ABSTRACT
Based on the efficacy of paromomycin ointment and recent ongoing clinical trials of combination of paromomycin and gentamicin, a new physical form of films of the paromomycin and gentamicin was prepared and anti-Leishmania activities of the prepared films were assessed in vitro and in vivo. Paromomycin 15% and gentamicin 0.5% was incorporated in a film using ethyl cellulose and HPMC [Hydroxyl Propyl Methyl Cellulose]. In order to assess the drug release and anti-Leishmania activities of the preparation, a clone L. major parasite was established using a set of modified NNN medium without overaly liquid layer. Therapeutic effects of the films were evaluated using Balb/c mice model. The mice were inoculated with 2x10[6] L. major promastigotes [MRHO/IR/75/ER] and then when the lesions developed the mice were randomly divided in 3 groups, 10 mice per group, and treated with either perpetrated films or placebo for 28 days or left untreated. Growth inhibition of cloned promastigotes showed that the films have enough releasing capacity and in vivo system, the films containing paromomycin and gentamicin was able to reduce the lesion size and induced complete cure in 80% of the mice but relapse was seen in 60% of the cured mice and overall 50% cure rate was seen during 20 weeks period of the study. It seems that the prepared films might be further used in human clinical trials
ABSTRACT
In this study the level of IL-23 and IL-27 produced by macrophages derived from peripheral blood mononuclear cell culture collected from patients with healing or non-healing form of cutaneous leishmaniasis lesion were compared before and after treatment with live Leishmania to explore whether IL-23 or IL-27 plays any role in healing process of cutaneous lesions induced by L. major. Twenty patients resident in Isfahan Province, with healing or non-healing form of cutaneous leishmaniasis lesion caused by Leishmania major participated in this study. In vitro productions of IL-23 and IL-27 by peripheral blood derived macrophages, before and after stimulation with live L. major [MRHO/IR/75/ER] promastigotes were evaluated using ELISA method. Patient with healing form of lesion received no treatment and patient with non-healing form of lesion received at least 2 courses of glucantime. The mean production of IL-23 and IL-27 from macrophages of patients with healing form of lesion was significantly higher than patients with non-healing form of lesion. The levels of IL-23 and IL-27 in culture supernatants before and after stimulation in healing form of CL was significantly higher than non- healing form of CL [P < 0.001]. IL-23 and IL-27 might play a role in human leishmaniasis and further studies are needed to understand the role of IL-23 and IL-27 in leishmaniasis
ABSTRACT
Leishmaniosis is a complex disease, with a wide spectrum of clinical manifestation affects over 12 million people globally. Cutaneous leishmaniosis is still an important public health problem in many parts of the world, especially the Middle East. In spite of various forms of local treatment none is generally suitable for all forms of the disease in all. In this reseal-cli, therapeutic effects of paromomycin sulfate in combination with gentamicine sulfate films on cutaneous leishmaniosis in Balb/c mice has been studied. According to data and experiments available in Iran and some endemic countries about treatment of the disease by paromomycin, a new physical form of the drug was designed [drug film] and parasiticidal effects were evaluated in mice model. The base of the fi111is, ethyl cellulose and HPMC [hydroxy propyl Methyl Cellulose] contained paromomyein 15% and gentamicine 0.5%. In this regard female Balb/c mice were infected with 2X l0-6 L. major promastigotes [MRHO/IR/75/ER]. The mice were divided in three groups, of ten mice each. The placebo and test groups were received prepared placebo and drug films respectively. The remaining group, control received no treatment. The results indicated that utilization of this physical form of the drug in a mentioned period of time caused significant cure effects in the test group, so that 80% of Balb/c mice were cured at the end of the treatment period and there was no sign of cure in placebo and control groups. In general and because of good characters of the drug films and related results in animals, it is possible to use the new form of the drug in a human trial