ABSTRACT
Benzoxonium chloride is an anti-infective agent that is used as anti-septic drugs for disinfection of the mucus membrane, skin surface and anti-bacterial, and it is also found to be effective against cutaneous leishmaniasis. The present study aims to evaluate the leishmanicidal activity of benzoxonium chloride and niosomal forms against Leishmania tropica stages. Benzoxonium chloride niosomes were prepared by the thin film hydration method and evaluated for morphology, particle size and release study and encapsulation efficiency. This study measured the cytotoxicity, leishmanicidal activity against promastigote and intra macrophage amastigote, apoptosis, and mRNA transcripts by quantitative real time PCR (qPCR) of free solution and niosomal-encapsulated benzoxonium chloride. Span/Tween 60 niosomal formulation of benzoxonium chloride showed superior physical stability and high encapsulation efficiency (96%) than the other forms. Release from the formulations showed that the Span/Tween 60 containing drug had a milder gradient so that 10% of the drug was not released after 4 h. The benzoxonium chloride and niosomal forms inhibited the in vitro growth of promastigote and amastigote forms of L. tropica after 48 h of incubation and represented IC50 values of 90.7 ± 2.7 and 25.4 ± 0.6 µg/ mL, respectively. The rate of apoptosis in niosomal formulations was approximately equal to the positive control (meglumine antimoniate) at the same concentration. Also, an increase in the concentration of this drug reduced the expression of IL-10, but increased the expression of IL-12. The niosomal formulations provided improved anti-leishmanial activities of benzoxonium chloride and played an immunomodulatory role as the mode of action in the treatment of anthroponotic CL.
ABSTRACT
A simple efficacious topical treatment for cutaneous leishmaniasis (CL) is still an unresolved challenge. This study aimed to evaluate the efficacy of the topical use of thioxolone plus benzoxonium chloride (Thio-Ben) tincture in combination with cryotherapy in comparison with intralesional meglumine antimoniate (Glucantime) along with cryotherapy in treating anthroponotic CL (ACL). The study was conducted in Leishmaniasis Center in Dadbin Health Care Clinic, Kerman, Iran. Sixty-four CL lesions were randomly assigned to receive Thio-Ben plus cryotherapy (TC) (n = 32) or Glucantime plus cryotherapy (GC) (n = 32). Thio-Ben was used topically every other day and Glucantime was used intralesionally once a week for a maximum of 3 months. In both study groups, cryotherapy was administered using liquid nitrogen once every 2 weeks. Of 64 recruited lesions, 47 lesions completed the study protocol. Twenty lesions (91%) in TC group and 23 lesions (92%) in GC group showed complete cure. TC group showed faster clinical response. Pain, hypersensitivity reaction, dizziness, and nausea were only seen in GC group. This study showed that the topical use of Thio-Ben combined with cryotherapy has a good efficacy in treating ACL with the benefit that Thio-Ben has more patient compliance and less side effects than intralesional Glucantime.
