Potent efficiency of the novel nitazoxanide-loaded nanostructured lipid carriers against experimental cyclosporiasis.

Cyclosporiasis is a ubiquitous infection caused by an obligate intracellular protozoan parasite known as Cyclospora cayetanensis (C. cayetanensis). The disease is characterized by severe diarrhea which may be regrettably fatal in immunosuppressed patients. The commercially available treatment options have either severe side effects or low efficiency. In the present study, the novel formula of nitazoxanide (NTZ)-loaded nanostructured lipid carriers (NLCs) was assessed for the first time for C. cayetanensis treatment in both immunocompetent and immunosuppressed mice in comparison to commercially available drugs (trimethoprim-sulfamethoxazole (TMP-SMX) and NTZ). Swiss Albino mice were orally infected by 104 sporulated oocysts. The experimental groups were treated with the gold standard TMP-SMX, NTZ, blank NLCs and NTZ-loaded NLCs. The results demonstrated that NTZ-loaded NLCs represented the highest significant parasite percent reduction of (>98% reduction) in both immunocompetent and immunosuppressed mice designating successful tissue penetration and avoiding recurrence of infection at the end of the study. Oocysts treated with NTZ-loaded NLCs demonstrated the most mutilated rapturing morphology via scanning electron microscope examination as well as representing the most profound improvement of the histopathological picture. In conclusion, NTZ-loaded NLCs exhibited the uppermost efficacy in the treatment of cyclosporiasis. The safe nature and the anti-parasitic effect of the novel formulation encourage its use as a powerful treatment for human cyclosporiasis.

Remarkable histopathological improvement of experimental toxoplasmosis after receiving spiramycin-chitosan nanoparticles formulation.

The present study investigated the anti-Toxoplasma effect of chitosan nanoparticles [CS NPs], spiramycin, spiramycin co-administered with metronidazole and spiramycin-CS NPs formulation on the parasite burden and histopathological changes in the liver, spleen and brain in experimentally infected mice. Seventy male Swiss albino mice were classified into seven equal groups: healthy control (I), infected untreated control (II), infected group receiving CS NPs (III), spiramycin administered infected group (IV), infected group receiving spiramycin-metronidazole (V), infected receiving 400 mg/kg spiramycin-CS NPs (VI) and infected treated with spiramycin-loaded CS NPs 100 mg/kg (VII). All groups were inoculated intraperitoneally with 2500 T. gondii tachyzoites RH strain except the healthy control group. All groups were sacrificed on the 8th day after infection. Density of the parasite and histopathological examination of the liver, spleen and brain of all treated mice revealed reduction in the mean tachyzoites count as well as decreased inflammation, congestion and necrosis within tissue sections. Spiramycin-loaded NPs displayed the highest significant reduction in the pathological insult tailed by spiramycin-metronidazole and CS NPs. In conclusion, spiramycin-loaded CS NPs showed a promising synergistic combination in the treatment of the histopathology caused by toxoplasmosis.

The powerful synergistic effect of spiramycin/propolis loaded chitosan/alginate nanoparticles on acute murine toxoplasmosis.

The novel formula of spiramycin/propolis loaded chitosan (CS)/alginate (Alg) nanoparticles (NPs) was assessed for Toxoplasma gondii (T. gondii) treatment in comparison with the commercially available spiramycin regarding tissue penetration and blood brain barrier (BBB) passage. Swiss Albino mice were inoculated intraperitoneally by 2500 tachyzoites of the virulent T. gondii RH strain. The experimental groups were treated with oral spiramycin, propolis, CS/Alg NPs, spiramycin loaded CS/Alg NPs, propolis loaded CS/Alg NPs, and spiramycin/propolis loaded CS/Alg NPs. The results demonstrated that spiramycin/propolis loaded CS/Alg NPs exerted the longest survival time with no mortality on the sacrifice day (8th) in addition to representing the highest significant parasite percent reduction of (≥96% reduction) in liver, spleen and brain designating successful tissue penetration and BBB passage. Tachyzoites treated with spiramycin/propolis loaded CS/Alg NPs demonstrated the most disfigured rapturing organism via scanning electron microscope examination along with representing an overall remarkable improvement of the histopathological pictures of liver, spleen and brain. In conclusion, spiramycin/propolis loaded CS/Alg NPs showed the uppermost efficacy in the treatment of acute murine toxoplasmosis. The safe nature and the anti-parasitic effect of each of CS, Alg, spiramycin and propolis encourage the synergistic use of spiramycin/propolis loaded CS/Alg NPs as a potent treatment for human toxoplasmosis.

A single oral dose of celecoxib-loaded solid lipid nanoparticles for treatment of different developmental stages of experimental schistosomiasis mansoni.

Schistosomiasis, a neglected tropical parasitic disease, is associated with severe pathology, mortality and economic loss. The treatment and control of schistosomiasis depends mainly on a single dose of praziquantel (PZQ). Drug repurposing and nanomedicine attract great attention to improve anti-schistosomal therapy. Previously, we reported that celecoxib (CELE), the non-steroidal anti-inflammatory drug, showed potent anti-schistosomal efficacy in an oral dose of 20 mg/kg/day for five days against different developmental stages of Schistosoma mansoni (S. mansoni) infection in mice. The aim of the current study was to shorten the duration of CELE treatment to reach an effective single oral dose against different developmental stages of S. mansoni infection using solid lipid nanoparticles (SLNs) as nano-carriers. The latter enhance the solubility, bioavailability and drug delivery and hence can decrease the frequency of administration which is of great clinical value. CELE-loaded SLNs showed good colloidal properties, high entrapment efficiency and drug loading, sustained biphasic release pattern with excellent storage stability. The used regimen was efficient against different developmental stages of S. mansoni infection with the most pronounced effect against the juvenile stage where the worm load, the hepatic egg count and the intestinal egg count were reduced by 86.39%, 91.45% and 90.11%, respectively. Meanwhile, when targeting the invasive and the adult stages, it induced reduction in the worm load by 73.55% and 78.22%, the hepatic egg count by 69.99% and 75.39% and the intestinal egg count by 77.57% and 79.89%, respectively. Additionally, CELE-loaded SLNs caused extensive tegumental damage of adult worms and marked improvement in the liver pathology.

Effect of celecoxib against different developmental stages of experimental Schistosoma mansoni infection.

Due to the high prevalence of schistosomiasis and the wide use of praziquantel solely for mass drug administration to control the disease, there is a great concern about the potential emergence of reduced susceptibility strains. This, together with the concern that praziquantel is ineffective against juvenile worms highlight the importance of developing an alternative anti-schistosomal drug. Using nonsteroidal anti-inflammatory drugs against schistosome infection is considerable. The present study evaluated the effect of oral administration of five days celecoxib regimen (20 mg/kg/day) against different developmental stages of Schistosoma mansoni infection. This regimen induced significant reduction in worm burden, tissue egg count, individual female fecundity and the mean percentage of immature and mature eggs with increased mean percentage of dead eggs. More importantly, celecoxib was more potent than praziquantel in all these parasitological parameters (except in the worm burden when given against the adult stage where the difference was statistically non-significant). Scanning and transmission electron microscopy of the adult worms revealed severe tegumental damage, laceration of the muscular layers and oedema of the syncytial layer. There was disruption of the testicular, ovarian and vitelline glandular tissues with signs of apoptosis and abnormalities of the spermatozoa and the oocytes. Additionally, celecoxib induced reduction in the number and the size of the hepatic granulomata and also amelioration of the hepatic tissue pathology.

Repurposing auranofin for treatment of Experimental Cerebral Toxoplasmosis.

PURPOSES: Evaluate the effect of auranofin on the early and late stages of chronic infection with Toxoplasma gondii avirulent ME49 strain. METHODS: Swiss albino mice were orally inoculated with 10 cysts of Toxoplasma gondii, and orally treated with auranofin or septazole in daily doses of 20 mg/kg or 100 mg /kg, respectively, for 30 days. Treatment began either on the same day of infection and mice were sacrificed at the 60th day postinfection or the treatment started after 60 days of infection and mice were sacrificed at the 90th day postinfection. RESULTS: Auranofin significantly reduced the brain cyst burden and inflammatory reaction at both stages of infection compared to the infected non-treated control. More remarkably, auranofin significant reduced the brain cyst burden in the late stage, while septazole failed. Hydrogen peroxide level was significantly increased in the brain homogenate of mice treated with auranofin only at the early stage of infection. Ultrastructral studies revealed that the anti-Toxoplasma effect of auranofin is achieved by changing the membrane permeability and inducing apoptosis. CONCLUSIONS: Thus, auranofin could be an alternative for the standard treatment regimen of toxoplasmosis and these results are considered another achievement for the drug against parasitic infection. Being a FDA-approved drug, it can be rapidly evaluated in clinical trials.