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The aim of this study was to evaluate the antileishmanial effects of topical liposomal paromomycin sulfate (PM) in Leishmania major-infected BALB/c mice. Liposomes containing 10 or 15% PM (Lip-PM-10 and Lip-PM-15, respectively) were prepared by the fusion method and were characterized for their size and encapsulation efficiency. The penetration of PM from the liposomal PM formulations (LPMFs) through and into skin was evaluated in vitro with Franz diffusion cells fitted with mouse skin at 37°C for 8 h. The in vitro permeation data showed that almost 15% of the LPMFs applied penetrated the mouse skin, and the amount retained in the skin was about 60% for both formulations. The 50% effective doses of Lip-PM-10 and Lip-PM-15 against L. major promastigotes in culture were 65.32 and 59.73 g/ml, respectively, and those against L. major amastigotes in macrophages were 24.64 and 26.44 g/ml, respectively. Lip-PM-10 or Lip-PM-15 was used topically twice a day for 4 weeks to treat L. major lesions on BALB/c mice, and the results showed a significantly (P < 0.001) smaller lesion size in the mice in the treated groups than in the mice in the control group, which received either empty liposomes or phosphate-buffered saline (PBS). Eight weeks after the beginning of the treatment, every mouse treated with LPMFs was completely cured. The spleen parasite burden was significantly (P < 0.001) lower in mice treated with Lip-PM-10 or Lip-PM-15 than in mice treated with PBS or control liposomes, but no significant difference was seen between the two groups treated with either Lip-PM-10 or Lip-PM-15. The results suggest that topical liposomal PM may be useful for the treatment of cutaneous leishmaniasis.Leishmaniasis, which has diverse clinical manifestations, is caused by different species of Leishmania and is endemic in many countries (49). Although cutaneous leishmaniasis (CL) is a self-healing disease, healing takes a long time, and healing times of even up to 2 years have been reported (37). Pentavalent antimonials, which are still the first-line treatment for CL, require multiple injections and are painful; as such, they are not tolerated by most of the patients and, moreover, are not always effective. In addition, resistance to pentavalent antimonials has been reported (12,13,33).Paromomycin sulfate (PM) was reported to show anti-Leishmania activity in the 1960s, and since then PM showed promising activity against both CL and visceral leishmaniasis (VL) in clinical trials (13, 31). Recently, the parenteral formulation of PM has been approved for use for the treatment of VL (27). Nevertheless, the systemic use of PM might cause nephrotoxicity. The conventional topical dosage forms of PM have been tested in clinical trials for their activities against CL and showed promising results, but acceptable efficacy was not always seen (2,3,5,13,18,23,28,43). The formidable barrier nature of the stratum corneum (SC) of the skin does not allow the penetration of drugs with high hydrophilicities and molecular weights, like PM (19). Furthermo...

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Background: Hepatotoxicity due to drugs is the most common cause of deaths. Nephrotoxicity of the drugs is usually associated with the drugs accumulation in renal tissue. Paromomycin sulfate (PMS) is an anti-leishmania drug. Although the topical approach for the treatment of leishmania is attractive, its use might cause nephrotoxicity and hepatotoxicity. Objectives: This study aimed to evaluate probable nephrotoxicity and hepatotoxicity of topically administered PMS liposomes. Materials and Methods: Nine groups of male rats were used in this study; each group consisted of 6 rats that were evaluated in 3 time periods of 10, 20, and 30 days. Three groups were placed in each time period; a control group did not receive any medicine; a negative control group received liposome without paromomycin sulfate; and a positive control group received nanoliposomal formulations containing paromomycin sulfate. Pharmaceutical formulation (topical form) was used 2 times a day in a 12-hour interval. At the end of the period, hepatic enzymes (ALT, AST, and ALK), BUN levels, and serum creatinine were measured. Results:The results showed that no significant change was occurred in the amount of the above factors compared with the control group with the negative control group in 3 time periods (P > 0.05). The histopathological results of the liver and kidney showed that there was no difference in the between the negative control and positive control groups and the control group in the 10-and 20-day periods, and they had a normal structure. However, after the 30-day time period a reversible cellular inflammation in the liver and mild kidney necrosis was seen in the positive control group versus the control and negative control groups. Conclusions: In general, it can be said that the application of nanoliposomal paromomycin sulfate formulations for topical treatment of the cutaneous leishmaniasis does not create serious side effects in the short term, but its long-term use leads to mild renal and liver side effects that requires more attention.

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Griseofulvin is an antifungal drug and is available as oral dosage forms. Development of topical treatment could be advantageous for superficial fungal infections of the skin. In this study, films prepared from the incorporation of griseofulvin-loaded liposomes in chitosan film for topical drug delivery in superficial fungal infections. The properties of the films were characterized regarding mechanical properties, swelling, ability to transmit vapor, drug release, thermal behavior, and antifungal efficacy against Microsporum gypseum and Epidermophyton floccosum. The presence of liposomes led to decreased mechanical properties but lower swelling ratio. Higher amount of drug permeation and rate of flux were obtained by liposomes incorporated in films compared to liposomal formulations. Antifungal efficacy of formulations was confirmed against two species of dermatophytes in vitro. Therefore, two concepts of using vesicular carrier systems and biopolymeric films have been combined and this topical novel composite film has the potential for griseofulvin delivery to superficial fungal infections.

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Background and objective: Previous studies have demonstrated the anti-cancer effects of silymarin (SLM). However, the low bioavailability of SLM has restricted its use. This study investigated the toxic effect of nanostructured SLM encapsulated in micelles (Nano-SLM) on the growth of the HT-29 human colon cancer cell line. Materials and methods: HT-29 cells were treated with 25 μM/mL of SLM or Nano-SLM for 48 h. MTT and colony formation assays were used to assess the cytotoxicity and proliferation of HT-29 cells, respectively. The cells were stained with annexin V/PI for assessment of apoptosis. Results: MTT assays revealed that Nano-SLM treatment was able to exert a more pronounced toxic effect on the HT-29 cells as compared to free SLM treatment (p < 0.01). In the Nano-SLM-treated cells, colony numbers were significantly reduced in comparison to the free SLM-treated cells (p < 0.01). Apoptotic and necrotic indexes of Nano-SLM-treated HT-29 cells were also significantly increased in comparison to those of the free SLM-treated cells (p < 0.01). The viability, proliferation and apoptosis of healthy cells (NIH-3T3 cells) were not changed in response to Nano-SLM or SLM. Conclusions: Our results indicate that Nano-SLM enhances the anti-cancer effects of SLM against human colon cancer cells.