Nergiz Gürbüz Çolak1, Emel Öykü Çetin Uyanikgil2, Yusuf Özbel3, Seray Töz4. 1. Department of Molecular Biology and Genetics, Izmir İnstitute of Technology, Urla, Izmir, Turkey. 2. Faculty of Pharmacy, Department of Pharmaceutical Technology, Ege University, Bornova, Izmir, Turkey. 3. Faculty of Medicine, Department of Parasitology, Ege University, Bornova, Izmir, Turkey. 4. Faculty of Medicine, Department of Parasitology, Ege University, Bornova, Izmir, Turkey. seray.ozensoy.toz@ege.edu.tr.
Abstract
PURPOSE: Leishmaniasis is a disease caused by different Leishmania spp., which are transmitted to humans by a bite of infected female sand flies. Cutaneous leishmaniasis (CL, oriental sore), visceral leishmaniasis (VL), and mucocutaneous leishmaniasis (MCL) are three main clinical forms, however, only CL and VL are seen in Turkey. Cutaneous leishmaniasis is characterized by skin lesion(s) and is one of the most important vector-borne diseases in Turkey with over 2000 cases reported annually in 40 out of 81 provinces. The treatment is usually made invasively and painfully by intralesional injection of pentavalent antimony compounds. Non-invasive and innovative treatment methods are needed as aimed in this study. METHODS: In the present study, one of the classical antileishmanial drugs, amphotericin B (AmB), encapsulated in liposomes was evaluated using non-invasive design based on chitosan, which is a nontoxic, biocompatible and biodegradable polymer. To avoid the invasive effect of conventional intralesional needle application, the drug was encapsulated in liposomes and incorporated into a chitosan gel for applying topically on the skin lesion. The efficacy of encapsulation of amphotericin B into liposomes and the drug release from liposomes were studied. The chitosan gel was evaluated for viscosity, flowability, appearance and pH. The efficacy of the drug embedded into chitosan gel, liposomal AmB alone and chitosan gel alone in four different concentrations was also tested using Leishmania spp. promastigotes in vitro. RESULTS: The findings have shown that AmB was encapsulated into the liposomes with high efficiency (86.6%) and long-term physical and chemical stability. Therefore, designed liposomal formulation was suitable for sustained release. The appearance of the drug-embedded chitosan gel was transparent and appropriate. Chitosan gels showed non- Newtonian behavior and plastic flow. The liposomal AmB also showed higher efficacy with no parasites in all concentrations while drug embedded into chitosan gel and chitosan gel alone were effective in two higher concentrations. The lower efficacy of the drug-embedded chitosan gel in 24 h in in-vitro study was probably due to slow release of the drug. CONCLUSION: The gel design created in this study will provide ease of use for the lesions of CL patients that do not have a specific number, size, and shape. Follow-up studies by the ex-vivo macrophage infection model with Leishmania intracellular amastigote forms and Leishmania-infected animal models are needed to understand the present design's efficacy better.
PURPOSE: Leishmaniasis is a disease caused by different Leishmania spp., which are transmitted to humans by a bite of infected female sand flies. Cutaneous leishmaniasis (CL, oriental sore), visceral leishmaniasis (VL), and mucocutaneous leishmaniasis (MCL) are three main clinical forms, however, only CL and VL are seen in Turkey. Cutaneous leishmaniasis is characterized by skin lesion(s) and is one of the most important vector-borne diseases in Turkey with over 2000 cases reported annually in 40 out of 81 provinces. The treatment is usually made invasively and painfully by intralesional injection of pentavalent antimony compounds. Non-invasive and innovative treatment methods are needed as aimed in this study. METHODS: In the present study, one of the classical antileishmanial drugs, amphotericin B (AmB), encapsulated in liposomes was evaluated using non-invasive design based on chitosan, which is a nontoxic, biocompatible and biodegradable polymer. To avoid the invasive effect of conventional intralesional needle application, the drug was encapsulated in liposomes and incorporated into a chitosan gel for applying topically on the skin lesion. The efficacy of encapsulation of amphotericin B into liposomes and the drug release from liposomes were studied. The chitosan gel was evaluated for viscosity, flowability, appearance and pH. The efficacy of the drug embedded into chitosan gel, liposomal AmB alone and chitosan gel alone in four different concentrations was also tested using Leishmania spp. promastigotes in vitro. RESULTS: The findings have shown that AmB was encapsulated into the liposomes with high efficiency (86.6%) and long-term physical and chemical stability. Therefore, designed liposomal formulation was suitable for sustained release. The appearance of the drug-embedded chitosan gel was transparent and appropriate. Chitosan gels showed non- Newtonian behavior and plastic flow. The liposomal AmB also showed higher efficacy with no parasites in all concentrations while drug embedded into chitosan gel and chitosan gel alone were effective in two higher concentrations. The lower efficacy of the drug-embedded chitosan gel in 24 h in in-vitro study was probably due to slow release of the drug. CONCLUSION: The gel design created in this study will provide ease of use for the lesions of CL patients that do not have a specific number, size, and shape. Follow-up studies by the ex-vivo macrophage infection model with Leishmania intracellular amastigote forms and Leishmania-infected animal models are needed to understand the present design's efficacy better.
Authors: Sophia Malli; Sebastien Pomel; Yasmine Ayadi; Claudine Deloménie; Antonio Da Costa; Philippe M Loiseau; Kawthar Bouchemal Journal: ACS Appl Bio Mater Date: 2019-05-22
Authors: Tatiana G Ribeiro; Miguel A Chávez-Fumagalli; Diogo G Valadares; Juçara R França; Lívia B Rodrigues; Mariana C Duarte; Paula S Lage; Pedro H R Andrade; Daniela P Lage; Leonardo V Arruda; Daniel R Abánades; Lourena E Costa; Vivian T Martins; Carlos A P Tavares; Rachel O Castilho; Eduardo A F Coelho; André A G Faraco Journal: Int J Nanomedicine Date: 2014-02-14