The Role of Inhaled Chitosan-Based Nanoparticles in Lung Cancer Therapy.

Lung cancer is the leading cause of cancer-related mortality worldwide, largely due to the limited efficacy of anticancer drugs, which is primarily attributed to insufficient doses reaching the lungs. Additionally, patients undergoing treatment experience severe systemic adverse effects due to the distribution of anticancer drugs to non-targeted sites. In light of these challenges, there has been a growing interest in pulmonary administration of drugs for the treatment of lung cancer. This route allows drugs to be delivered directly to the lungs, resulting in high local concentrations that can enhance antitumor efficacy while mitigating systemic toxic effects. However, pulmonary administration poses the challenge of overcoming the mechanical, chemical, and immunological defenses of the respiratory tract that prevent the inhaled drug from properly penetrating the lungs. To overcome these drawbacks, the use of nanoparticles in inhaler formulations may be a promising strategy. Nanoparticles can assist in minimizing drug clearance, increasing penetration into the lung epithelium, and enhancing cellular uptake. They can also facilitate increased drug stability, promote controlled drug release, and delivery to target sites, such as the tumor environment. Among them, chitosan-based nanoparticles demonstrate advantages over other polymeric nanocarriers due to their unique biological properties, including antitumor activity and mucoadhesive capacity. These properties have the potential to enhance the efficacy of the drug when administered via the pulmonary route. In view of the above, this paper provides an overview of the research conducted on the delivery of anticancer drug-loaded chitosan-based nanoparticles incorporated into inhaled drug delivery devices for the treatment of lung cancer. Furthermore, the article addresses the use of emerging technologies, such as siRNA (small interfering RNA), in the context of lung cancer therapy. Particularly, recent studies employing chitosan-based nanoparticles for siRNA delivery via the pulmonary route are described.

Corrigendum: Characterization of Aspergillus fumigatus Extracellular Vesicles and Their Effects on Macrophages and Neutrophils Functions.

[This corrects the article DOI: 10.3389/fmicb.2019.02008.].

Characterization of Aspergillus fumigatus Extracellular Vesicles and Their Effects on Macrophages and Neutrophils Functions.

Extracellular vesicles (EVs) has been considered an alternative process for intercellular communication. EVs release by filamentous fungi and the role of vesicular secretion during fungus-host cells interaction remain unknown. Here, we identified the secretion of EVs from the pathogenic filamentous fungus, Aspergillus fumigatus. Analysis of the structure of EVs demonstrated that A. fumigatus produces round shaped bilayer structures ranging from 100 to 200 nm size, containing ergosterol and a myriad of proteins involved in REDOX, cell wall remodeling and metabolic functions of the fungus. We demonstrated that macrophages can phagocytose A. fumigatus EVs. Phagocytic cells, stimulated with EVs, increased fungal clearance after A. fumigatus conidia challenge. EVs were also able to induce the production of TNF-α and CCL2 by macrophages and a synergistic effect was observed in the production of these mediators when the cells were challenged with the conidia. In bone marrow-derived neutrophils (BMDN) treated with EVs, there was enhancement of the production of TNF-α and IL-1ß in response to conidia. Together, our results demonstrate, for the first time, that A. fumigatus produces EVs containing a diverse set of proteins involved in fungal physiology and virulence. Moreover, EVs are biologically active and stimulate production of inflammatory mediators and fungal clearance.

Canine Leishmaniasis: An Overview of the Current Status and Strategies for Control.

Canine leishmaniasis (CanL) is a vector-borne disease caused by Leishmania infantum and is transmitted by female phlebotomine sand flies primarily between animals and secondarily to humans. The course of infection may be different from one individual dog to another, ranging from spontaneous cure to acute evolution that leads to death, if proper management and therapy are not adopted. A parasitological cure is rarely achieved and clinical recurrences in CanL are frequent. Vaccination associated with the use of topical insecticides is undoubtedly the most effective form of prevention and control of the disease. In order to integrate the most important scientific knowledge of the literature in one objective publication, this review proposes a short overview of the main points of CanL.

Mixed Formulation of Conventional and Pegylated Meglumine Antimoniate-Containing Liposomes Reduces Inflammatory Process and Parasite Burden in Leishmania infantum-Infected BALB/c Mice.

Pentavalent antimonial has been the first choice treatment for visceral leishmaniasis; however, it has several side effects that leads to low adherence to treatment. Liposome-encapsulated meglumine antimoniate (MA) arises as an important strategy for chemotherapy enhancement. We evaluated the immunopathological changes using the mixture of conventional and pegylated liposomes with MA. The mice were infected with Leishmania infantum and a single-dose treatment regimen. Comparison was made with groups treated with saline, empty liposomes, free MA, and a liposomal formulation of MA (Lipo MA). Histopathological analyses demonstrated that animals treated with Lipo MA showed a significant decrease in the inflammatory process and the absence of granulomas. The in vitro stimulation of splenocytes showed a significant increase of gamma interferon (IFN-γ) produced by CD8+ T cells and a decrease in interleukin-10 (IL-10) produced by CD4+ and CD8+ T cells in the Lipo MA. Furthermore, the Lipo MA group showed an increase in the IFN-γ/IL-10 ratio in both CD4+ and CD8+ T cell subsets. According to the parasite load evaluation using quantitative PCR, the Lipo MA group showed no L. infantum DNA in the spleen (0.0%) and 41.4% in the liver. In addition, we detected a low positive correlation between parasitism and histopathology findings (inflammatory process and granuloma formation). Thus, our results confirmed that Lipo MA is a promising antileishmanial formulation able to reduce the inflammatory response and induce a type 1 immune response, accompanied by a significant reduction of the parasite burden into hepatic and splenic compartments in treated animals.

Development and characterization of multilamellar liposomes containing pyridostigmine.

Pyridostigmine has cardioprotective activity in both free and liposomal forms. This study aimed to develop and characterize liposomal formulations of pyridostigmine. For this, a spectrophotometric ultraviolet (UV) analytical method, at 270 nm, was developed and validated to quantify liposomal pyridostigmine. The method was linear in ranges from 0.02 to 0.09 mg/mL. The accuracy of this method was determined intra- and inter-day; the results of coefficient of variation were of 1.73-2.72% and 0.32-2.32%, respectively. The accuracy ranged between 99.45% and 101.12%. The method has not changed by influence of liposomal matrix and demonstrated being able to quantify pyridostigmine in liposomes. Two liposomal multilamellar formulations were developed: a constituted by dystearoyl-phosphatidylcholine (DSPC) and cholesterol (CHOL) other by dioleil-phosphatidylcholine (DOPC) and CHOL. The encapsulation efficiency was determined as 23.4% and 15.4%, respectively. Analyses of size and release of pyridostigmine from the formulations were made and the results showed that the formulations are viable for future studies in vivo.

Relationship between clinical and pathological signs and severity of canine leishmaniasis.

Canine visceral leishmaniasis (CVL) is a zoonotic disease that presents variable clinical and laboratory aspects. The aims of this study were to identify the main biochemical/hematological status of dogs naturally infected with Leishmania (Leishmania) infantum and to associate theses parameters with clinical forms of CVL. Blood samples were analyzed from 51 dogs, 15 uninfected (control group) and 36 infected, which were classified clinically in three groups: asymptomatic (n=12), oligosymptomatic (n=12) and symptomatic (n=12). All the infected dogs showed lower albumin/globulin ratios (A-G ratio) than the limit of reference. The mean values of total protein, urea, α-globulin 2, globulin and A-G ratio of infected dogs were outside the reference interval and differed significantly from those of the controls. Anemia was detected only in groups that showed clinical signs of the disease, and a statistical analysis indicated a significantly higher frequency of lower eritrogram in these groups than in the asymptomatic group. In addition, a significant association was observed between anemia and the presence of the symptoms, with dogs displaying higher erythrogram values showing better clinical conditions. These results provide additional evidence that the clinical forms of CVL may reflect on the erythrogram status.

Relationship between clinical and pathological signs and severity of canine leishmaniasis / Relação entre sinais clínico-patológicos e gravidade da leishmaniose visceral canina

Canine visceral leishmaniasis (CVL) is a zoonotic disease that presents variable clinical and laboratory aspects. The aims of this study were to identify the main biochemical/hematological status of dogs naturally infected with Leishmania (Leishmania) infantum and to associate theses parameters with clinical forms of CVL. Blood samples were analyzed from 51 dogs, 15 uninfected (control group) and 36 infected, which were classified clinically in three groups: asymptomatic (n=12), oligosymptomatic (n=12) and symptomatic (n=12). All the infected dogs showed lower albumin/globulin ratios (A-G ratio) than the limit of reference. The mean values of total protein, urea, α-globulin 2, globulin and A-G ratio of infected dogs were outside the reference interval and differed significantly from those of the controls. Anemia was detected only in groups that showed clinical signs of the disease, and a statistical analysis indicated a significantly higher frequency of lower eritrogram in these groups than in the asymptomatic group. In addition, a significant association was observed between anemia and the presence of the symptoms, with dogs displaying higher erythrogram values showing better clinical conditions. These results provide additional evidence that the clinical forms of CVL may reflect on the erythrogram status.

A leishmaniose visceral canina (LVC) é uma zoonose com aspectos clínicos e laboratoriais variáveis. O objetivo deste trabalho foi identificar os principais achados hematológicos e bioquímicos em cães naturalmente infectados com Leishmania (Leishmania) infantum e associar esses parâmetros com as formas clínicas da LVC. Foram analisadas amostras sanguíneas provenientes de 51 cães, sendo 15 cães não infectados (grupo controle) e 36 infectados, os quais foram classificados clinicamente em três grupos: assintomáticos (n=12), oligossintomáticos (n=12) e sintomáticos (n=12). Todos os cães infectados apresentaram valores na relação albumina/globulina (A/G) abaixo do limite inferior de referência. Os valores médios de proteína total, uréia, α-2 globulina, globulina e A/G dos grupos de cães infectados permaneceram fora dos intervalos de referências e significativamente diferente quando comparados aos do grupo controle. Anemia foi registrada somente nos grupos de animais que manifestavam sinais clínicos da enfermidade, sendo que nas análises estatísticas constatou-se frequência significativamente maior de alterações no eritrograma quando comparados ao grupo assintomático. Associação significativa foi observada entre anemia e a presença de sinais clínicos, onde os cães com os maiores valores de eritrograma apresentavam a melhor condição clínica. Os resultados fornecem evidência adicional que as formas clínicas da LVC podem refletir no eritrograma.