentation conditions.

Keywords


  1. Sonthalia S, Daulatabad D, Sarkar R. Glutathione as a skin whitening agent: facts, myths, evidence and controversies. Indian J Dermatol Venereol Leprol. 2016;82:262.
  2. Hashemi SM, Emami S. Kojic acid-derived tyrosinase inhibitors: synthesis and bioactivity. Pharm Biomed Res. 2015;1(1):1-17.
  3. Noh JM, Kwak SY, Kim DH, Lee YS. Kojic acid–tripeptide amide as a new tyrosinase inhibitor. J Pept Sci: Original Research on Biomolecules. 2007;88(2):300-307.
  4. Silpa-Archa N, Kohli I, Chaowattanapanit S, Lim HW, Hamzavi I. Postinflammatory hyperpigmentation: A comprehensive overview: Epidemiology, pathogenesis, clinical presentation, and noninvasive assessment technique. J Am Acad Dermatol. 2017;77(4):591-605.
  5. James WD, Elston D, Berger T. Andrew's diseases of the skin E-book: clinical dermatology. Elsevier Health Sciences. 2011.
  6. Duarte I, Campos Lage AC. Frequency of dermatoses associated with cosmetics. Contact Dermatitis. 2007;56(4):211-213.
  7. Nicolaidou E, Katsambas AD. Pigmentation disorders: hyperpigmentation and hypopigmentation. Dermatol Clin. 2014;32(1):66-72.
  8. Clardy J, Walsh C. Lessons from natural molecules. Nature. 2004;432(7019):829-837.
  9. Ciocarlan A, Lupascu L, Aricu A, Dragalin I, Popescu V, Geana E-I, et al. Chemical composition and assessment of antimicrobial activity of lavender essential oil and some by-products. Plants. 2021;10(9):1829.
  10. Andrei F, Ersilia A, Tulcan C, Dragomirescu A. Chemical composition and the potential of Lavandula angustifolia L. oil as a skin depigmentant. RecNat Prod. 2018;12(4):340.
  11. Morteza-Semnani K, Saeedi M, Akbari J, Eghbali M, Babaei A, Hashemi SMH, et al. Development of a novel nanoemulgel formulation containing cumin essential oil as skin permeation enhancer. Drug Deliv Transl Res. 2022:1-11.
  12. Anand K, Ray S, Rahman M, Shaharyar A, Bhowmik R, Bera R, et al. Nano-emulgel: emerging as a smarter topical lipidic emulsion-based nanocarrier for skin healthcare applications. Recent Pat Anticancer Drug Discov. 2019;14(1):16-35.
  13. Aziz ZAA, Nasir HM, Ahmad A, Setapar SHM, Ahmad H, Noor MHM, et al. Enrichment of Eucalyptus oil nanoemulsion by micellar nanotechnology: Transdermal analgesic activity using hot plate test in rats’ assay. Sci Rep. 2019;9(1):13678.
  14. Li G, Zhang Z, Liu H, Hu L. Nanoemulsion-based delivery approaches for nutraceuticals: Fabrication, application, characterization, biological fate, potential toxicity and future trends. Food Funct. 2021;12(5):1933-1953.
  15. Raz I, Hasdai D, Seltzer Z, Melmed RN. Effect of hyperglycemia on pain perception and on efficacy of morphine analgesia in rats. Diabetes. 1988;37(9):1253-1259.
  16. Hassanpouraghdam MB, Hassani A, Vojodi L, Asl BH, Rostami A. Essential oil constituents of Lavandula officinalis Chaix. from Northwest Iran. Chemija. 2011;22(3):167-171.
  17. Chao W-W, Su C-C, Peng H-Y, Chou S-T. Melaleuca quinquenervia essential oil inhibits α-melanocyte-stimulating hormone-induced melanin production and oxidative stress in B16 melanoma cells. Phytomedicine. 2017;34:191-201.
  18. Kim HJ, Hong JH. Multiplicative Effects of Essential Oils and Other Active Components on Skin Tissue and Skin Cancers. Int J Mol Sci. 2024;25(10):5397.
  19. Chong W-T, Tan C-P, Cheah Y-K, B. Lajis AF, Habi Mat Dian NL, Kanagaratnam S, et al. Optimization of process parameters in preparation of tocotrienol-rich red palm oil-based nanoemulsion stabilized by Tween80-Span 80 using response surface methodology. PLoS One. 2018;13(8):e0202771.
  20. Fernandes CP, Mascarenhas MP, Zibetti FM, Lima BG, Oliveira RP, Rocha L, et al. HLB value, an important parameter for the development of essential oil phytopharmaceuticals. Rev Bras Farmacogn. 2013;23(1):108-114.
  21. Syed HK, Peh KK. Identification of phases of various oil, surfactant/co-surfactants and water system by ternary phase diagram. Acta Pol Pharm. 2014;71(2):301-309.
  22. Tan SF, Masoumi HRF, Karjiban RA, Stanslas J, Kirby BP, Basri M, et al. Ultrasonic emulsification of parenteral valproic acid-loaded nanoemulsion with response surface methodology and evaluation of its stability. Ultrason Sonochem. 2016;29:299-308.
  23. Mohd Narawi M, Chiu HI, Yong YK, Mohamad Zain NN, Ramachandran MR, Tham CL, et al. Biocompatible nutmeg oil-loaded nanoemulsion as phyto-repellent. Front Pharmacol. 2020;11:214.
  24. Ribeiro RCdA, Barreto SMdAG, Ostrosky EA, Rocha-Filho PA, Veríssimo LM, Ferrari M. Production and characterization of cosmetic nanoemulsions containing Opuntia ficus-indica (L.) Mill extract as moisturizing agent. Molecules. 2015;20(2):2492-2509.
  25. Kundu P, Arora K, Gu Y, Kumar V, Mishra IM. Formation and stability of water‐in‐oil nano‐emulsions with mixed surfactant using in‐situ combined condensation‐dispersion method. Can J Chem Eng. 2019;97(7):2039-2049.
  26. Asmawati, Mustapha WA, Yusop SM, Maskat MY, Shamsuddin AF. Characteristics of cinnamaldehyde nanoemulsion prepared using APV-high pressure homogenizer and ultra turrax. InAIP Conference Proceedings. 2014;1614(1): 244-250. American Institute of Physics.
  27. Tang SY, Shridharan P, Sivakumar M. Impact of process parameters in the generation of novel aspirin nanoemulsions–comparative studies between ultrasound cavitation and microfluidizer. Ultrason Sonochem. 2013;20(1):485-497.
  28. Enayatifard R, Akbari J, Babaei A, Rostamkalaei SS, Hashemi SMH, Habibi E. Anti-microbial potential of nano-emulsion form of essential oil obtained from aerial parts of Origanum Vulgare L. as Food Additive. Adv Pharm Bull. 2021;11(2):327.
  29. Saeedi M, Morteza-Semnani K, Akbari J, Siahposht-Khachaki A, Firouzi M, Goodarzi A, et al. Brain targeting of venlafaxine HCl as a hydrophilic agent prepared through green lipid nanotechnology. J Drug Deliv Sci Technol. 2021;66:102813.
  30. Shah R, Eldridge D, Palombo E, Harding I. Optimisation and stability assessment of solid lipid nanoparticles using particle size and zeta potential. J Phys Sci. 2014;25(1).
  31. Patist A, Bhagwat S, Penfield K, Aikens P, Shah D. On the measurement of critical micelle concentrations of pure and technical‐grade nonionic surfactants. J Surfactants Deterg. 2000;3(1):53-58.
  32. Kakkar V, Mishra AK, Chuttani K, Kaur IP. Proof of concept studies to confirm the delivery of curcumin loaded solid lipid nanoparticles (C-SLNs) to brain. Int J Pharm. 2013;448(2):354-359.
  33. Shinde U, Pokharkar S, Modani S. Design and evaluation of microemulsion gel system of nadifloxacin. Indian J Pharm Sci. 2012;74(3):237.
  34. Bousmina M. Rheology of polymer blends: linear model for viscoelastic emulsions. Rheologica Acta. 1999;38(1):73-83.
  35. Carvalho FC, Barbi MS, Sarmento VHV, Chiavacci LA, Netto FM, Gremião MP. Surfactant systems for nasal zidovudine delivery: structural, rheological and mucoadhesive properties. J Pharm Pharmacol. 2010;62(4):430-439.
  36. Ullah N, Amin A, Alamoudi RA, Rasheed SA, Alamoudi RA, Nawaz A, et al. Fabrication and Optimization of Essential-Oil-Loaded Nanoemulsion Using Box-Behnken Design against Staphylococos aureus and Staphylococos epidermidis Isolated from Oral Cavity. Pharmaceutics. 2022;14(8).
  37. Akbari J, Saeedi M, Enayatifard R, Morteza-Semnani K, Hashemi SMH, Babaei A, et al. Curcumin Niosomes (curcusomes) as an alternative to conventional vehicles: A potential for efficient dermal delivery. Journal of drug delivery science and technology. 2020;60:102035.
  38. Liu P, Boyle AJ, Lu Y, Adams J, Chi Y, Reilly RM, et al. Metal-chelating polymers (MCPs) with zwitterionic pendant groups complexed to trastuzumab exhibit decreased liver accumulation compared to polyanionic MCP immunoconjugates. Biomacromolecules. 2015;16(11):3613-3623.
  39. Ghafelehbashi R, Akbarzadeh I, Yaraki MT, Lajevardi A, Fatemizadeh M, Saremi LH. Preparation, physicochemical properties, in vitro evaluation and release behavior of cephalexin-loaded niosomes. Int J Pharm. 2019;569:118580.
  40. Khoee S, Yaghoobian M. Niosomes: A novel approach in modern drug delivery systems. Nanostructures for drug delivery: Elsevier; 2017; 207-237.
  41. Rigopoulos D, Gregoriou S, Katsambas A. Hyperpigmentation and melasma. J Cosmet Dermatol. 2007;6(3):195-202.
  42. Chen X, Shang S, Yan F, Jiang H, Zhao G, Tian S, et al. Antioxidant activities of essential oils and their major components in scavenging free radicals, inhibiting lipid oxidation and reducing cellular oxidative stress. Molecules. 2023;28(11):4559.
  43. Peng H-Y, Lin C-C, Wang H-Y, Shih Y, Chou S-T. The melanogenesis alteration effects of Achillea millefolium L. essential oil and linalyl acetate: involvement of oxidative stress and the JNK and ERK signaling pathways in melanoma cells. PloS One. 2014;9(4):e95186.
  44. Saeedi M, Morteza-Semnani K, Akbari J, Rahimnia SM, Babaei A, Eghbali M, et al. Eco-friendly preparation, characterization, evaluation of anti-melanogenesis/antioxidant effect and in vitro/in vivo safety profile of kojic acid loaded niosome as skin lightener preparation. J Biomater Sci Polym Ed. 2023;34(14):1952-1980.
  45. Musazzi UM, Franzè S, Minghetti P, Casiraghi A. Emulsion versus nanoemulsion: how much is the formulative shift critical for a cosmetic product? Drug delivery and translational research. 2018;8:414-21.
  46. Trommer H, Neubert R. Overcoming the stratum corneum: the modulation of skin penetration: a review. Skin Pharmacol Physiol. 2006;19(2):106-121.
  47. Mahant S, Kumar S, Nanda S, Rao R. Microsponges for dermatological applications: perspectives and challenges. Asian J Pharm Sci. 2020;15(3):273-291.
  48. Fulton Jr JE, Farzad‐Bakshandeh A, Bradley S. Studies on the mechanism of action of topical benzoyl peroxide and vitamin A acid in acne vulgaris. J Cutan Pathol. 1974;1(5):191-200.
  49. Ammar HO, Salama HA, Ghorab M, Mahmoud AA. Nanoemulsion as a potential ophthalmic delivery system for dorzolamide hydrochloride. AAPS Pharm Sci Tech. 2009;10(3):808-819.
  50. Ammar HO, Salama H, Ghorab M, Mahmoud A. Nanoemulsion as a potential ophthalmic delivery system for dorzolamide hydrochloride. Aaps Pharmscitech. 2009;10:808-819.
  51. Gao W, Jiang Z, Du X, Zhang F, Liu Y, Bai X, et al. Impact of surfactants on nanoemulsions based on fractionated coconut oil: Emulsification stability and in vitro digestion. Journal of Oleo Science. 2020;69(3):227-239.
  52. Sharif HR, Abbas S, Majeed H, Safdar W, Shamoon M, Khan MA, et al. Formulation, characterization and antimicrobial properties of black cumin essential oil nanoemulsions stabilized by OSA starch. Journal of food science and technology. 2017;54:3358-3365.