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

Abstract

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 IC50 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.

Development and Characterization of a Semi-Solid Dosage Form of Meglumine Antimoniate for Topical Treatment of Cutaneous Leishmaniasis

“…The same behavior was observed for the MA solution, although a lower amount of Sb V was detected. Similar results were obtained by Dar et al (2018), who tested nano-deformable liposomes with sodium stibogluconate and the same liposomes in a Carbopol gel on rat skin, and observed a low percentage of Sb V permeated into the receptor compartment and a high percentage was retained in the skin [21]. Other studies with liposomes encapsulating MA, MA combined with oleic acid and MA plus stearylamine also showed low permeation of Sb V across the skin barrier and high retention in mouse skin [22,23].…”

“…The rheological properties of topical semi-solid dosage forms are important because they influence skin spreadability, adhesion and retention in the application site [21]. The rheological analysis indicated that the MA gel is a pseudoplastic fluid, like most gels reported in the literature, which is ideal for topical administration [37].…”

“…Regarding antimonials, there are few data available on semi-solid dosage forms for topical administration. The development and characterization of liposomes loading sodium stibogluconate and MA has been described [21,22,23].…”

Preparation of Encapsulated Resveratrol Liposome Thermosensitive Gel and Evaluation of Its Capability to Repair Sciatic Nerve Injury in Rats

“…It identifies the relationship between variables and response to obtain the most appropriate conditions for preparation [23]. In the present study, a Box-Behnken Design (BBD), a common response surface methodology, was used to optimize the formulation of RSV-Lips [24,25]. The weight ratio of phospholipid to cholesterol, the weight ratio of phospholipid to drug, and the ultrasonic power value were used as independent variables, while the entrapment efficiency and drug loading capacity were used as response values.…”

Potential Use of Gluconate in Cancer Therapy

“…Stibogluconate (sodium antimony gluconate, sodium stibugluconate, pentostam, stibium Sb gluconate) is an anti-parasitic drug that incorporates gluconate into the drug substance. It belongs to the anti-leishmaniasis group of drugs called pentavalent-(V)-antimony compounds in which antimony (Sb) is used (17–19). It has been suggested that stibogluconate acts through immune system stimulation, mainly by increasing the amount of peripheral IFN-γ + T cells (20).…”