Topical delivery andin vivoantileishmanial activity of paromomycin-loaded liposomes for treatment of cutaneous leishmaniasis

Abstract

The present study aimed to evaluate the potential of liposomes loaded with paromomycin (PA), an aminoglycoside antibiotic associated with poor skin penetration, for the topical treatment of cutaneous leishmaniasis (CL). Fluid liposomes were prepared and characterized for particle size, zeta potential, and drug entrapment. Permeation studies were performed with two in vitro models: intact and stripped skin. The antileishmanial activity of free and liposomal PA was evaluated in BALB/c mice infected by Leishmania (L.) major. Drug entrapment ranged from 10 to 14%, and the type of vesicle had little influence on this parameter. Particle size and polydispersity index of the vesicles composed by phosphatidylcholine (PC) and PC/cholesterol (Chol) ranged from of 516 to 362 nm and 0.7 to 0.4, respectively. PA permeation across intact skin was low, regardless of the formulation tested, while drug penetration into skin (percent of the applied dose) from PC (7.2 +/- 0.2%) and PC/Chol (4.8 +/- 0.2%) liposomes was higher than solution (1.9 +/- 0.1%). PA-loaded liposomes enhanced in vitro drug permeation across stripped skin and improved the in vivo antileishmanial activity in experimentally infected mice. Our findings suggest that the liposomes represent a promising alternative for the topical treatment of CL using PA.

Drug Targeting to Macrophages With Solid Lipid Nanoparticles Harboring Paromomycin: an In Vitro Evaluation Against L. major and L. tropica

“…PM formulations have some disadvantages, including a short half-life in plasma and rapid renal excretion (being a hydrophilic molecule with high molecular weight). All these factors decrease the concentration of PM at the sites of action, e.g., the reduction of PM oral absorption, thus making the oral administration of PM inefficient (8,9,12,14). According to the data obtained from clinical trials, the effect of the topical form of PM for the treatment of cutaneous leishmaniasis has been promising, but due to the powerful barrier nature of the skin, it is not effective (16)(17)(18).…”

“…In recent years, colloidal carriers, such as liposomes, emulsions, and polymeric nanoparticles, have been very promising in improving the bioavailability of the active pharmaceutical ingredients (9,42,43). In one recent study, PM-loaded liposomes were developed and investigated as a drug delivery system (8,9,12,14). The effect of PM formulated with stearylamine-bearing liposome on visceral leishmaniasis was investigated by Banerjee et al (8).…”

“…Due to its chemical structure, PM is a hydrophilic compound with a high molecular weight. Its physicochemical properties contribute to insufficient concentration of PM at the sites of infection after topical administration (12). The lack of an effective drug against CL has recently prioritized the creation of new, alternative therapeutic drugs.…”

Combination Therapy with Paromomycin-Associated Stearylamine-Bearing Liposomes Cures Experimental Visceral Leishmaniasis through Th1-Biased Immunomodulation

“…Williams et al (47) strated parasite clearance only from the liver of L. donovaniinfected mice, with single-or double-dose treatment with nonionic-surfactant vesicular formulations of PM (47). Recently, liposomal formulations of PM were used as a topical treatment against CL to show the enhanced skin permeation and retention capacity of PM (10,24). We, for the first time, used PC-SA liposome-associated PM as a combination drug against experimental VL to achieve 88 to 98% parasite clearance from bone marrow, the liver, and the spleen, with a single-shot delivery.…”

Topical Treatment Modalities for Old World Cutaneous Leishmaniasis: A Review

“…Topical application of the liposomal form of paromomycin, experimentally evaluated in vivo, is believed to provide a promising effective topical treatment for CL (Carneiro et al, 2010).…”