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Ivermectin (IVM) is one of the competitive treatments used for trichinellosis. However, several studies linked its efficacy with early diagnosis and administration to tackle the intestinal phase with limited activity being recorded against encysted larvae. The aim of this study was to employ niosomes for enhancing effectiveness of oral IVM against...
Citations
... The findings demonstrated an enhanced efficacy of the drug when delivered through the nanocarrier (Marslin et al., 2017). Elmehy et al. (2021) reported that niosomes enhanced the efficacy of oral Ivermectin against various stages of T. spiralis infection compared to nano-crystalline Ivermectin. Both niosomes and nano-crystals caused a significant decrease in adult and larval counts with superior activity of niosomal Ivermectin by reduction of inflammation in both jejunal and muscle homogenates. ...
... Both niosomes and nano-crystals caused a significant decrease in adult and larval counts with superior activity of niosomal Ivermectin by reduction of inflammation in both jejunal and muscle homogenates. Niosomal form efficacy exceeded the nanocrystalline form in the treatment of different phases of trichinellosis (Elmehy et al., 2021). ...
... The primary contributing factors to the pathology of T. spiralis are the mechanical injury induced by infection, inflammatory cells accumulation, and disruptions in the normal redox status [11]. The invasion of the host intestinal epithelium by infective larvae during the early stages leads to changes in the levels of pro-inflammatory cytokines and chemokines and alterations in the antioxidant capacity. ...
... The oxidant/antioxidant status is generally achieved through the equilibrium between the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as well as their elimination by antioxidants. Consequently, tissues frequently exhibit an augmented production of antioxidants in reaction to mild levels of oxidative stress [11]. ...
... Albendazole (ABZ) is the drug of choice in treating trichinellosis [3,17]. Despite its effectiveness, it is active against adult-stage and non-encysted muscle larvae only [11]. Moreover, its bioavailability is restricted because it is a poorly water-soluble and highly lipophilic drug with high reported resistance. ...
Purpose
Resistance and adverse consequences of albendazole (ABZ) in treating trichinellosis urged demand for secure and effective new drugs. The current study aimed to assess the effect of chitosan-coated lipid nano-combination with albendazole and miltefosine (MFS) in treating experimental murine trichinellosis and evaluating pathological and immunological changes of trichinellosis.
Materials and Methods
One hundred twenty Swiss albino mice were divided into six groups. Each group was subdivided into a and b subgroups based on the scarification time, which was 7- and 40-days post-infection (PI), respectively. The treatment efficacy was evaluated using parasitological, histopathological, serological (interleukin (IL)-12 and IL-4 serum levels), immunohistochemical (GATA3, glutathione peroxidase1 (GPX1) and caspase-3), and scanning electron microscopy (SEM) methods.
Results
The most effective drug was nanostructured lipid carriers (NLCs) loaded with ABZ (G5), which showed the most significant reduction in adults and larval count (100% and 92.39%, respectively). The greatest amelioration in histopathological changes was reported in G4 treated with MFS. GATA3 and caspase-3 were significantly reduced in all treated groups. GPX1 was significantly increased in G6 treated with MFS + NLCs. The highest degenerative effects on adults and larvae by SEM were documented in G6.
Conclusion
Loading ABZ or MFS on chitosan-coated NLCs enhanced their efficacy against trichinellosis. Although ABZ was better than MFS, their combination should be considered as MFS caused a significant reduction in the intensity of infection. Furthermore, MFS showed anti-inflammatory (↓GATA3) and antiapoptotic effects (↓caspase-3), especially in the muscular phase. Also, when loaded with NLCS, it showed an antioxidant effect (↑GPX1).
Graphical abstract
... In comparison with infected, untreated control mice at various stages, biochemical parameters in all treated mice showed highly significant differences, with niosomal IVM having a particularly strong influence. In addition, in this study, the effectiveness of niosomal IVM in treating various phases of trichinellosis outperformed that of nano-crystalline IVM (Elmehy et al., 2021). ...
Niosomes are drug delivery systems with widespread applications in pharmaceutical research and the cosmetic industry. Niosomes are vesicles of one or more bilayers made of non-ionic surfactants, cholesterol, and charge inducers. Because of their bilayer characteristics, similar to liposomes, niosomes can be loaded with lipophilic and hydrophilic cargos. Therefore, they are more stable and cheaper in preparation than liposomes. They can be classified into four categories according to their sizes and structures, namely small unilamellar vesicles (SUVs), large unilamellar vesicles (LUVs,), multilamellar vesicles (MLVs), and multivesicular vesicles (MVVs). There are many methods for niosome preparation, such as thin-film hydration, solvent injection, and heating method. The current study focuses on the preparation methods and pharmacological effects of niosomes loaded with natural and chemical anti-inflammatory compounds in kinds of literature during the past decade. We found that most research was carried out to load anti-inflammatory agents like non-steroidal anti-inflammatory drugs (NSAIDs) into niosome vesicles. The studies revealed that niosomes could improve anti-inflammatory agents' physicochemical properties, including solubility, cellular uptake, stability, encapsulation, drug release and liberation, efficiency, and oral bioavailability or topical absorption.
... In comparison with infected, untreated control mice at various stages, biochemical parameters in all treated mice showed highly significant differences, with niosomal IVM having a particularly strong influence. In addition, in this study, the effectiveness of niosomal IVM in treating various phases of trichinellosis outperformed that of nano-crystalline IVM (Elmehy et al., 2021). ...
Niosomes are drug delivery systems with widespread applications in pharmaceutical research and the cosmetic
industry. Niosomes are vesicles of one or more bilayers made of non-ionic surfactants, cholesterol, and charge
inducers. Because of their bilayer characteristics, similar to liposomes, niosomes can be loaded with lipophilic and
hydrophilic cargos. Therefore, they are more stable and cheaper in preparation than liposomes. They can be clas-
sified into four categories according to their sizes and structures, namely small unilamellar vesicles (SUVs), large
unilamellar vesicles (LUVs,), multilamellar vesicles (MLVs), and multivesicular vesicles (MVVs). There are
many methods for niosome preparation, such as thin-film hydration, solvent injection, and heating method. The
current study focuses on the preparation methods and pharmacological effects of niosomes loaded with natural
and chemical anti-inflammatory compounds in kinds of literature during the past decade. We found that most
research was carried out to load anti-inflammatory agents like non-steroidal anti-inflammatory drugs (NSAIDs)into niosome vesicles. The studies revealed that niosomes could improve anti-inflammatory agents' physicochem-
ical properties, including solubility, cellular uptake, stability, encapsulation, drug release and liberation, efficiency,
and oral bioavailability or topical absorption
... In the same context, Soliman et al. (2013) observed lower activity of antioxidant enzymes such as SOD and protein carbonyl in Trichinella-infected mice after IVM treatment. The same was reported by Elmehy et al. (2021), who noticed that treatment with IVM added to niosomes and nano-crystals resulted in a significant reduction in antioxidant enzymes activities as lactate dehydrogenase and glutathione-S-transferase at both phases of trichinellosis. Moreover, Othman et al. (2016) noticed that atorvastatin reduced the levels of SOD and pAMPK in intestinal and muscular tissue homogenates in T. spiralis-infected mice. ...
... 3.53 ± 0.47 P < 0.001* P < 0.001* 1.2 ± 0.1 P > 0.05 P < 0.001* 22.2 ± 0.76 P < 0.001* P < 0.001* A10 4 ± 0.2 P < 0.001* P < 0.001* 1.34 ± 0.05 P < 0.001* P < 0.001* 23.2 ± 3.01 P < 0.01* P < 0. Elmehy et al. 2021). Therefore, angiogenesis can be evaluated by estimating the level of VEGF gene expression besides measuring the MVD through immunohistochemical staining of specific endothelial cell markers such as CD31 (Rayia et al. 2022). ...
... Fadil et al. (2022) recorded that administration of IVM alone in experimental trichinellosis resulted in lower expression of VEGF mRNA and CD31-positive stained vessels. The same was recorded by Elmehy et al. (2021), who noticed that niosomal IVM and nanocrystalline IVM showed enhanced anti-angiogenic effect as the level of VEGF measured by ELISA was significantly decreased in tissues of Trichinella-infected mice. Othman et al. (2016) mentioned that atorvastatin revealed lower immunohistochemical expression of VEGF in the skeletal muscles of T. spiralis-infected mice. ...
Trichinellosis is one of the global food-borne parasitic diseases that can cause severe tissue damage. The traditionally used drugs for the treatment of trichinellosis have limited efficacy against the encysted larvae in the muscular phase of the disease. Therefore, this study aimed to evaluate the role of atorvastatin and mesenchymal stem cells combined with ivermectin against different phases of Trichinella in experimentally infected mice. A total of 120 male Swiss albino mice were divided into two major groups (n = 60 of each), intestinal and muscular phases. Then, each group was subdivided into 10 subgroups (n = 6); non-infected control, infected non-treated control, infected ivermectin treated, infected atorvastatin treated, infected mesenchymal stem cells treated, infected combined ivermectin and atorvastatin treated, infected combined mesenchymal stem cells and ivermectin treated, infected combined mesenchymal stem cells and atorvastatin treated, infected combined mesenchymal stem cells and a full dose of (ivermectin and atorvastatin) treated, and infected combined mesenchymal stem cells and half dose of (ivermectin and atorvastatin) treated. Mice were sacrificed at days 5 and 35 post-infection for the intestinal and muscular phases, respectively. The assessment was performed through many parameters, including counting the adult intestinal worms and muscular encysted larvae, besides histopathological examination of the underlying tissues. Moreover, a biochemical assay for the inflammatory and oxidative stress marker levels was conducted. In addition, levels of immunohistochemical CD31 and VEGF gene expression as markers of angiogenesis during the muscular phase were investigated. The combined mesenchymal stem cells and atorvastatin added to ivermectin showed the highest significant reduction in adult worms and encysted larvae counts, the most noticeable improvement of the histopathological changes, the most potent anti-inflammatory (lowest level of IL-17) and anti-angiogenic (lowest expression of CD31 and VEGF) activities, and also revealed the highly effective one to relieve the oxidative stress (lowest level of SOD, GSH, and lipid peroxidase enzymes). These observed outcomes indicate that adding mesenchymal stem cells and atorvastatin to ivermectin synergistically potentiates its therapeutic efficacy and provides a promising candidate against trichinellosis.
... Low infection intensity remained asymptomatic but, heavy one caused severe muscle pain and complications (Nassef et al, 2018). Trichinellosis led to risky inflammatory reactions in the heart, lungs, and CNS up to death (Elmehy et al, 2021). ...
... The later steps of the infection are associated with striated muscle damage, severe inflammation in the brain, heart, and lungs, and eventually death. The therapeutic potential of oral drugs such as ivermectin in infection early steps have been confirmed; nevertheless, the low bioavailability of these drugs has seriously challenged their efficacy in the more advanced phases of infection [161,162]. Consequently, in the present study, a niosomal drug delivery system was proposed to improve the therapeutic effects of ivermectin. They began their biochemical and histopathological studies after synthesizing niosome nanocarriers and ivermectin nanocrystalline. ...
... In addition, a significant reduction in encysted larvae and their capsule destruction was reported in the diaphragm muscle of mice exposed to ivermectinloaded niosomes. The superiority of the ivermectin niosomal form is related to the high potential of niosomes in increasing bioavailability and maintaining sustained, and controlled drug release with the optimal dose [161]. ...
Numerous disorders go untreated owing to a lack of a suitable drug delivery technology or an appropriate therapeutic moiety, particularly when toxicities and side effects are a major concern. Treatment options for microbiological infections are not fulfilled owing to significant adverse effects or extended therapeutic options. Advanced therapy options, such as active targeting, may be preferable to traditional ways of treating infectious diseases. Niosomes can be defined as microscopic lamellar molecules formed by a mixture of cholesterol, nonionic surfactants (alkyl or dialkyl polyglycerol ethers), and sometimes charge-inducing agents. These molecules comprise both hydrophilic and hydrophobic moieties of varying solubilities. In this review, several pathogenic microbes such as Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Plasmodium, Leishmania, and Candida spp. have been evaluated. Also, the development of a proper niosomal formulation for the required application was discussed. This review also reviews that an optimal formulation is dependent on several aspects, including the choice of nonionic surfactant, fabrication process, and fabrication parameters. Finally, this review will give information on the effectiveness of niosomes in treating acute microbial infections, the mechanism of action of niosomes in combating microbial pathogens, and the advantages of using niosomes over other treatment modalities.
... A decrease in inflammation in both jejunal and muscle homogenates further demonstrated the superiority of niosomes. Finally, niosomal IVM performed better than nano-crystalline IVM in treating various stages of trichinellosis (Elmehy et al., 2021). ...
The buildup of nonionic surfactants in the aqueous environment produces niosomes. The usage of niosomes is becoming increasingly frequent due to their sustainability, low cost of components and assembly, large-scale manufacture, and, finally, easy maintenance of the niosomes to the other. Because of their nonionic characteristics, niosomes play a critical role in medication delivery systems. Controlled release and targeted distribution of niosomes to treat cancer, infectious illnesses, and other disorders are one of their most important properties. Niosomes can also be injected by ocular and transdermal routes, which are less common than oral and parenteral administration. Using niosomes to manufacture biotechnology goods and novel vaccines is one of the most exciting research fields today. The molecular structure of niosomes, the physicochemical characteristics of nonionic surfactants in their formulation, the influence of external stimuli on niosomes, the many methods of niosomes administration, and their diverse therapeutic qualities are all explored in this study.
