Amphotericin-B-loaded polymer-functionalized reduced graphene oxides for Leishmania amazonensis chemo-photothermal therapy

Two platforms based on reduced graphene oxide (rGO) functionalized with Pluronic® P123 (rGO-P123) and polyethyleneimine – PEI (rGO-PEI) polymers and loaded with amphotericin B (AmB) were fabricated and tested against Leishmania amazonensis, which can cause cutaneous and diffuse cutaneous leishmanias...

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Published in:Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2022-01, Vol.209 (Pt 1), p.112169-112169, Article 112169
Main Authors: Vitorino, Letícia S., dos Santos, Thiago C., Bessa, Isabela A.A., Santos, Evelyn C.S., Verçoza, Brunno R.F., de Oliveira, Luiz Augusto S., Rodrigues, Juliany C.F., Ronconi, Célia M.
Format: Article
Language:English
Subjects:
Amphotericin B
Amphotericin B - pharmacology
Animals
Chemo-photothermal therapy
Graphite
Leishmania
Leishmania amazonensis
Near-infrared light-activated drug delivery systems
Oxides
Photothermal Therapy
Polymers
Reduced graphene oxide
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Summary:Two platforms based on reduced graphene oxide (rGO) functionalized with Pluronic® P123 (rGO-P123) and polyethyleneimine – PEI (rGO-PEI) polymers and loaded with amphotericin B (AmB) were fabricated and tested against Leishmania amazonensis, which can cause cutaneous and diffuse cutaneous leishmaniasis. The materials rGO-P123 and rGO-PEI were efficiently loaded with AmB – a polyene antibiotic – which resulted in rGO-P123-AmB (0.078 mg per mg of material) and rGO-PEI-AmB (0.086 mg per mg of material). Under near-infrared (NIR) light irradiation, the amount of AmB released from rGO-PEI-AmB at pH 5.0 and 7.4 doubled in comparison to AmB released in the absence of NIR light under identical conditions. It was accompanied by a photothermal effect. Otherwise, rGO-P123-AmB did not show a significant change in AmB released in the presence and absence of NIR light. Cytotoxicity studies in mammalian host macrophages revealed that rGO-PEI and rGO-PEI-AmB were nontoxic to the host cells, whereas rGO-123 and rGO-P123-AmB were very toxic, particularly the latter. Therefore, only rGO-PEI and rGO-PEI-AmB were tested against L. amazonensis promastigotes in the presence and absence of NIR light. In vitro antiproliferative effects revealed that rGO-PEI-AmB showed a more pronounced activity against the parasite than rGO-PEI, which was improved under NIR light irradiation. Scanning-transmission electron microscopy of L. amazonensis promastigotes after incubation with rGO-PEI or rGO-PEI-AmB suggested autophagic and necrotic cell death. Thus, the facile synthesis, high AmB loading capacity and good photothermal effect make the rGO-PEI-AmB platform a promising candidate for the topical treatment of cutaneous leishmaniasis. [Display omitted] •Two near-infrared (NIR) light-activated platforms based on reduced graphene were developed.•The drug delivery systems were loaded with an antileishmanial Amphotericin B (AmB) antibiotic.•The amount of AmB released from the materials increased under NIR light irradiation.•In vitro antiproliferative effects were tested against L. amazonensis parasites.•AmB-loaded materials are promising candidates for the treatment of cutaneous leishmaniasis.
ISSN:0927-7765
1873-4367
DOI:10.1016/j.colsurfb.2021.112169