Oral administration of encapsulated bovine lactoferrin protein nanocapsules against intracellular parasite Toxoplasma gondii

Abstract

Toxoplasma gondii is a deadly intracellular parasite known to reside in every nucleated cell and known to cause severe complications in immunocompromised host. Standard drugs are cost effective and cause side effects, therefore, there is a necessity for a new drug molecule with immunomodulatory potential. Lactoferrin (Lf) is a natural milk protein, which has shown antimicrobial properties in its nanoformulation using alginate chitosan calcium phosphate bovine lactoferrin nanocapsules (AEC-CCo-CP-bLf-NCs). The present study was aimed to analyze and compare the effect of bovine Lf (bLf) in its native as well as nanoformulation (AEC-CCo-CP-bLf-NC) against coccidian parasite T. gondii. In vitro analysis has shown a significant increase in nitric oxide production and low parasitemia in in vitro cell culture model. In vivo BALB/c mice model have been used to develop human toxoplasmosis model. After treatment with NCs it has substantially increased the bioavailability of the protein and showed comparatively increased levels of reactive oxygen species, nitric oxide production, and Th1 cytokine which helped in parasite clearance. The mechanism of action of NCs has been clarified by immunoreactivity analysis, which showed accumulation of Lf in macrophages of various visceral organs, which is the site of parasite multiplication. Effect of NCs has significantly decreased ( P <0.05) the parasite load in various organs and helped survival of mice till day 25 postinfection. Fe metabolism inside the mice has been found to be maintained even after administration of mono form of Lf, this indicates novelty of Lf protein. From the present study we concluded that nanoformulation did not reduce the therapeutic potential of Lf protein; however, nanoformulation has enhanced the stability of the protein and shown anti-toxoplasmal activity. Our study presents for the first time nanoformulation of Lf protein against Toxoplasma , which has advantages over the standard drug therapy without any side effects.

Role of Nanotechnology in Treating of Toxoplasma Gondii

“…Sulfadiazine and pyrimethamine are the two most frequently prescribed medications for treating human toxoplasmosis, and both of them have serious adverse effects that include allergy, and complications with the kidneys and liver (Abou-El-Naga et al 2017). Several antibiotics and anti-malarial medications have also been used, but they can also have harmful impact (Anand et al 2015). By changing their pharmacokinetics, the distinct physicochemical properties of nanoparticles can be used to enhance drug delivery.…”

“…By changing their pharmacokinetics, the distinct physicochemical properties of nanoparticles can be used to enhance drug delivery. According to Anand et al (2015), this may lead to slow delivery of drugs, improved target specificity, increased efficacy, and a decrease in side effects. Using nanotechnology-based methods, drugs that are toxic, poorly soluble, or easily degraded in the gastrointestinal tract can be administered to the body for more effective treatment at lower doses.…”

Lactoferrin: A Glycoprotein Involved in Immunomodulation, Anticancer, and Antimicrobial Processes

“…On the other hand, Lf from different species has been nanoencapsulated to test its effectiveness against various parasite species. This treatment has been successful against Plasmodium berghei and Toxoplasma gondii [ 136 , 137 ].…”

Lactoferrin in the Battle against Intestinal Parasites: A Review

“…Lf also has shown antimicrobial properties in its nanoformulation using alginate chitosan calcium phosphate bLf nanocapsules (AEC-CCo-CP-bLf-NCs). Anand et al [152] analyzed and compared the effect of bLf in its native as well as nanoformulation AEC-CCo-CP-bLf-NC against coccidian parasite T. gondii. The J7741 macrophage cell line culture model showed a significant increase in NO production and low parasitemia.…”