Journal Article

Sodium stibogluconate loaded nano-deformable liposomes for topical treatment of leishmaniasis: macrophage as a target cell

Khan, Gul Majid, Din, Fakhar Ud, Dar, M. Junaid

2018

Overview

Topical drug delivery against cutaneous leishmaniasis (CL) signifies an effective alternate for improving the availability and reducing the toxicity associated with the parenteral administration of conventional sodium stibogluconate (SSG) injection. The basic aim of the study was to develop nano-deformable liposomes (NDLs) for the dermal delivery of SSG against CL. NDLs were formulated by a modified thin film hydration method and optimized via Box-Behnken statistical design. The physicochemical properties of SSG-NDLs were established in terms of vesicle size (195.1 nm), polydispersity index (0.158), zeta potential (−32.8 mV), and entrapment efficiency (35.26%). Moreover, deformability index, in vitro release, and macrophage uptake studies were also accomplished. SSG-NDLs were entrapped within Carbopol gel network for the ease of skin application. The ex vivo skin permeation study revealed that SSG-NDLs gel provided 10-fold higher skin retention towards the deeper skin layers, attained without use of classical permeation enhancers. Moreover, in vivo skin irritation and histopathological studies verified safety of the topically applied formulation. Interestingly, the cytotoxic potential of SSG-NDLs (1.3 mg/ml) was higher than plain SSG (1.65 mg/ml). The anti-leishmanial activity on intramacrophage amastigote model of Leishmania tropica showed that IC 50 value of the SSG-NDLs was ∼ fourfold lower than the plain drug solution with marked increase in the selectivity index. The in vivo results displayed higher anti-leishmanial activity by efficiently healing lesion and successfully reducing parasite burden. Concisely, the outcomes indicated that the targeted delivery of SSG could be accomplished by using topically applied NDLs for the effective treatment of CL.

• Publisher: Taylor & Francis,Taylor & Francis Ltd,Taylor & Francis Group
• Subject: Administration, Topical / Animals / Antimony Sodium Gluconate - administration & dosage / Antimony Sodium Gluconate - metabolism / Antiprotozoal Agents - administration & dosage / Antiprotozoal Agents - metabolism / Cutaneous leishmaniasis / Dose-Response Relationship, Drug / Drug Delivery Systems - methods / Drugs / Entrapment / Female / Leishmaniasis - drug therapy / Leishmaniasis - metabolism / Lipids / Liposomes / macrophage uptake / Macrophages - drug effects / Macrophages - metabolism / Mice / Mice, Inbred BALB C / Molecular weight / nano-deformable liposomes / Nanoparticles - administration & dosage / Nanoparticles - metabolism / Optimization / Organ Culture Techniques / Parasites / Parasitic diseases / Pharmacy / Rats / Skin Absorption - drug effects / Skin Absorption - physiology / Sodium / sodium stibogluconate / Surfactants / transfersomes / Treatment Outcome