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

Abstract

Cutaneous leishmaniasis (CL) is treated with painful intralesional injections of meglumine antimoniate (MA). With the aim of developing an alternative topical treatment for CL, a gel-based formulation with 30% MA was prepared and its physicochemical properties, stability and rheological behavior were studied. The following were assessed: drug release on propylene hydrophilic membranes ex vivo human skin permeation, tolerance in healthy volunteers, cytotoxicity in three cell lines and anti-leishmanial activity against Leishmania infantum promastigotes and amastigotes. The MA gel formulation was found to have suitable pH, and good spreadability and stability. Low quantities of pentavalent antimony (SbV) were observed in release and permeation tests, whereas retention was high in both non-damaged and damaged skin (71,043.69 ± 10,641.57 and 10,728 ± 2254.61 µg/g/cm2 of SbV, respectively). The formulation did not have a toxic effect on the cell lines, and presented lower SbV IC50 values against amastigotes (15.76 ± 4.81 µg/mL) in comparison with the MA solution. The high amount of drug retained in the skin and the SbV IC50 values obtained suggest that this semi-solid dosage form has potential as an alternative treatment of CL.

Topical Amphotericin B Semisolid Dosage Form for Cutaneous Leishmaniasis: Physicochemical Characterization, Ex Vivo Skin Permeation and Biological Activity

“…The high porosity percentage of the AmB gel was corroborated by SEM images, which revealed undulating layers uniformly arranged and spaces between the layers, resembling holes or cavities. We reported similar levels of swelling, degradation and porosity in a previously characterized meglumine antimoniate Sepigel 305 ® [35].…”

Biophysical and ultrasonographic changes of acute Old World cutaneous leishmaniasis skin lesions in comparison with uninvolved skin: A possible tool for non‐invasive early detection and treatment outcome assessment

“…Recently, TEWL values have been considered as criteria for SC integrity in CL clinical trials and they have shown decrease after treatment. 23,24 Then, greater amount of TEWL in lesions was predictable. SC hydration was increased after CL lesion treatment 23,24 and it was lower in lesions according to our results too, but the difference was not significant.…”

“…TEWL evaluation showed greater amount in lesions. Recently, TEWL values have been considered as criteria for SC integrity in CL clinical trials and they have shown decrease after treatment 23,24 . Then, greater amount of TEWL in lesions was predictable.…”

Antifungal and Antiparasitic Drug Delivery

“…The originality of the new formulations proposed are usually based on the selection of already approved excipients along with the active components, such as Montanide™ Petgel A as vaccine adjuvant [1], poly(vinyl alcohol) [2], Poloxamer 407™ [3], a combination of Capryol 90™, Peceol™ and Labrasol™ [4], dextran and maltodextrin [5], a combination of modified chitosan nanoparticles with a standardized extract of cultured Lentinula edodes mycelia (AHCC™) [6], ground calcium carbonate [7], poly (d,l-lactide-co-glycolide) 50:50 [8] and Sepigel 305™ [9]. Only in one paper [10], authors have synthesized a new material based on copolymers of poly(ethyleneglycol) and poly(ε-caprolactone) conjugated with retinol as drug vehicle.…”

“…Berenguer et al developed and characterized a semi-solid gel dosage form of meglumine antimoniate for the topical treatment of cutaneous leishmaniasis [9]. The gel is easy to prepare and its main excipient is Sepigel 305™.…”