Nanoemulsions containing amphotericin b and paromomycin for the treatment of cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) is a vector-borne disease characterized by skin lesions that can evolve into high-magnitude ulcerated lesions. Thus, this study aimed to develop an innovative nanoemulsion (NE) with clove oil, Poloxamer® 407, and multiple drugs, such as amphotericin B (AmB) and paromomycin (PM), for use in the topical treatment of CL. METHODS: Droplet size, morphology, drug content, stability, in vitro release profile, in vitro cytotoxicity on RAW 264.7 macrophages, and antileishmanial activity using axenic amastigotes of Leishmania amazonensis were assessed for NEs. RESULTS: After optimizing the formulation parameters, such as the concentration of clove oil and drugs, using an experimental design, it was possible to obtain a NE with an average droplet size of 40 nm and a polydispersion index of 0.3, and these parameters were maintained throughout the 365 days. Furthermore, the NE showed stability of AmB and PM content for 180 days under refrigeration (4 °C), presented a pH compatible with the skin, and released modified AmB and PM. NE showed the same toxicity as free AmB and higher toxicity than free PM against RAW 264.7 macrophages. The same activity as free AmB, and higher activity than free PM against amastigotes L. amazonensis. CONCLUSION: It is possible to develop a NE for the treatment of CL; however, complementary studies regarding the antileishmanial activity of NE should be carried out.

Promising natural products for the treatment of cutaneous leishmaniasis: A review of in vitro and in vivo studies.

Although there are available treatments for cutaneous leishmaniasis (CL), the drugs used are far from ideal, toxic, and costly, in addition to the challenge faced by the development of resistance. Plants have been used as a source of natural compounds with antileishmanial action. However, few have reached the market and become phytomedicines with registration in regulatory agencies. Difficulties related to the extraction, purification, chemical identification, efficacy, safety, and production in sufficient quantity for clinical studies, hinder the emergence of new effective phytomedicines against leishmaniasis. Despite the difficulties reported, the major research centers in the world see that natural products are a trend concerning the treatment of leishmaniasis. The present work consists of a literature review of articles with in vivo studies, covering the period from January 2011 to December 2022, providing an overview of promising natural products for CL treatment. The papers show encouraging antileishmanial action of natural compounds with reduced parasite load and lesion size in animal models, suggesting new strategies for the treatment of the disease. The results reported in this review show advances in using natural products as safe and effective formulations, which can stimulate clinical studies to establish clinical therapy. In conclusion, the information in this review article serves as a preliminary basis for establishing a therapeutic protocol for future clinical trials that can validate the safety and efficacy of natural compounds, providing the development of affordable and safe phytomedicines for the treatment of CL.

Pharmaceutical nanotechnology applied to phthalocyanines for the promotion of antimicrobial photodynamic therapy: A literature review.

Phthalocyanines are photosensitizers activated by light at a specific wavelength in the presence of oxygen and act through the production of Reactive Oxygen Species, which simultaneously attack several biomolecular targets in the pathogen agent and, therefore, have multiple and variable action sites. This nonspecific action site bypasses conventional resistance mechanisms. Antimicrobial Photodynamic Therapy (aPDT) is safe, easy to implement and, unlike conventional agents, may have a wide activity spectrum of photoantimicrobials. This work is a systematic review of the literature based on nanocarriers containing phthalocyanines in aPDT against bacteria, fungi, viruses, and protozoa. The search was performed in two different databases (MEDLINE/PubMed and Web of Science) between 2011 and May 2021. Nanocarriers often improve the action or are equivalent to free drugs, but their use allows substituting the organic solvent in the case of hydrophobic phthalocyanines, allowing for a safer application of aPDT with the possibility of prolonged release. In the case of hydrophilic phthalocyanines, they would allow for nonspecific site delivery with a possibility of cellular internalization. A single infectious lesion can have multiple microorganisms, and PDT with phthalocyanines is an interesting treatment given its ample spectrum of action. It is possible to highlight the upconversion nanosystems, which allow for the activation of phthalocyanine in deeper tissues by using longer wavelengths, as a system that has not yet been studied, but which could provide treatment solutions. The use of nanocarriers containing phthalocyanines requires more study to establish the use of aPDT in humans.