Evaluation of an Electrospun Fiber Loaded with Ozonated Oil for the Treat¬ment of Leishmaniasis Lesions in an Experimental Model
-
Daniela Patrícia Tres
,
Carla Diel Fabrini
,
Janaina Fatima da Roza Cunha
,
Juliana Jurumenha Barreto
,
Mariana Pastri
,
Thaís Kaori Katsumata
,
Gabriel Nardi Fraga
,
Thaís Soprani Ayala
,
Douglas Cardoso Dragunski
,
Rafael Andrade Menolli
Abstract
Background: Cutaneous leishmaniasis (CL) is a neglected disease whose lesions may cause severe scarring and psy-chosocial impact. Current treatments often face poor patient adherence due to side effects and dosing. Electrospinning enables the incorporation of low-cost, bioactive compounds. Ozonated sunflower oil has shown potential to accelerate wound healing. This study aimed to evaluate electrospun fibers containing ozonated sunflower oil combined with standard anti-Leishmania therapy in lesions caused by Leishmania amazonensis in an animal model.
Methods: BALB/c mice (n=5/group) were infected with L. amazonensis (MHOM/BR/1977/LTB0016). Treatments in-cluded: meglumine antimoniate alone (MA), MA plus electrospun fiber with ozonated sunflower oil (MOO), MA plus fiber with non-ozonated sunflower oil (MNO) and an untreated control (CTRL). After 30 days, lesion size, parasite load, histology and systemic/local immune parameters were evaluated.
Results: All the groups exhibited lesion growth (MA 12±0.8%, MOO 24±0.4%, MNO 30±0.8 and CTRL 34±0.9%), but the MA group exhibited less growth. However, in the culture of the paws after the treatment, only in the MOO group, promastigotes did not grow, while the other groups reached titers of 1/6 (MA), 1/192 (MNO) and 1/384 (CTRL). Macroscopically, the MA and MOO groups showed complete healing of the lesion. Histologically, the MA group had a thicker epidermis (p<0.05) and the MA and MOO groups presented the lowest amount of cellular infiltration.
Conclusion: Treatment of cutaneous leishmaniasis lesions in a mouse model with an electrospun fiber containing ozonated oil improved drug treatment, ameliorating lesions and could be explored as an alternative treatment for this parasitic disease.
1. Steverding D (2017) The history of leish-maniasis. Parasit Vectors. 10(1): 1–10.
2. PAHO-PanAmerican Health Organization (2018) Leishmaniasis: Epidemiological Re¬port of the Americas. PAHO/WHO In¬stitutional Repository.
3. Bennis I, De Brouwere V, Belrhiti Z, Sa¬hibi H, Boelaert M (2018) Psychosocial burden of localised cutaneous Leish¬man-iasis: A scoping review. BMC Pub¬lic Health. 18(1): 1–12.
4. Barba PJ, Morgado-Carrasco D, Quera A (2022) Tratamiento de leishmaniasis cutánea infantil con miltefosina. Actas Dermo¬si¬filiogr. 113(8): 827–831.
5. Iranpour S, Hosseinzadeh A, Alipour A (2019) Efficacy of miltefosine compared with glu¬cantime for the treatment of cu-tane¬ous leishmaniasis: a systematic re-view and meta-analysis. Epidemiol Health. 41: e2019011.
6. Castro MDM, Rode J, Machado PRL, Llanos-Cuentas A, Hueb M, Cota G, Rojas IV, Orobio Y, Sarmiento OO, Rojas E, Quintero J, Pimentel MIF, Soto J, Suprien C, Al-varez F, Ramos AP, Arantes RBS, da Silva RE, Arenas CM, Vélez ID, Lyra MR, Saravia NG, Arana B, Alexander N (2023) Cutaneous leishmaniasis treat¬ment and therapeutic outcomes in special pop¬ulations: A col-laborative retrospective study. PLoS Negl Trop Dis. 17(1): e0011029.
7. Pivotto AP, Banhuk FW, Staffen IV, Daga MA, Ayala TS, Menolli RA (2020) Clin-ical Uses and Molecular Aspects of Ozone Therapy: A Review. Online J Bi¬ol Sci. 20(1): 37–49.
8. Néri J dos SV, Lomba E, Karam AM, Reis SR de A, Marchionni AMT, Medrado ARAP (2017) Ozone therapy influence in the tissue repair process: A literature review. J Oral Diagn. 2: 1–6.
9. Lim Y, Lee H, Woodby B, Valacchi G (2019) Ozonated oils and cutaneous wound heal¬ing. Curr Pharm Des. 25(20): 2264–2278.
10. Xue J, Xie J, Liu W, Xia Y (2017) Elec-trospun nanofibers: new concepts, mate-rials and applications. Acc Chem Res. 50(8): 1976–1987.
11. Miguel SP, Figueira DR, Simões D, Ribei-ro MP, Coutinho P, Ferreira P, Correia IJ (2018) Electrospun polymeric nano¬fibres as wound dressings: A review. Colloids Surf B Biointerfaces. 169: 60–71.
12. Fabrini CD, Ayala TS, Menolli RA (2024) Electrospun polymers in cutaneous wound healing and delivery systems-a review. Int J Polym Mater Polym Bio-mater. 74 (12): 1157–1167.
13. Moureu S, Violleau F, Ali Haimoud-Lek-hal D, Calmon A (2015) Ozonation of sunflower oils: Impact of experi¬mental conditions on the composition and the an¬tibacterial activity of ozonized oils. Chem Phys Lipids. 186: 79–85.
14. Martinez Tellez G, Ledea Lozano O, Díaz Gómez MF (2006) Measurement of Per-oxidic Species in Ozonized Sunflower Oil. Ozone Sci Eng. 28(3): 181–185.
15. Skalska K, Ledakowicz S, Perkowski J, Sen¬cio B (2009) Germicidal properties of ozo¬nated sunflower oil. Ozone Sci Eng. 31 (3): 232–237.
16. Green LC, Wagner DA, Glogowski J, Skip¬per PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite and [15N] nitrate in biological fluids. Anal Bioch. 126(1): 131–138.
17. Chen S, Liu B, Carlson MA, Gombart AF, Reilly DA, Xie J (2017) Recent advanc-es in electrospun nanofibers for wound heal¬ing. Nanomedicine. 12(11): 1335–1352.
18. Costa RGFF, De Oliveira JE, De Paula GF, De Picciani PHS, De Medeiros ES, Ri¬beiro C, Mattoso LHC (2012) Elec¬tro-spin¬ning of Polymers in Solution. Part I: Theoretical Foundation. Polímer¬os 22 (2): 170–177.
19. Moura LM de, Santos KLM, Passos JAR dos, Silva GF de V, Neres CA da S, Cas¬tro WPD de, Santos LGS, Silva DGR (2025) Application of electrospun nano¬fibers in the treatment of leishmaniasis: a mini-review. Contr L Cienc Socia. 18 (5): e17776.
20. Mohebali F, Aghabarari B, Vaezi MR, Zarei Z, Hassanpour G, Alizadeh Z, Latifi A, Mohebali M (2025) Biom-acromolecule chitosan carrying meglu-mine antimoni¬ate coated on a sil-ver/polyurethane nano¬composite as a wound dressing: Ther¬a¬peutic efficacy on cutaneous leishmania¬sis caused by Leishmania major in BALB/ c mice. Int J Biol Macromol. 1: 307.
21. Hu X, Liu S, Zhou G, Huang Y, Xie Z, Jing X (2014) Electrospinning of poly-meric nanofibers for drug delivery ap-plica¬tions. J Control Release. 185(1): 12–21.
22. Orlandin JR, Machado LC, Ambrósio CE, Travagli V (2021) Ozone and its deriva-tives in veterinary medicine: A careful appraisal. Vet Anim Sci. 13: 100191.
23. Valacchi G, Fortino V, Bocci V (2005) The dual action of ozone on the skin. Br J Dermatol. 153(6): 1096–1100.
24. Valacchi G, Lim Y, Belmonte G, Miracco C, Zanardi I, Bocci V, Travagli V (2011) Ozonated sesame oil enhances cutane¬ous wound healing in SKH1 mice. Wound Re¬pair Regen. 19(1): 107–115.
25. Rajasekaran R, Chen YPP (2015) Poten¬tial therapeutic targets and the role of tech-nology in developing novel an¬tileishma-nial drugs. Drug Discov Today. 20(8): 958–968.
26. Noronha LPT, Martins MDA, Castro-Jun-ior AB, Thorstenberg ML, Costa-Soares L, Rangel TP, Carvalho-Gondim F, Rossi-Bergmann B, Savio LEB, Can¬etti CCA, Coutinho-Silva R (2023) Cys-teinyl-leu¬ko¬trienes promote cutaneous Leish¬man¬iasis control. Front Cell Infect Microbi¬ol. 13: 1192800.
27. Scott P, Novais FO (2016) Cutaneous leish¬maniasis: immune responses in pro-tec¬tion and pathogenesis. Nat Rev Im-mu¬nol. 16(9): 581–592.
28. Firdous R, Yasinzai M, Ranja K (2009) Ef-ficacy of Glucantime in the treatment of Old World cutaneous leishmaniasis. Int J Dermatol. 48(7): 758–762.
29. Oliveira AGL, Brito PD, Schubach AO, Oliveira RVC, Saheki MN, Lyra MR, Salgueiro MM, Terceiro BF, Pimentel MIF, Vasconcellos EC, Vlete-Rosalino CM (2013) Influence of the nutritional status in the clinical and therapeutical evolution in adults and elderly with American tegumentary leishmaniasis. Acta Trop. 128(1): 36–40.
30. Espir TT, Guerreiro TS, Naiff MF, Figuei¬ra LP, Soares FV, da Silva SS, Franco AMR (2016) Evaluation of different di-agnostic methods of American Cutane-ous Leishmaniasis in the Brazilian Ama-zon. Exp Parasitol. 167: 1–6.
31. Pivotto AP, de Souza Lima LB, Michelon A, Ferreira CZP, Gandra RF, Ayala TS, Menolli RA (2024) Topical application of ozonated sunflower oil accelerates the healing of lesions of cutaneous leish¬man-iasis in mice under meglumine an¬timoni-ate treatment. Med Microbiol Immunol. 213(1): 4.
32. Sanguanini RC, Bento MF, de Oliveira E, Arnhold E, Faleiro MBR, Franco LG, Matos MPC, Moura VMBD (2020) Ozo¬nized solutions favor the repair of ex¬per¬imentally induced skin wounds in rats. Pesquisa Veterinaria Brasileira. 40(11): 914–921.
33. Eming SA, Martin P, Tomic-Canic M (2014) Wound repair and regeneration: Mecha¬nisms, signaling and translation. Sci Transl Med. 6(265): 1–36.
34. Sandoval Pacheco CM, Araujo Flores GV, Gonzalez K, Castro Gomes CM, Passero LFD, Tomokane TY, Sosa-Ochoa W, Zún¬iga C, Calzada J, Saldaña A, Corbett CEP, Silveira FT, Laurenti MD (2021) Macro¬phage polarization in the skin le-sion caused by Neotropical species of Leishmania sp. J Immunol Res. 2021: 5596876.
35. Cabral IL, Utzig SL, Banhuk FW, Staffen IV, Loth EA, de Amorim JPA, Negretti F, Gandra RF, Ayala TS, Menolli RA (2020) Aqueous ozone therapy improves the stand¬ard treatment of leishmaniasis lesions in animals leading to local and systemic al¬terations. Parasitol Res. 119(12): 4243–4253.
36. Nakamura AM, Costa MC da, Gómez JLÁ, Paiva FN de, Nardi ABD (2023) Reparação do retalho axial dorsal em ra-tos tratados com óleo ozonizado. Med Vet (UFRPE) [Internet]. 17(1): 37–45.
37. Silva MLA, Lauz S, Silva VD, Araujo AMW, Silva MDA, Tatekawa LA, Danielski TP (2013) Evaluation of topic linoleic acid application on random-pattern skin flaps in rats. Braz J Plast Surg. 28(4): 643–650.
38. Sagai M, Bocci V (2011) Mechanisms of action involved in ozone therapy: Is heal¬ing induced via a mild oxidative stress? Med Gas Res. 1(1): 1–18.
2. PAHO-PanAmerican Health Organization (2018) Leishmaniasis: Epidemiological Re¬port of the Americas. PAHO/WHO In¬stitutional Repository.
3. Bennis I, De Brouwere V, Belrhiti Z, Sa¬hibi H, Boelaert M (2018) Psychosocial burden of localised cutaneous Leish¬man-iasis: A scoping review. BMC Pub¬lic Health. 18(1): 1–12.
4. Barba PJ, Morgado-Carrasco D, Quera A (2022) Tratamiento de leishmaniasis cutánea infantil con miltefosina. Actas Dermo¬si¬filiogr. 113(8): 827–831.
5. Iranpour S, Hosseinzadeh A, Alipour A (2019) Efficacy of miltefosine compared with glu¬cantime for the treatment of cu-tane¬ous leishmaniasis: a systematic re-view and meta-analysis. Epidemiol Health. 41: e2019011.
6. Castro MDM, Rode J, Machado PRL, Llanos-Cuentas A, Hueb M, Cota G, Rojas IV, Orobio Y, Sarmiento OO, Rojas E, Quintero J, Pimentel MIF, Soto J, Suprien C, Al-varez F, Ramos AP, Arantes RBS, da Silva RE, Arenas CM, Vélez ID, Lyra MR, Saravia NG, Arana B, Alexander N (2023) Cutaneous leishmaniasis treat¬ment and therapeutic outcomes in special pop¬ulations: A col-laborative retrospective study. PLoS Negl Trop Dis. 17(1): e0011029.
7. Pivotto AP, Banhuk FW, Staffen IV, Daga MA, Ayala TS, Menolli RA (2020) Clin-ical Uses and Molecular Aspects of Ozone Therapy: A Review. Online J Bi¬ol Sci. 20(1): 37–49.
8. Néri J dos SV, Lomba E, Karam AM, Reis SR de A, Marchionni AMT, Medrado ARAP (2017) Ozone therapy influence in the tissue repair process: A literature review. J Oral Diagn. 2: 1–6.
9. Lim Y, Lee H, Woodby B, Valacchi G (2019) Ozonated oils and cutaneous wound heal¬ing. Curr Pharm Des. 25(20): 2264–2278.
10. Xue J, Xie J, Liu W, Xia Y (2017) Elec-trospun nanofibers: new concepts, mate-rials and applications. Acc Chem Res. 50(8): 1976–1987.
11. Miguel SP, Figueira DR, Simões D, Ribei-ro MP, Coutinho P, Ferreira P, Correia IJ (2018) Electrospun polymeric nano¬fibres as wound dressings: A review. Colloids Surf B Biointerfaces. 169: 60–71.
12. Fabrini CD, Ayala TS, Menolli RA (2024) Electrospun polymers in cutaneous wound healing and delivery systems-a review. Int J Polym Mater Polym Bio-mater. 74 (12): 1157–1167.
13. Moureu S, Violleau F, Ali Haimoud-Lek-hal D, Calmon A (2015) Ozonation of sunflower oils: Impact of experi¬mental conditions on the composition and the an¬tibacterial activity of ozonized oils. Chem Phys Lipids. 186: 79–85.
14. Martinez Tellez G, Ledea Lozano O, Díaz Gómez MF (2006) Measurement of Per-oxidic Species in Ozonized Sunflower Oil. Ozone Sci Eng. 28(3): 181–185.
15. Skalska K, Ledakowicz S, Perkowski J, Sen¬cio B (2009) Germicidal properties of ozo¬nated sunflower oil. Ozone Sci Eng. 31 (3): 232–237.
16. Green LC, Wagner DA, Glogowski J, Skip¬per PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite and [15N] nitrate in biological fluids. Anal Bioch. 126(1): 131–138.
17. Chen S, Liu B, Carlson MA, Gombart AF, Reilly DA, Xie J (2017) Recent advanc-es in electrospun nanofibers for wound heal¬ing. Nanomedicine. 12(11): 1335–1352.
18. Costa RGFF, De Oliveira JE, De Paula GF, De Picciani PHS, De Medeiros ES, Ri¬beiro C, Mattoso LHC (2012) Elec¬tro-spin¬ning of Polymers in Solution. Part I: Theoretical Foundation. Polímer¬os 22 (2): 170–177.
19. Moura LM de, Santos KLM, Passos JAR dos, Silva GF de V, Neres CA da S, Cas¬tro WPD de, Santos LGS, Silva DGR (2025) Application of electrospun nano¬fibers in the treatment of leishmaniasis: a mini-review. Contr L Cienc Socia. 18 (5): e17776.
20. Mohebali F, Aghabarari B, Vaezi MR, Zarei Z, Hassanpour G, Alizadeh Z, Latifi A, Mohebali M (2025) Biom-acromolecule chitosan carrying meglu-mine antimoni¬ate coated on a sil-ver/polyurethane nano¬composite as a wound dressing: Ther¬a¬peutic efficacy on cutaneous leishmania¬sis caused by Leishmania major in BALB/ c mice. Int J Biol Macromol. 1: 307.
21. Hu X, Liu S, Zhou G, Huang Y, Xie Z, Jing X (2014) Electrospinning of poly-meric nanofibers for drug delivery ap-plica¬tions. J Control Release. 185(1): 12–21.
22. Orlandin JR, Machado LC, Ambrósio CE, Travagli V (2021) Ozone and its deriva-tives in veterinary medicine: A careful appraisal. Vet Anim Sci. 13: 100191.
23. Valacchi G, Fortino V, Bocci V (2005) The dual action of ozone on the skin. Br J Dermatol. 153(6): 1096–1100.
24. Valacchi G, Lim Y, Belmonte G, Miracco C, Zanardi I, Bocci V, Travagli V (2011) Ozonated sesame oil enhances cutane¬ous wound healing in SKH1 mice. Wound Re¬pair Regen. 19(1): 107–115.
25. Rajasekaran R, Chen YPP (2015) Poten¬tial therapeutic targets and the role of tech-nology in developing novel an¬tileishma-nial drugs. Drug Discov Today. 20(8): 958–968.
26. Noronha LPT, Martins MDA, Castro-Jun-ior AB, Thorstenberg ML, Costa-Soares L, Rangel TP, Carvalho-Gondim F, Rossi-Bergmann B, Savio LEB, Can¬etti CCA, Coutinho-Silva R (2023) Cys-teinyl-leu¬ko¬trienes promote cutaneous Leish¬man¬iasis control. Front Cell Infect Microbi¬ol. 13: 1192800.
27. Scott P, Novais FO (2016) Cutaneous leish¬maniasis: immune responses in pro-tec¬tion and pathogenesis. Nat Rev Im-mu¬nol. 16(9): 581–592.
28. Firdous R, Yasinzai M, Ranja K (2009) Ef-ficacy of Glucantime in the treatment of Old World cutaneous leishmaniasis. Int J Dermatol. 48(7): 758–762.
29. Oliveira AGL, Brito PD, Schubach AO, Oliveira RVC, Saheki MN, Lyra MR, Salgueiro MM, Terceiro BF, Pimentel MIF, Vasconcellos EC, Vlete-Rosalino CM (2013) Influence of the nutritional status in the clinical and therapeutical evolution in adults and elderly with American tegumentary leishmaniasis. Acta Trop. 128(1): 36–40.
30. Espir TT, Guerreiro TS, Naiff MF, Figuei¬ra LP, Soares FV, da Silva SS, Franco AMR (2016) Evaluation of different di-agnostic methods of American Cutane-ous Leishmaniasis in the Brazilian Ama-zon. Exp Parasitol. 167: 1–6.
31. Pivotto AP, de Souza Lima LB, Michelon A, Ferreira CZP, Gandra RF, Ayala TS, Menolli RA (2024) Topical application of ozonated sunflower oil accelerates the healing of lesions of cutaneous leish¬man-iasis in mice under meglumine an¬timoni-ate treatment. Med Microbiol Immunol. 213(1): 4.
32. Sanguanini RC, Bento MF, de Oliveira E, Arnhold E, Faleiro MBR, Franco LG, Matos MPC, Moura VMBD (2020) Ozo¬nized solutions favor the repair of ex¬per¬imentally induced skin wounds in rats. Pesquisa Veterinaria Brasileira. 40(11): 914–921.
33. Eming SA, Martin P, Tomic-Canic M (2014) Wound repair and regeneration: Mecha¬nisms, signaling and translation. Sci Transl Med. 6(265): 1–36.
34. Sandoval Pacheco CM, Araujo Flores GV, Gonzalez K, Castro Gomes CM, Passero LFD, Tomokane TY, Sosa-Ochoa W, Zún¬iga C, Calzada J, Saldaña A, Corbett CEP, Silveira FT, Laurenti MD (2021) Macro¬phage polarization in the skin le-sion caused by Neotropical species of Leishmania sp. J Immunol Res. 2021: 5596876.
35. Cabral IL, Utzig SL, Banhuk FW, Staffen IV, Loth EA, de Amorim JPA, Negretti F, Gandra RF, Ayala TS, Menolli RA (2020) Aqueous ozone therapy improves the stand¬ard treatment of leishmaniasis lesions in animals leading to local and systemic al¬terations. Parasitol Res. 119(12): 4243–4253.
36. Nakamura AM, Costa MC da, Gómez JLÁ, Paiva FN de, Nardi ABD (2023) Reparação do retalho axial dorsal em ra-tos tratados com óleo ozonizado. Med Vet (UFRPE) [Internet]. 17(1): 37–45.
37. Silva MLA, Lauz S, Silva VD, Araujo AMW, Silva MDA, Tatekawa LA, Danielski TP (2013) Evaluation of topic linoleic acid application on random-pattern skin flaps in rats. Braz J Plast Surg. 28(4): 643–650.
38. Sagai M, Bocci V (2011) Mechanisms of action involved in ozone therapy: Is heal¬ing induced via a mild oxidative stress? Med Gas Res. 1(1): 1–18.
| Files | ||
| Issue | Vol 19 No 4 (2025) | |
| Section | Original Article | |
| DOI | https://doi.org/10.18502/jad.v19i4.21211 | |
| Keywords | ||
| Electrospun fiber Cutaneous leishmaniasis Ozone therapy Wound healing BALB/c | ||
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How to Cite
1.
Tres D, Fabrini C, Cunha J, Jurumenha Barreto J, Pastri M, Katsumata T, Fraga G, Ayala T, Dragunski D, Menolli R. Evaluation of an Electrospun Fiber Loaded with Ozonated Oil for the Treat¬ment of Leishmaniasis Lesions in an Experimental Model. J Arthropod Borne Dis. 2026;19(4):329–342.
