Cutaneous/Mucocutaneous Leishmaniasis Treatment for Wound Healing: Classical versus New Treatment Approaches
Abstract
:1. Introduction
2. Cutaneous and Mucocutaneous Leishmaniasis
3. Classical Treatments
4. Topical Treatment Strategies
5. Semi-Solid Formulations
Type of Formulation | Drug | Production Method | Results | References |
---|---|---|---|---|
Polymeric nanoparticles | Meglumine antimoniate | Nanoemulsification | The formulation was able to control a leishmaniasis infection as the same level than the reference injected Glucantime®. | [46] |
Film-Forming (spray formulation) | Nitroimidazole DNDI-0690 | Dispersion in water/ethanol medium of polymer and plasticizer | The formulation reduced the parasites in the skin, but did not influence the lesion size compared with the control. | [47] |
Emulsions | (PEI25-CAN-γ-Fe2O3 NPs) Nano-Leish-IL | Emulsion | The elimination of infection by L. major in vivo assays was observed. | [48] |
Emulsion | Amphotericin B | Emulsion | Cure rates of 39.4% were observed, showing that topical Amphotericin B was not effective for the treatment of CL. | [49] |
Nanostructured lipid carriers (NLCs) incorporated into a hydrogel | Amphotericin B | NLC was produced by the emulsification method, polymer and plasticized was added and homogenized. | The formulation was around five times slower in the IC50 values in vivo assays. | [50] |
Nanotransfersomes incorporated in chitosan gel | Rifampicin | Film hydration method follow, chitosan added and homogenized | Nanotransfersomes were more effective compared to drug pristine. Furthermore, the nanotransfersomes incorporate in chitosan gel reduced the wound healing significantly. | [51] |
Membranes | Diethyl dithiocarbamate (DETC) | Bacterial cellulose membranes were obtained from cultivation of Gluconacetobacter hansenii | Reduction in significance of parasite load and of infection of L. braziliensis in macrophages | [52] |
Membranes | amphotericin B (AmB) | A polyvinyl alcohol, (PVA) hydrogel produced by casting | The leishmanicidal, antifungal, and cytotoxic activity of the system loaded with AmB were signaled an efficient pharmacological activity and adequate biocompatibility of PVA-AmB hydrogels with great potential in the topical treatment of CL. | [53] |
Self-nanoemulsifying drug delivery systems | buparvaquone (BPQ) | Dispersion of drug, oil, surfactant in solvent | Reduction of parasitism and indicated healing in animals | [54] |
Liposomes | Amphotericin B (AmB) | Film hydration method | Liposomal formulation was considerably higher than that observed for pristine AmB | [55] |
Liposomes | stibogluconate and ketoconazole | Film hydration method | In vitro and in vivo anti- indicated a 10.67-fold lower IC50 value | [56] |
Liposomes | Azithromycin and glucantine | dehydration–rehydration vesicle; (DRV) method dehydration–rehydration vesicle; (DRV) method Dehydratation-rehydratation vesicle method | In vivo assays showed a cure rate of 77% for azithromycin and 76% for glucantime. | [57] |
Liposomes | Amphotericin B | - | Liposomal formulation was stable and showed capacity to penetrate into the skin. It was also efficient against L. major in vitro and in vivo. | [58] |
Hydrogels | Miltefosine | Dispersion of drug and polymer in water. | The topical 0.5% miltefosine gel formulation was efficacious and non-toxic when administered topically in vivo assays. | [59] |
Hydrogels | Meglumine antimoniate | Polymer homogenization in aqueous medium | It showed high retention on the skin and reduction of IC50 compared the control. | [60] |
Hydrogels | Amphotericin B | Homogenization of polymer with constant mechanical stirring in aqueous medium | No cytotoxic effects were observed in macrophages. No in vitro and in vivo assays were done yet. | [61] |
Ointment | Ursolic acid | melting | Reducing the L. amazonensis infection, attribute to the occlusive effect of the ointment, which promoted ursolic acid permeability across the skin with a prolonged the drug delivery | [44] |
Ointment | (−)-α-bisabolol | Melting | In vivo assays prevented microbial infection and inflammation, leishmanial and healing properties. | [45] |
6. Films and Membranes
7. Nanomaterials
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Drug | Administration Route | Dose | Mechanism of Action | Side Effects | References |
---|---|---|---|---|---|
N-methylglucamine antimoniate | Intravenous, or intramuscular | CL: 15 mg/kg/day (20 days); ML: 20 mg/kg/day; | Two mechanisms: (i) it binds with ribonucleosides forming a complex, preventing topoisomerases from carrying out their function in the process of DNA replication and transcription; (ii) it increases pro-inflammatory cytokines in the host, enhancing the phagocytic action of neutrophils and monocytes. | Myalgia, liver changes, abdominal pain and cardiac disorders. | [28] |
Amphotericin B deoxycholate | Intravenous | CL and ML: 1 mg/kg/day; | It binds with the ergosterol of the pathogens’ plasma membrane. It will cause the dysfunction of the cells through forming of ion pore channels. The pore formation will cause inhibition of glycolysis and rapid efflux of K+ and Mg+ ions inside cells leading to an increase in acidity of these cells and cells death | Fever and chills at the moment of the infusion. Anemia, neutropenia, thrombocytopenia, and changes in liver enzymes. | [29,30,31] |
Amphotericin B | Intravenous | CL and ML: 1–4 mg/kg/day (daily); | It is the same as Amphotericin B deoxycholate, the difference happens with the addition of lipid formulations that help to decrease side effects and to reach only target tissues with maximum concentration and selectivity, serum concentration of the drug should be kept low. | Loss of potassium and magnesium, anaphylaxis, fevers. Anemia and nephrotoxicity | [29,31] |
Pentamidine isethionate | Intravenous or intramuscular | CL and ML: 4 mg/kg/day; | It interferes production of polyamine, RNA polymerase activity, causing the inhibition of protein and RNA synthesis. It has ability to enter the pathogen’s cell and bind the RNA transfer is carried out and thus block the synthesis of proteins, nucleic acids, phospholipids and folate. | Hypoglycemia, hypotension, arrhythmias, prolonged QT interval, fatigue, night sweats, anorexia, nausea, vomiting, syncope, rash, nephrotoxicity, hepatotoxicity. | [32] |
Miltefosine | Oral | CL and ML: 2.5 mg/kg/day. | It activates cytotoxic macrophages, the ability to interfere with cell signaling pathways, carry out modifications in the lipid membrane, as well as programmed cell death (apoptosis). When administering the drug, it will have the ability to interfere with the pathogen’s cell membrane, influence the lipid composition, permeability, and fluidity of the membrane, as well as the metabolism of phospholipids, causing apoptosis to be stimulated. | Anorexia, nausea, vomiting and diarrhea, skin allergy, high concentrations of liver transaminases and, in rarer cases, renal failure. | [33] |
Imiquimod | Topical | 5% | The off-label use of topical imiquimod has been evaluated as an agent in the treatment of several infectious diseases. In cutaneous leishmaniasis, it acts on the stimulation process, causing TCD4 lymphocytes to secrete interferon-y, activating the release of macrophages that will follow the infection site to phagocytose the amastigote forms of leishmania. | Some local side effects may occur in high dose situations, such as itching, erythema, burning, local irritation. | [34,35] |
Paromomycin | Topical and parenteral | It inhibits the synthesis of proteins present in the protozoan structure. It binds to the 30S ribosomal unit causing an accumulation of abnormal ribosomal complexes leading to the death of the protozoan. | Nephrotoxicity, ototoxicity and liver dysfunction | [21,36,37] | |
Azithromycin | Oral | 500 mg/day (20 days) | It is an antibacterial that works by preventing protein production and interfering with bacterial growth. Its antiparasitic action is possibly associated with its immunomodulatory activity preventing the production of cytokines and pro-inflammatory mediators. | nausea, vomiting and diarrhea | [38] |
Azoles | Oral | Ketoconazole: 200 to 400 mg/twice a day (for three months) Fluconazole: 5 to 8 mg/kg (for 4–12 weeks) Itraconazole: ML: 4 mg/kg/day (for 6 weeks) | Its mechanism of action is based on blocking the synthesis of ergosterol, an essential molecule for bioregulation and cell membrane integrity. | Itching, nausea, vomiting, allergic and anorexia | [21] |
Sodium Stibogluconate | Intravenous [or Intramuscular | 20 mg/kg/day (for 20 days) | Its mechanism of action is based on the inhibition of glycolysis and oxidation of fatty acids in protozoan cells. | Nausea, vomiting, abdominal pain, fatigue, muscle pain, arrhythmias, liver disorders. | [39] |
Zinc sulfate | Oral | 10 mg/kg/day | The effect of zinc sulfate shows relatively positive but variable results in the treatment of leishmaniasis. The evaluation of the effect of zinc sulphate in the treatment of leishmaniasis is still not well understood, the effect may be related to the action of zinc sulphate on protozoan enzymes interfering with DNA synthesis. | - | [40] |
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Severino, P.; Santana, W.; Lisboa, E.S.; Santos, V.L.S.d.; Lima, E.T.d.S.; Cardoso, J.C.; Albuquerque-Junior, R.L.C.d.; Naveros, B.C.; Santini, A.; Souto, E.B.; et al. Cutaneous/Mucocutaneous Leishmaniasis Treatment for Wound Healing: Classical versus New Treatment Approaches. Microbiol. Res. 2022, 13, 836-852. https://doi.org/10.3390/microbiolres13040059
Severino P, Santana W, Lisboa ES, Santos VLSd, Lima ETdS, Cardoso JC, Albuquerque-Junior RLCd, Naveros BC, Santini A, Souto EB, et al. Cutaneous/Mucocutaneous Leishmaniasis Treatment for Wound Healing: Classical versus New Treatment Approaches. Microbiology Research. 2022; 13(4):836-852. https://doi.org/10.3390/microbiolres13040059
Chicago/Turabian StyleSeverino, Patrícia, Wanessa Santana, Erika S. Lisboa, Victoria L. S. dos Santos, Erica T. dos Santos Lima, Juliana C. Cardoso, Ricardo L. C. de Albuquerque-Junior, Beatriz C. Naveros, Antonello Santini, Eliana B. Souto, and et al. 2022. "Cutaneous/Mucocutaneous Leishmaniasis Treatment for Wound Healing: Classical versus New Treatment Approaches" Microbiology Research 13, no. 4: 836-852. https://doi.org/10.3390/microbiolres13040059
APA StyleSeverino, P., Santana, W., Lisboa, E. S., Santos, V. L. S. d., Lima, E. T. d. S., Cardoso, J. C., Albuquerque-Junior, R. L. C. d., Naveros, B. C., Santini, A., Souto, E. B., & Jain, S. (2022). Cutaneous/Mucocutaneous Leishmaniasis Treatment for Wound Healing: Classical versus New Treatment Approaches. Microbiology Research, 13(4), 836-852. https://doi.org/10.3390/microbiolres13040059