Colloidal, in vitro and in vivo anti-leishmanial properties of transfersomes containing paromomycin sulfate in susceptible BALB/c mice

• Published in: Acta tropica 2012-10, Vol.124 (1), p.33-41
• Main Authors: Bavarsad, Neda, Fazly Bazzaz, Bibi Sedigheh, Khamesipour, Ali, Jaafari, Mahmoud Reza
• Format: Article
• Language: English
• Subjects: Administration, Topical; Amastigotes; Animals; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiprotozoal Agents - administration & dosage; Antiprotozoal Agents - pharmacokinetics; Antiprotozoal Agents - pharmacology; Biological and medical sciences; Chemistry, Pharmaceutical; colloidal properties; Cutaneous leishmaniasis; cytotoxicity; Disease Models, Animal; encapsulation; ethanol; Female; General aspects; Human protozoal diseases; Humans; Infectious diseases; L. major; Leishmania major; Leishmania major - drug effects; Leishmaniasis, Cutaneous - drug therapy; Leishmaniasis, Cutaneous - parasitology; Leshmaniasis; macrophages; Medical sciences; Mice; Mice, Inbred BALB C; Parasite Load; parasites; Parasitic diseases; Parasitic Sensitivity Tests; Paromomycin; Paromomycin - administration & dosage; Paromomycin - pharmacokinetics; Paromomycin - pharmacology; Pharmacology. Drug treatments; phosphatidylcholines; promastigotes; Protozoal diseases; Skin - pathology; sodium; spleen; Spleen - parasitology; therapeutics; Topical treatment; Transfersomes; Treatment Outcome; zeta potential
• ISSN: 0001-706X; 1873-6254
• DOI: 10.1016/j.actatropica.2012.06.004

This study showed PMTFs prepared with 2% of Na-Ch with and without 5% ethanol might be useful as a candidate for the treatment of CL. [Display omitted] ► Topical paromomycin transfersomes cured L. major lesions on BALB/c mice. ► Topical paromomycin transfersomes decreased significantly the spleen parasite burden. ► Transfersomes increased significantly the paromomycin penetration through skin mice. The aim of this study was to develop transfersomal formulation with respect to dermal delivery of paromomycin sulfate (PM) for possible topical therapy of cutaneous leishmaniasis (CL). PM transfersomal formulations (PMTFs) with different percent of soy phosphatidylcholine, sodium cholate (Na-Ch) and ethanol were prepared and characterized for the size, zeta potential and encapsulation efficiency. The results showed that the most stable formulations with suitable colloidal properties were obtained by 2% Na-Ch which had average size of around 200nm. The in vitro permeation study using Franz diffusion cells fitted with mouse skin at 37°C for 24h showed that almost 23% of the PMTFs applied penetrated the mouse skin, and the amount retained in the skin was about 67% for both formulations; however, the percent of penetration and retention for PM conventional cream was 49 and 13, respectively. The 50% effective doses of PMTFs against Leishmania major promastigotes and amastigotes in culture were significantly less than cream and/or solution of PM. Selected PMTFs and empty transfersomes showed no cytotoxicity in J774 A.1 mouse macrophage cell line. Selected PMTFs 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