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

de Mattos CB, Argenta DF, Melchiades Gde L, Cordeiro MN, Tonini ML, Moraes MH, Weber TB, Roman SS, Nunes RJ, Teixeira HF, Steindel M, Koester LS - Int J Nanomedicine (2015)

Bottom Line: Nanoemulsions are drug delivery systems that may increase the penetration of lipophilic compounds through the skin, enhancing their topical effect.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.

View Article: PubMed Central - PubMed

Affiliation: Faculdade de Farmácia, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

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.

No MeSH data available.


Related in: MedlinePlus

Inhibitory effects of nanoemulsions on Leishmania amazonensis in vitro tested 24 hours after the preparation of formulations.Notes: Adherent THP-1 cells were infected at a ratio of 1:10 cell/parasite L. amazonensis and treated for 48 hours with free SC and SC loaded into nanoemulsions in a concentration range of 0.375–20 µg·mL−1. Results are expressed as the mean ± SD of the percent inhibition of parasite growth (n=3).Abbreviations: LP20, soybean lecithin and polysorbate 20; LP80, soybean lecithin and polysorbate 80; SC, (E)-3-(3-nitrophenyl)-1-(3,4,5-trimethoxyphenyl) prop-2-en-1-one; SD, standard deviation; SP20, sorbitan monooleate and polysorbate 20; SP80, sorbitan monooleate and polysorbate 80.
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f8-ijn-10-5529: Inhibitory effects of nanoemulsions on Leishmania amazonensis in vitro tested 24 hours after the preparation of formulations.Notes: Adherent THP-1 cells were infected at a ratio of 1:10 cell/parasite L. amazonensis and treated for 48 hours with free SC and SC loaded into nanoemulsions in a concentration range of 0.375–20 µg·mL−1. Results are expressed as the mean ± SD of the percent inhibition of parasite growth (n=3).Abbreviations: LP20, soybean lecithin and polysorbate 20; LP80, soybean lecithin and polysorbate 80; SC, (E)-3-(3-nitrophenyl)-1-(3,4,5-trimethoxyphenyl) prop-2-en-1-one; SD, standard deviation; SP20, sorbitan monooleate and polysorbate 20; SP80, sorbitan monooleate and polysorbate 80.

Mentions: In vitro leishmanicidal activity of SC nanoemulsions was evaluated in order to attest the possible potentiation of this activity in these reduced water solubility molecules carrier systems. Our results indicate that the nanoemulsions LP20 and SP80 were able to maintain the leishmanicidal activity of this molecule against amastigote forms of L. amazonensis (Table 4). Leishmanicidal assays were repeated 60 days after the preparation of the nanoemulsions in order to evaluate the stability of the formulations in which LP20 showed an IC50 of 1.13 µg·mL−1, whereas SP80, SP20, and LP80 presented values higher than 20 µg·mL−1 (data not shown). The highest percentage of inhibition of parasitic growth was observed after treatment with LP20 in both times stipulated. This formulation showed approximately 100% of inhibition at most concentrations tested in 24 hours (Figure 8), and presented a slight reduction on its profile after 60 days (data not shown). Cell viability was determined by the MTT technique only for the carrier systems that presented higher antileishmanial activity (ie, LP20 and SP80) (Table 4). Selectivity index (SI) for LP20 and SP80 was 27.97 and 67.42, respectively, which are higher values than the threshold suggested by Grogl et al53 as satisfactory for in vitro tests (>5.0). Although LP20 presented lower SI than SP80, this formulation maintained its inhibition profile against L. amazonensis amastigote forms and, therefore, was found to be the best formulation. Furthermore, the drugs used in the current treatment of CL present lower SI values than those found in our results. Glucantime presented SI values of 0.8 and 0.5, against L. major and Leishmania infantum, respectively.54,55 When evaluated against L. amazonensis, Glucantime presented SI in range of 0.3–2.4.56 The SI of miltefosine was 0.26 against Leishmania donovani.57 Recent studies investigated the antileishmanial activity of extracts of Hypericum spp., Syzygium cumini essential oil and α-pinene against L. amazonensis and found SI values ranging from 1.2 to 4.0, 10.2 to 16.1, and 21.5 to 27.2, respectively.56,58 A novel diselenide chitosan hydrogel formulation presented SI of 1.8 against L. major.59 Although the positive control presented a good result in this in vitro study, it is worth emphasizing that some cases of Amphotericin B resistance against Leishmania spp. have been recently reported.60,61 Taken together, the results of these studies justify the investigation of new drug candidates for Leishmaniasis treatment.


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

de Mattos CB, Argenta DF, Melchiades Gde L, Cordeiro MN, Tonini ML, Moraes MH, Weber TB, Roman SS, Nunes RJ, Teixeira HF, Steindel M, Koester LS - Int J Nanomedicine (2015)

Inhibitory effects of nanoemulsions on Leishmania amazonensis in vitro tested 24 hours after the preparation of formulations.Notes: Adherent THP-1 cells were infected at a ratio of 1:10 cell/parasite L. amazonensis and treated for 48 hours with free SC and SC loaded into nanoemulsions in a concentration range of 0.375–20 µg·mL−1. Results are expressed as the mean ± SD of the percent inhibition of parasite growth (n=3).Abbreviations: LP20, soybean lecithin and polysorbate 20; LP80, soybean lecithin and polysorbate 80; SC, (E)-3-(3-nitrophenyl)-1-(3,4,5-trimethoxyphenyl) prop-2-en-1-one; SD, standard deviation; SP20, sorbitan monooleate and polysorbate 20; SP80, sorbitan monooleate and polysorbate 80.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562752&req=5

f8-ijn-10-5529: Inhibitory effects of nanoemulsions on Leishmania amazonensis in vitro tested 24 hours after the preparation of formulations.Notes: Adherent THP-1 cells were infected at a ratio of 1:10 cell/parasite L. amazonensis and treated for 48 hours with free SC and SC loaded into nanoemulsions in a concentration range of 0.375–20 µg·mL−1. Results are expressed as the mean ± SD of the percent inhibition of parasite growth (n=3).Abbreviations: LP20, soybean lecithin and polysorbate 20; LP80, soybean lecithin and polysorbate 80; SC, (E)-3-(3-nitrophenyl)-1-(3,4,5-trimethoxyphenyl) prop-2-en-1-one; SD, standard deviation; SP20, sorbitan monooleate and polysorbate 20; SP80, sorbitan monooleate and polysorbate 80.
Mentions: In vitro leishmanicidal activity of SC nanoemulsions was evaluated in order to attest the possible potentiation of this activity in these reduced water solubility molecules carrier systems. Our results indicate that the nanoemulsions LP20 and SP80 were able to maintain the leishmanicidal activity of this molecule against amastigote forms of L. amazonensis (Table 4). Leishmanicidal assays were repeated 60 days after the preparation of the nanoemulsions in order to evaluate the stability of the formulations in which LP20 showed an IC50 of 1.13 µg·mL−1, whereas SP80, SP20, and LP80 presented values higher than 20 µg·mL−1 (data not shown). The highest percentage of inhibition of parasitic growth was observed after treatment with LP20 in both times stipulated. This formulation showed approximately 100% of inhibition at most concentrations tested in 24 hours (Figure 8), and presented a slight reduction on its profile after 60 days (data not shown). Cell viability was determined by the MTT technique only for the carrier systems that presented higher antileishmanial activity (ie, LP20 and SP80) (Table 4). Selectivity index (SI) for LP20 and SP80 was 27.97 and 67.42, respectively, which are higher values than the threshold suggested by Grogl et al53 as satisfactory for in vitro tests (>5.0). Although LP20 presented lower SI than SP80, this formulation maintained its inhibition profile against L. amazonensis amastigote forms and, therefore, was found to be the best formulation. Furthermore, the drugs used in the current treatment of CL present lower SI values than those found in our results. Glucantime presented SI values of 0.8 and 0.5, against L. major and Leishmania infantum, respectively.54,55 When evaluated against L. amazonensis, Glucantime presented SI in range of 0.3–2.4.56 The SI of miltefosine was 0.26 against Leishmania donovani.57 Recent studies investigated the antileishmanial activity of extracts of Hypericum spp., Syzygium cumini essential oil and α-pinene against L. amazonensis and found SI values ranging from 1.2 to 4.0, 10.2 to 16.1, and 21.5 to 27.2, respectively.56,58 A novel diselenide chitosan hydrogel formulation presented SI of 1.8 against L. major.59 Although the positive control presented a good result in this in vitro study, it is worth emphasizing that some cases of Amphotericin B resistance against Leishmania spp. have been recently reported.60,61 Taken together, the results of these studies justify the investigation of new drug candidates for Leishmaniasis treatment.

Bottom Line: Nanoemulsions are drug delivery systems that may increase the penetration of lipophilic compounds through the skin, enhancing their topical effect.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.

View Article: PubMed Central - PubMed

Affiliation: Faculdade de Farmácia, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

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.

No MeSH data available.


Related in: MedlinePlus