Nanoemulsions containing a synthetic chalcone as an alternative for treating cutaneous leshmaniasis: optimization using a full factorial design

Abstract

Nanoemulsions are drug delivery systems that may increase the penetration of lipophilic compounds through the skin, enhancing their topical effect. Chalcones are compounds of low water solubility that have been described as promising molecules for the treatment of cutaneous leishmaniasis (CL). In this context, the aim of this work was to optimize the development of a nanoemulsion containing a synthetic chalcone for CL treatment using a 2 2 full factorial design. The formulations were prepared by spontaneous emulsification and the experimental design studied the influence of two independent variables (type of surfactant – soybean lecithin or sorbitan monooleate and type of co-surfactants – polysorbate 20 or polysorbate 80) on the physicochemical characteristics of the nanoemulsions, as well as on the skin permeation/retention of the synthetic chalcone in porcine skin. In order to evaluate the stability of the systems, the antileishmanial assay was performed against Leishmania amazonensis 24 hours and 60 days after the preparation of the nanoemulsions. The formulation composed of soybean lecithin and polysorbate 20 presented suitable physicochemical characteristics (droplet size 171.9 nm; polydispersity index 0.14; zeta potential −39.43 mV; pH 5.16; and viscosity 2.00 cP), drug content (91.09%) and the highest retention in dermis (3.03 µg·g −1 ) – the main response of interest – confirmed by confocal microscopy. This formulation also presented better stability of leishmanicidal activity in vitro against L . amazonensis amastigote forms (half maximal inhibitory concentration value 0.32±0.05 µM), which confirmed the potential of the nanoemulsion soybean lecithin and polysorbate 20 for CL treatment.

Bromocriptine Nanoemulsion-Loaded Transdermal Gel: Optimization Using Factorial Design, In Vitro and In Vivo Evaluation

“…Before viewing the samples under a microscope, the skin samples were dehydrated using ethanol and fixed in paraffin followed by staining with hematoxylin and eosin. The formulationexposed skin sample was compared with the control (untreated) sample for any signs of irritation or incompatibility (35,36). Three different sites of each specimen were evaluated for possible abnormalities due to long-term exposure to the formulation (27).…”

Promising nanotherapy in treating leishmaniasis

“…This nanoemulsion improved activity against intracellular amastigotes of L. amazonensis in THP-1 cells. Additionally, considering the parasitic inhibition profile, this formulation demonstrated both stability and maintenance of leishmanicidal activity (Koester et al, 2015). Lopes et al (2012) proposed the encapsulated oryzalin containing dinitroanilines in SLN for parenteral administration.…”

Nanoemulsions with Chloroaluminium Phthalocyanine and Paromomycin for Combined Photodynamic and Antibiotic Therapy for Cutaneous Leishmaniasis

“…This kind of formulation has already been used for the delivery of a number of drugs, such as cyclosporine and pentyl gallate, for the treatment of dermatological conditions such as psoriasis and herpes [ 17 18 ]. NEs loaded with zinc-phtalocyanine or containing other compounds, such as chalcones and Amphotericin B, have also been tested as treatments of CL [ 19 20 21 ].…”