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Bicontinuous microemulsions containing Melaleuca alternifolia essential oil as a therapeutic agent for cutaneous wound healing

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Abstract

The Melaleuca alternifolia essential oil (MEO) has been widely used due to its healing and antimicrobial action. Its incorporation into drug delivery systems is a reality, and numerous studies have already been developed for this purpose. In this regard, the aim of this work was to develop, characterize, and evaluate the in vivo pharmacological activity of bicontinuous microemulsions (BME) containing MEO. Through diagram construction, a formulation consisting of Kolliphor® HS 15 (31.05%), Span® 80 (3.45%), isopropyl myristate (34.5%), and distilled water (31%) was selected and MEO was incorporated in the proportion of 3.45% (v/v). Morphological analysis characterization confirms that the system studied herein is a BME. The evaluated formulation showed physicochemical characteristics that allow its topical use. Rheologically, samples were characterized as pseudo-plastic non-Newtonian thixotropic fluids. The chromatographic method developed is in accordance with the current recommendations. The extraction method used assured a 100% recovery of the pharmacological marker (terpinen-4-ol). In vivo studies suggest that BME loaded with MEO may contribute to the healing process of skin wounds. In addition, it demonstrated antibacterial activity for Gram-positive and Gram-negative bacteria. Therefore, the BME system loaded with MEO is promising as a healing and antimicrobial agent for skin wounds.

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References

  1. Constantinides PP, Yiv SH. Particle size determination of phase-inverted water-in-oil microemulsions under different dilution and storage conditions. Int J Pharm. 1995;115:225–34.

    Article  CAS  Google Scholar 

  2. Damasceno BPGL, Silva JA, Oliveira EE, Silveira WLL, Araújo IB, Oliveira AG, et al. Microemulsão: Um promissor carreador para moléculas insolúveis. Rev Ciencias Farm Basica e Apl. 2011;32:9–18.

    CAS  Google Scholar 

  3. Formariz TP, Sarmento VHV, Silva-Junior AA, Scarpa MV, Santilli CV, Oliveira AG. Doxorubicin biocompatible O/W microemulsion stabilized by mixed surfactant containing soya phosphatidylcholine. Colloids Surf B. 2006;51:54–61.

    Article  CAS  Google Scholar 

  4. Rai VK, Mishra N, Yadav KS, Yadav NP. Nanoemulsion as pharmaceutical carrier for dermal and transdermal drug delivery: formulation development, stability issues, basic considerations and applications. J Control Release. 2018;270:203–25.

    Article  CAS  PubMed  Google Scholar 

  5. de Oliveira Neves JK, Apolinário AC, Saraiva KLA, Silva DTC, de Freitas Araújo Reis MY, de Lima Damasceno BPG, et al. Microemulsions containing Copaifera multijuga Hayne oil-resin: challenges to achieve an efficient system for β-caryophyllene delivery. Ind Crop Prod. 2018;111:185–92.

    Article  CAS  Google Scholar 

  6. Singh Y, Meher JG, Raval K, Khan FA, Chaurasia M, Jain NK, et al. Nanoemulsion: concepts, development and applications in drug delivery. J Control Release. 2017;252:28–49.

    Article  CAS  PubMed  Google Scholar 

  7. Yin YM, De Cui F, Mu CF, Choi MK, Kim JS, Chung SJ, et al. Docetaxel microemulsion for enhanced oral bioavailability: preparation and in vitro and in vivo evaluation. J Control Release. 2009;140:86–94.

    Article  CAS  PubMed  Google Scholar 

  8. Pradhan M, Singh D, Singh MR. Novel colloidal carriers for psoriasis: current issues, mechanistic insight and novel delivery approaches. J Control Release. 2013;170:380–95.

    Article  CAS  PubMed  Google Scholar 

  9. Moangella K, De Assis A, Ivyna R, Rêgo DA, De Melo DF, Silva M, et al. Therapeutic potential of Melaleuca alternifolia essential oil in new drug delivery systems. Curr Pharm Des. 2020;26:1–8.

    Article  CAS  Google Scholar 

  10. Guimarães GP, de Freitas Araújo Reis MY, da Silva DTC, Mendonça Junior FJB, Converti A, Pessoa A, et al. Antifungal activity of topical microemulsion containing a thiophene derivative. Braz J Microbiol. 2014;45:545–50.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Flores FC, De Lima JA, Da Silva CR, Benvegnú D, Ferreira J, Burger ME, et al. Hydrogels containing nanocapsules and nanoemulsions of tea tree oil provide antiedematogenic effect and improved skin wound healing. J Nanosci Nanotechnol. 2015;15:800–9.

    Article  CAS  PubMed  Google Scholar 

  12. Flores FC, Ribeiro RF, Ourique AF, Rolim CMB, De Bona Da Silva C, Pohlmann AR, et al. Nanostructured systems containing an essential oil: protection against volatilization. Quim Nova. 2011;34:968–72.

    Article  CAS  Google Scholar 

  13. Kaur G, Mehta SK. Developments of polysorbate (Tween) based microemulsions: preclinical drug delivery, toxicity and antimicrobial applications. Int J Pharm. 2017;529:134–60.

    Article  CAS  PubMed  Google Scholar 

  14. Lapteva M, Kalia YN. Microstructured bicontinuous phase formulations: their characterization and application in dermal and transdermal drug delivery. Expert Opin Drug Deliv. 2013;10:1043–59.

    Article  CAS  PubMed  Google Scholar 

  15. Oliveira ACM, Fontana A, Negrini TC, Nogueira MNM, Bedran TBL, Andrade CR, et al. Emprego do óleo de Melaleuca alternifolia Cheel (Myrtaceae) na odontologia: Perspectivas quanto à utilização como antimicrobiano alternativo às doenças infecciosas de origem bucal. Rev Bras Plantas Med. 2011;13:492–9.

    Article  Google Scholar 

  16. Pazyar N, Yaghoobi R, Rafiee E, Mehrabian A, Feily A. Skin wound healing and phytomedicine: a review. Skin Pharmacol Physiol. 2014;27:303–10.

    Article  CAS  PubMed  Google Scholar 

  17. Pazyar N, Yaghoobi R, Bagherani N, Kazerouni A. A review of applications of tea tree oil in dermatology. Int J Dermatol. 2013;52:784–90.

    Article  CAS  PubMed  Google Scholar 

  18. Pazyar N, Yaghoobi R. Tea tree oil as a novel antipsoriasis weapon. Skin Pharmacol Physiol. 2012;25:162–3.

    Article  CAS  PubMed  Google Scholar 

  19. Chin KB, Cordell B. The effect of tea tree oil (Melaleuca alternifolia) on wound healing using a dressing model. J Altern Complement Med. 2013;19:942–5.

    Article  PubMed  Google Scholar 

  20. Mertas A, Garbusińska A, Szliszka E, Jureczko A, Kowalska M, Król W. The influence of tea tree oil (Melaleuca alternifolia) on fluconazole activity against fluconazole-resistant candida albicans strains. Biomed Res Int. Hindawi Publishing Corporation. 2015;2015:590470.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Groot AC, Schmidt E. Tea tree oil: contact allergy and chemical composition. Contact Dermatitis. 2016;75:129–43.

    Article  CAS  PubMed  Google Scholar 

  22. Lahkar S, Das MK, Bora S. An overview on tea tree (Melaleuca Alternifolia) oil. Int J Pharm Phytopharm Res. 2013;6084:1–16.

    Google Scholar 

  23. Augustine R, Rehman SRU, Ahmed R, Zahid AA, Sharifi M, Falahati M, et al. Electrospun chitosan membranes containing bioactive and therapeutic agents for enhanced wound healing. Int J Biol Macromol. 2020;156:153–70.

    Article  CAS  PubMed  Google Scholar 

  24. Sylvester MA, Amini F, Keat TC. Materials today: Proceedings Electrospun nanofibers in wound healing. Mater Today Proc. Elsevier Ltd; 2020.

  25. Kant V, Jangir BL, Kumar V. Gross and histopathological effects of dimethyl sulfoxide on wound healing in rats. Wound Med [Internet]. Elsevier B.V.; 2020;100194. Available from: https://doi.org/10.1016/j.phrs.2020.104743

  26. Gould L, Abadir P, Brem H, Carter M, Conner-Kerr T, Davidson J, et al. Chronic wound repair and healing in older adults: current status and future research Lisa. J Am Geriatr Soc. 2015;63:427–38.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Moeini A, Pedram P, Makvandi P, Malinconico M, Gomez d’Ayala G. Wound healing and antimicrobial effect of active secondary metabolites in chitosan-based wound dressings: a review. Carbohydr Polym [Internet]. Elsevier; 2020;233:115839. Available from: https://doi.org/10.1016/j.carbpol.2020.115839

  28. Aghajani A, Kazemi T, Enayatifard R, Amiri FT, Narenji M. Investigating the skin penetration and wound healing properties of niosomal pentoxifylline cream. Eur J Pharm Sci [Internet]. Elsevier; 2020;151:105434. Available from: https://doi.org/10.1016/j.ejps.2020.105434

  29. Yadav E, Kumar S, Mahant S, Khatkar S, Rao R. Tea tree oil: a promising essential oil. J Essent Oil Res. 2017;29:201–13.

    Article  CAS  Google Scholar 

  30. Souza Silveira Valente J, Oliveira da Silva Fonseca A, Brasil CL, Sagave L, Flores FC, de Bona da Silva C, et al. In vitro activity of Melaleuca alternifolia (tea tree) in its free oil and nanoemulsion formulations against Pythium insidiosum. Mycopathologia. 2016;181:865–9.

    Article  PubMed  CAS  Google Scholar 

  31. Cavalcanti ALM, Reis MYFA, Silva GCL, Ramalho ÍMM, Guimarães GP, Silva JA, et al. Microemulsion for topical application of pentoxifylline: in vitro release and in vivo evaluation. Int J Pharm. 2016;506:351–60.

    Article  CAS  PubMed  Google Scholar 

  32. Mahdi ES, Sakeena MH, Abdulkarim MF, Abdullah GZ, Sattar MA, Noor AM. Effect of surfactant and surfactant blends on pseudoternary phase diagram behavior of newly synthesized palm kernel oil esters. Drug Des Devel Ther. 2011;5:311–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Li X, He G, Zheng W, Xiao G. Study on conductivity property and microstructure of TritonX-100/alkanol/n-heptane/water microemulsion. Colloids Surf A Physicochem Eng Asp. 2010;360:150–8.

    Article  CAS  Google Scholar 

  34. Zhang J, Michniak-Kohn B. Investigation of microemulsion microstructures and their relationship to transdermal permeation of model drugs: ketoprofen, lidocaine, and caffeine. Int J Pharm. 2011;421:34–44.

    Article  CAS  PubMed  Google Scholar 

  35. Sintov AC, Levy HV, Botner S. Systemic delivery of insulin via the nasal route using a new microemulsion system: in vitro and in vivo studies. J Control Release. 2010;148:168–76.

    Article  CAS  PubMed  Google Scholar 

  36. Soliman SM, Abdel Malak NS, El-Gazayerly ON, Abdel Rehim AA. Formulation of microemulsion gel systems for transdermal delivery of celecoxib: in vitro permeation, anti-inflammatory activity and skin irritation tests. Drug Discov Ther. 2010;4:459–71.

    CAS  PubMed  Google Scholar 

  37. Tao J, Zhu Q, Qin F, Wang M, Chen J, Zheng ZP. Preparation of steppogenin and ascorbic acid, vitamin E, butylated hydroxytoluene oil-in-water microemulsions: characterization, stability, and antibrowning effects for fresh apple juice. Food Chem. Elsevier Ltd. 2017;224:11–8.

    Article  CAS  PubMed  Google Scholar 

  38. Sonia K, Anupama D. Microemulsion based transdermal drug delivery of tea tree oil. Int J Drug Dev Res. 2011;3:191–8.

    Google Scholar 

  39. Wang X, Ge J, Tredget EE, Wu Y. The mouse excisional wound splinting model, including applications for stem cell transplantation. Nat Protoc. 2013;8:302–9.

    Article  CAS  PubMed  Google Scholar 

  40. Weinheimer-Haus EM, Mirza RE, Koh TJ. Nod-like receptor protein-3 inflammasome plays an important role during early stages of wound healing. PLoS One. 2015;10:1–13.

    Article  CAS  Google Scholar 

  41. Ciarlillo D, Celeste C, Carmeliet P, Boerboom D, Theoret C. A hypoxia response element in the Vegfa promoter is required for basal Vegfa expression in skin and for optimal granulation tissue formation during wound healing in mice. PLoS One. 2017;12:1–14.

    Article  CAS  Google Scholar 

  42. Gupta M, Poonawala T, Farooqui M, Ericson ME, Gupta K. Topical fentanyl stimulates healing of ischemic wounds in diabetic rats. J Diabetes. 2015;7:573–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Tang J, Liu H, Gao C, Mu L, Yang S, Rong M, et al. A small peptide with potential ability to promote wound healing. PLoS One. 2014;9:e92082.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Kolumam G, Wu X, Lee WP, Hackney JA, Zavala-Solorio J, Gandham V, et al. IL-22R ligands IL-20, IL-22, and IL-24 promote wound healing in diabetic db/db mice. PLoS One. 2017;12:1–20.

    Article  CAS  Google Scholar 

  45. Medeiros ML, Araújo-Filho I, da Silva EMN, de Sousa Queiroz WS, Soares CD, de Carvalho MGF, et al. Effect of low-level laser therapy on angiogenesis and matrix metalloproteinase-2 immunoexpression in wound repair. Lasers Med Sci. 2017;32:35–43.

    Article  PubMed  Google Scholar 

  46. Lamaisakul S, Tantituvanont A, Lipipun V, Ritthidej G. Development of novel cationic microemulsion as parenteral adjuvant for influenza vaccine. Asian J Pharm Sci. Elsevier B.V.; 2019;0–42.

  47. Inactive Ingredient Search for Approved Drug Products. 2020.

  48. Bardhan S, Kundu K, Saha SK, Paul BK. Physicochemical studies of mixed surfactant microemulsions with isopropyl myristate as oil. J Colloid Interface Sci. 2013;402:180–9.

    Article  CAS  PubMed  Google Scholar 

  49. Grampurohit N, Ravikumar P, Mallya R. Microemulsions for topical use- a review. Indian J Pharm Educ Res. 2011;45:100–7.

    Google Scholar 

  50. Rutherford T, Nixon R, Tam M, Tate B. Allergy to tea tree oil: retrospective review of 41 cases with positive patch tests over 4.5 years. Australas J Dermatol. 2007;48:83–7.

    Article  PubMed  Google Scholar 

  51. Riley TV, Carson CF, Hammer KA. Melaleuca alternifolia (Tea Tree) Oil: a review of antimicrobial and other medicinal properties. Clin Microbiol Rev. 2006;19:50–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Monteiro MH, de Macedo H, da Silva JA, Paumgartten F. Óleos essenciais terapêuticos obtidos de espécies de Melaleuca L. (Myrtaceae Juss.). Rev Fitos. 2013;8:19–32.

    Article  Google Scholar 

  53. Fonseca-Santos B, Del Nero Pacheco C, Pinto MC, Chorilli M. An effective mosquito-repellent topical product from liquid crystal-based tea tree oil. Ind Crops Prod [Internet]. Elsevier; 2019;128:488–95. Available from: https://doi.org/10.1016/j.indcrop.2018.11.020

  54. Song F, Xu J, Hou WG. Surfactant-free oil/water and bicontinuous microemulsion composed of benzene, ethanol and water. Chin Chem Lett. 2010;21:880–3.

    Article  CAS  Google Scholar 

  55. Podlogar F, Gašperlin M, Tomšič M, Jamnik A, Rogač MB. Structural characterisation of water-Tween 40®/Imwitor 308®-isopropyl myristate microemulsions using different experimental methods. Int J Pharm. 2004;276:115–28.

    Article  CAS  PubMed  Google Scholar 

  56. Roohpour N, Wasikiewicz JM, Moshaverinia A, Paul D, Rehman IU, Vadgama P. Isopropyl myristate-modified polyether-urethane coatings as protective barriers for implantable medical devices. Materials (Basel). 2009;2:719–33.

    Article  CAS  PubMed Central  Google Scholar 

  57. Chaiyana W, Rades T, Okonogi S. Characterization and in vitro permeation study of microemulsions and liquid crystalline systems containing the anticholinesterase alkaloidal extract from Tabernaemontana divaricata. Int J Pharm. 2013;452:201–10.

    Article  CAS  PubMed  Google Scholar 

  58. Goebel ASB, Neubert RHH, Wohlrab J. Dermal targeting of tacrolimus using colloidal carrier systems. Int J Pharm. 2011;404:159–68.

    Article  CAS  PubMed  Google Scholar 

  59. Bruxel F, Laux M, Wild LB, Fraga M, Koester LS, Teixeira HF. Nanoemulsions as prospective drug delivery systems. Quim Nova. 2014;35:1827–40.

    Article  Google Scholar 

  60. Patel HK, Barot BS, Parejiya PB, Shelat PK, Shukla A. Topical delivery of clobetasol propionate loaded microemulsion based gel for effective treatment of vitiligo - part II: rheological characterization and in vivo assessment through dermatopharmacokinetic and pilot clinical studies. Colloids Surf B. 2014;119:145–53.

    Article  CAS  Google Scholar 

  61. Das S, Ng WK, Tan RBH. Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers: II. Evaluation of the imidazole antifungal drug-loaded nanoparticle dispersions and their gel formulations. Nanotechnology. 2014;25.

  62. dos Santos WB, Araujo MGS, da Silva JC, Bernardo THL, de Assis Bastos ML, RCSS V. Microbiota Infectante De Feridas Cirúrgicas: Análise Da Produção Científica Nacional E Internacional. Rev SOBECC. 2016;21:46.

    Article  Google Scholar 

  63. Daltin D Tensoativos. 2011.

  64. Callender SP, Mathews JA, Kobernyk K, Wettig SD. Microemulsion utility in pharmaceuticals: implications for multi-drug delivery. Int J Pharm Amsterdam. 2017;526:425–42.

    Article  CAS  Google Scholar 

  65. Biju SS, Ahuja A, Khar RK. Tea tree oil concentration in follicular casts after topical delivery: determination by high-performance thin layer chromatography using a perfused bovine udder model. J Pharm Sci. 2005;94:240–5.

    Article  CAS  PubMed  Google Scholar 

  66. Batista EKF, Costa KKS, Sá E, Viana GEN, Sousa JM, Batista MCS. Avaliação do efeito de formulações com o látex da Euphorbia tirucalli na terapêutica tópica de feridas cutâneas: Aspectos clínicos e histopatológicos. Med Vet. 2014;8:1–11.

    Google Scholar 

  67. Low WL, Martin C, Hill DJ, Kenward MA. Antimicrobial efficacy of liposome-encapsulated silver ions and tea tree oil against pseudomonas aeruginosa, staphylococcus aureus and candida albicans. Lett Appl Microbiol. 2013;57:33–9.

    Article  CAS  PubMed  Google Scholar 

  68. Flores FC, de Lima JA, Ribeiro RF, Alves SH, Rolim CMB, Beck RCR, et al. Antifungal activity of nanocapsule suspensions containing tea tree oil on the growth of Trichophyton rubrum. Mycopathologia. 2013;175:281–6.

    Article  CAS  PubMed  Google Scholar 

  69. Gujjar M, Banga AK. Vehicle influence on permeation through intact and compromised skin. Int J Pharm. 2014;472:362–8.

    Article  CAS  PubMed  Google Scholar 

  70. Cross SE, Russell M, Southwell I, Roberts MS. Human skin penetration of the major components of Australian tea tree oil applied in its pure form and as a 20% solution in vitro. Eur J Pharm Biopharm. 2008;69:214–22.

    Article  CAS  PubMed  Google Scholar 

  71. Lee CJ, Chen LW, Chen LG, Chang TL, Huang CW, Huang MC, Wang CC Correlations of the components of tea tree oil with its antibacterial effects and skin irritation. J Food Drug Anal [Internet]. Elsevier Ltd; 2013;21:169–76. Available from: https://doi.org/10.1016/j.jfda.2013.05.007

  72. Mozelsio NB, Harris KE, McGrath KG, Grammer LC. Immediate systemic hypersensitivity reaction associated with topical application of Australian tea tree oil. Allergy Asthma Proc. 2003;24:73–5.

    PubMed  Google Scholar 

  73. Silva LL, Almeida R, Verícimo MA, Macedo HW, Castro HC. Atividades terapêuticas do óleo essencial de melaleuca (melaleuca alternifolia) Uma revisão de literatura. Brazilian J Heal Rev. 2019;2:6011–21.

    Article  Google Scholar 

  74. Wu Q, Guo T, Li J. Study on the antibacterial activity and promoting skin wound healing activities of tea tree oil nanoemulsion. Hans J Food Nutr Sci. 2020;09:114–20.

    Article  Google Scholar 

  75. Ghosh V, Saranya S, Mukherjee A, Chandrasekaran N. Antibacterial microemulsion prevents sepsis and triggers healing of wound in wistar rats. Colloids Surfaces B Biointerfaces [Internet]. Elsevier B.V.; 2013;105:152–7. Available from: https://doi.org/10.1016/j.colsurfb.2013.01.009

  76. Ryu KA, Park PJ, Kim SB, Bin BH, Jang DJ, Kim ST. Topical delivery of coenzyme Q10-loaded microemulsion for skin regeneration. Pharmaceutics. 2020;12:332.

    Article  CAS  PubMed Central  Google Scholar 

  77. Nastiti CMRR, Ponto T, Abd E, Grice JE, Benson HAE, Roberts MS. Topical nano and microemulsions for skin delivery. Pharmaceutics. 2017;9:1–25.

    Article  CAS  Google Scholar 

  78. Wang P, Huang B, Horng H, Yeh C. ScienceDirect wound healing. J Chinese Med Assoc [Internet]. 2018;81:94–101. Available from: https://doi.org/10.1016/j.jcma.2017.11.002

  79. Edmondson M, Newall N, Carville K, Smith J, Riley TV, Carson CF. Uncontrolled, open-label, pilot study of tea tree (Melaleuca alternifolia) oil solution in the decolonisation of methicillin-resistant Staphylococcus aureus positive wounds and its influence on wound healing. Int Wound J. 2011;8:375–84.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Santos EJF, Silva MANCGMM. Treatment of colonized/infected wounds using polyhexanide. Rev Enf Ref. 2011;3:135–42.

    Article  Google Scholar 

  81. Sienkiewicz M, Głowacka A, Poznańska-Kurowska K, Kaszuba A, Urbaniak A, Kowalczyk E. The effect of clary sage oil on staphylococci responsible for wound infections. Adv Dermatol Allergol. 2015;32:21–6.

    Article  Google Scholar 

  82. Meng N, Zhou NL, Zhang SQ, Shen J. Controlled release and antibacterial activity chlorhexidine acetate (CA) intercalated in montmorillonite. Int J Pharm. 2009;382:45–9.

    Article  CAS  PubMed  Google Scholar 

  83. Gong CY, Wu QJ, Wang YJ, Zhang DD, Luo F, Zhao X, et al. A biodegradable hydrogel system containing curcumin encapsulated in micelles for cutaneous wound healing. Biomaterials. 2013;34:6377–87.

    Article  CAS  PubMed  Google Scholar 

  84. Schäfer M, Werner S. Oxidative stress in normal and impaired wound repair. Pharmacol Res. 2008;58:165–71.

    Article  CAS  PubMed  Google Scholar 

  85. Khezri K, Farahpour MR, Mounesi RS. Efficacy of Mentha pulegium essential oil encapsulated into nanostructured lipid carriers as an in vitro antibacterial and infected wound healing agent. Colloids Surf A Physicochem Eng Asp. 2020;589:124414.

    Article  CAS  Google Scholar 

  86. Koca U, Süntar IP, Keles H, Yesilada E, Akkol EK. In vivo anti-inflammatory and wound healing activities of Centaurea iberica Trev. ex Spreng. J Ethnopharmacol. 2009;126:551–6.

    Article  PubMed  Google Scholar 

  87. Süntar IP, Akkol EK, Yilmazer D, Baykal T, Kirmizibekmez H, Alper M, et al. Investigations on the in vivo wound healing potential of Hypericum perforatum L. J Ethnopharmacol. 2010;127:468–77.

    Article  CAS  PubMed  Google Scholar 

  88. Labib RM, Ayoub IM, Michel HE, Mehanny M, Kamil V, Hany M, et al. Appraisal on the wound healing potential of Melaleuca alternifolia and Rosmarinus officinalis L. Essential oil-loaded chitosan topical preparations. PLoS One. 2019;14:1–17.

    Article  CAS  Google Scholar 

  89. Han X, Parker TL. Melaleuca (Melaleuca alternifolia) essential oil demonstrates tissue-remodeling and metabolism-modulating activities in human skin cells. Cogent Biol. 2017;3:1–7.

    CAS  Google Scholar 

  90. Lam NSK, Long XX, Griffin RC, Chen MK, Doery JCG. Can the tea tree oil (Australian native plant: Melaleuca alternifolia Cheel) be an alternative treatment for human demodicosis on skin? Parasitology. 2018;145:1510–20.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank the Laboratório de Avaliação e Desenvolvimento de Biomateriais do Nordeste (CERTBIO-UEPB/UFCG) for providing the infrastructure and carrying out the DSC and rheology analysis. Finally, the Analytical Center of the Federal University of Paraíba (NUCAL-UFPB) for its availability and assistance in the development, validation, and application of the dosing method.

Funding

This study was financed by the Coordination for the Improvement of Higher Education Personnel—Brazil (CAPES)—Finance Code 001. As well as the support of the State University of Paraíba (UEPB).

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Authors and Affiliations

  1. Graduate Program of Pharmaceutical Sciences, State University of Paraíba, Campina Grande, Paraiba, Brazil

    Karoll Moangella Andrade de Assis, Joandra Maísa da Silva Leite, Demis Ferreira de Melo, Malu Maria Lucas dos Reis, Vandiara Martins Moreira, João Walter de Souza da Silveira, Fátima Aparecida Castriani Sanches & Bolívar Ponciano Goulart de Lima Damasceno

  2. Laboratory of Development and Characterization of Pharmaceutical Products, Department of Pharmacy, State University of Paraíba (UEPB), Campina Grande, Paraiba, Brazil

    Karoll Moangella Andrade de Assis, Joandra Maísa da Silva Leite, Demis Ferreira de Melo, Joyce Cordeiro Borges, Lucas Matheus Barreto Santana, Malu Maria Lucas dos Reis, Vandiara Martins Moreira, João Walter de Souza da Silveira & Bolívar Ponciano Goulart de Lima Damasceno

  3. Laboratory of Microbiology, Department of Pharmacy, State University of Paraíba (UEPB), Campina Grande, Paraiba, Brazil

    Wilma Rainny Vieira da Rocha & Raïssa Mayer Ramalho Catão

  4. Research Institute for Drugs and Medicines, Federal University of Paraíba, João Pessoa, Paraíba, Brazil

    Sócrates Golzio dos Santos

  5. Medical Sciences Faculty, University Center UniFacisa, Campina Grande, Paraíba, Brazil

    Alyne da Silva Portela, Samantha Mayara de Sousa Silva & Tharcia Kiara Beserra de Oliveira

  6. Department of Dentistry, State University of Paraíba, Campina Grande, Paraíba, Brazil

    Emanuene Galdino Pires & Cassiano Francisco Weege Nonaka

  7. Federal Institute of Education, Science and Technology Baiano, IFBA, Campus Catu, Catu, Bahia, Brazil

    Fátima Aparecida Castriani Sanches

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  1. Karoll Moangella Andrade de Assis
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  15. Emanuene Galdino Pires
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  16. Cassiano Francisco Weege Nonaka
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  17. Fátima Aparecida Castriani Sanches
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  18. Bolívar Ponciano Goulart de Lima Damasceno
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Correspondence to Bolívar Ponciano Goulart de Lima Damasceno.

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The authors declare that they have no conflict of interest.

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All institutional and national guidelines for the care and use of laboratory animals were followed. The protocols were approved by the ethics committee on the use of animals at the Faculty of Medical Sciences of Campina Grande/PB (FCM/CESED) under protocol number 00730070082017.

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de Assis, K.M.A., da Silva Leite, J.M., de Melo, D.F. et al. Bicontinuous microemulsions containing Melaleuca alternifolia essential oil as a therapeutic agent for cutaneous wound healing. Drug Deliv. and Transl. Res. 10, 1748–1763 (2020). https://doi.org/10.1007/s13346-020-00850-0

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