Development and evaluation of zinc phthalocyanine nanoemulsions for use in photodynamic therapy forLeishmaniaspp.

Abstract

Photodynamic therapy (PDT) combines light with photosensitizers (PS) for production of reactive oxygen species (ROS) that can kill infectious microorganisms such as bacteria, fungi and protozoa. The application of nanotechnology has enabled the advancement of PDT because many PS are insoluble in water, necessitating a nanocarrier as a physiologically acceptable carrier. Nanoemulsions are efficient nanocarriers for solubilizing liposoluble drugs, like the PS, in water. Cutaneous (CL) and mucocutaneous leishmaniasis (ML) are caused by different species of the genus Leishmania, transmitted to humans by sandfly bites. Parasites are hosted in skin macrophages producing ulcerative lesions. Thus, a topical treatment, effective and inexpensive, for CL and ML is preferable to systemic interventions. There are topical treatments like paromomycin and amphotericin B, but they have many local side effects or a very high cost, limiting their use. This work aimed to develop a zinc phthalocyanine (photosensitizer) oil-in-water nanoemulsion, essential clove oil and polymeric surfactant (Pluronic F127) for the formulation of a topical delivery system for use in PDT against Leishmania amazonensis and Leishmania infantum. The nanoemulsion was produced by a high-energy method and characterized by size, polydispersity, morphology, pH, content and stability studies. The toxicity in the dark and the photobiological activity of the formulations were evaluated in vitro for Leishmania and macrophages. The formulation presented was pH compatible with topical use, approximately 30 nm in size, with a polydispersity index ≤0.1 and remained stable at room and refrigerator temperature during the stability study (60 days). The zinc phthalocyanine nanoemulsion is effective in PDT against Leishmania spp.; use against skin infections can be a future application of this topical formulation, avoiding the use of oral or injectable medications, decreasing systemic adverse effects.

Digitoxigenin presents an effective and selective antileishmanial action against Leishmania infantum and is a potential therapeutic agent for visceral leishmaniasis

“…Antileishmanial candidates have been incorporated into delivery systems to improve their therapeutic efficacy and reduce the toxicity of the corresponding pure compounds (Bruni et al 2017;Wagner et al 2019). In previous studies, we showed that micellar compositions using Poloxamer 407 (Pluronic® F127-based polymeric micelles proved effective in mammalian models against Leishmania infection (Duarte et al 2016;Oliveira-de-Siqueira et al 2017;Mendonça et al 2019). In a similar fashion, we also developed a clioquinol (ICHQ)-containing Pluronic® F127 polymeric micelle system Fig.…”

Nanoemulsion as a Platform for Iontophoretic Delivery of Lipophilic Drugs in Skin Tumors

“…It is noteworthy that the developed nanoemulsion was able to solubilize a higher concentration of ZnPc than other lipid release systems described in the literature [36,37,38,39]. For instance, ZnPc was incorporated in liposome [36], microemulsion [37], and nanoemulsion [38] at the concentrations of 1 µg/mL, 7 µg/mL and 35 µg/mL, respectively, while the nanoemulsion developed in this work incorporated about 50 µg/mL of ZnPc (Table 1).…”

<p>Bifunctional Therapeutic Application of Low-Frequency Ultrasound Associated with Zinc Phthalocyanine-Loaded Micelles</p>

“…49 However, compared to nanoemulsions, ZnPc concentration found in the micelles was up to 4-fold lower. 25,52 Although the concentration of ZnPc solubilized in such oil-containing delivery systems is higher than that found in the micelles, it is reasonable to infer that the lipid content of emulsions could restore the LTRs formed in the skin by LFU treatment, resulting in a drastic reduction of drug transport through the skin by sonophoresis. Indeed, some studies have suggested that the sonophoretic transport of drugs from liposomes resulted in lower drug penetration.…”