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.

Dexamethasone simulates the anticancer effect of nano-formulated paclitaxel in breast cancer cells.

Although the chemosensitizing effect of Dexamethasone (DEX) and its ability to increase the sensitivity of breast cancer cells to chemotherapy were previously reported, this study aimed to explore how far cotreatment of breast cancer cells with paclitaxel (PTX) and DEX mimics the anticancer effect of nanoformulated PTX. To establish this goal, PTX was nanoformulated with poly (lactic-co-glycolic acid) (PLGA) and the nanoparticles (PTX-NPs) were physically authenticated. Breast cancer cells (MCF-7) were treated with PTX or PTX-NPs in presence or absence of low concentration (10 nM) of DEX. Cells viability (assessed by MTT assay), apoptosis (assessed by flow cytometry) and the expression of PTX resistance gene (TRX1) and PTX metabolizing genes (CYP2C8 and CYP3A4) were investigated. The results showed that nanoformulated PTX was validated by nano-size assessment, increased the anionic surface charge and prober conjugation with the biodegradable carrier (PLGA), as indicated by the FTIR spectroscopy. Initially, the IC50 value of PTX was 19.3 µg/ml and cotreatment with DEX minimized it to 5.22 µg/ml, whereas PTX-NPs alone inhibited cell proliferation with IC50 6.67 µg/ml. Also, in presence of DEX, PTX-NPs further decreased the IC50 to 5 µg/ml. In parallel, DEX has increased the responsiveness of cells to PTX without potentiating its apoptotic effect. Moreover, the glucocorticoid (with PTX or PTX-NPs) downregulated TXR1 gene by 26% (P < 0.01) and 28.4% (P < 0.05) respectively. Similarly, the mRNA level of CYP3A4 significantly decreased in presence of DEX. The main PTX metabolizing gene CYP2C8, in contrast, was upregulated, especially in cells cotreated with PTX/DEX (P < 0.001). Conclusively, the study reports that cotreatment of breast cancer cells with submolar concentration of DEX acts as similar as the nanoformulated PTX, possibly through its modulatory effects on the expression of the main PTX metabolizing gene (CYP2C8) and downregulating Taxol resistance gene.

Effect of nanoparticles on the therapeutic efficacy of praziquantel against Schistosoma mansoni infection in murine models.

Praziquantel (PZQ) is the main treatment of Schistosomiasis mansoni. However, resistance to it was described. So, there is a necessity to develop novel drugs or to enhance the present drugs. This work aimed to assess the efficacy of PZQ alone and when loaded on liposomes in treatment of S. mansoni infection by parasitological and histopathological studies in experimental murine models. 112 male laboratories bred Swiss Albino mice were used in this work. They were divided into four groups: Group 1: control group; Group 2: infected then treated by PZQ (500 mg/kg) at 7, 30 and 45 days post infection; Group 3: infected then treated by liposome encapsulated PZQ (lip.PZQ) (500 mg/kg) at 7, 30 and 45 days post infection; Group 4: infected then treated by free liposomes at 7, 30 and 45 days post infection. The results showed that G3 caused the highest significant reduction of the total worm count, eggs/gram liver tissue and intestine (97.2%, 99.3%, 99.5%) respectively. Followed by G2 (85.1%, 97.6%, 89.8%) respectively. Regarding the histopathological studies, G3 showed the highest significant reduction in number and diameter of hepatic granuloma (97.6% and 98.1%), followed by G2 (77.2% and 75%) when compared to other groups. In conclusion, lip.PZQ is more effective than free PZQ from all aspects especially when administered 45 days PI.

Successful treatment of acute experimental toxoplasmosis by spiramycin-loaded chitosan nanoparticles.

Spiramycin-metronidazole and spiramycin-loaded chitosan (CS) nanoparticles (NPs) were tested in comparison with the current spiramycin treatment of T.gondii concerning tissue penetration and blood brain barrier (BBB) passage. Swiss Albino mice were inoculated intraperitoneally with 2500 T. gondii tachyzoites RH strain and were divided into experimental and control groups. The experimental groups orally received CS NPs, spiramycin, spiramycin-metronidazole, spiramycin-loaded CS NPs 400 mg/kg and spiramycin-loaded CS NPs 100 mg/kg. Drug efficacy was assessed by mice survival time, mortality rate, parasite load in different organs and morphological study of the tachyzoites movement by light microscope and the ultra-structure by SEM. The results revealed that the maximum survival time of more than 200 days with no mortality on the sacrifice day (8th) was observed in mice receiving spiramycin-loaded NPs. Spiramycin-loaded NPs showed the highest significant percent reduction of tachyzoites (about 90% reduction) in liver, spleen and brain as compared to the other used drugs denoting successful bypass of BBB. Light microscopy of the treated peritoneal tachyzoites showed sluggish tachyzoites movement while the NPs caused loss of their movement. SEM of the treated tachyzoites were more mutilated and some of them appeared rupturing in those receiving CS NPs and spiramycin-loaded NPs. In conclusion, spiramycin-loaded NPs showed the highest efficiency in the treatment of acute toxoplasmosis. The non-toxic nature and the anti-parasitic effect of both CS and spiramycin make the use of spiramycin-loaded CS NPs a potential material for treatment of human toxoplasmosis.

The effect of lopinavir/ritonavir and lopinavir/ritonavir loaded PLGA nanoparticles on experimental toxoplasmosis.

A marked reduction has been achieved in the incidence and clinical course of toxoplasmic encephalitis after the introduction of protease inhibitors within the treatment regimen of HIV (HIV-PIs). This work was undertaken to study for the first time, the efficacy of HIV-PIs, lopinavir/ritonavir (L/R), as a therapeutic agent in acute experimental toxoplasmosis. Lopinavir/ritonavir (L/R) were used in the same ratio present in aluvia, a known HIV-PIs drug used in the developing countries in the treatment regimens of AID's patient. Poly lactic-co-glycolic acid (PLGA) nanoparticles were used as a delivery system to L/R therapy. L/R alone or after its encapsulation on PLGA were given to Swiss strain albino mice that were infected with RH virulent toxoplasma strain. Both forms caused parasitological improvement in both mortality rate and parasite count. The higher efficacy was achieved by using L/R PLGA together with minimizing the effective dose. There was significant reduction in the parasite count in the peritoneal fluid and the liver. Parasite viability and infectivity were also significantly reduced. The anti-toxoplasma effect of the drug was attributed to the morphological distortion of the tachyzoites as evident by the ultrastructure examination and suppressed the egress of tachyzoites. L/R also induced changes that suggest apoptosis and autophagy of tachyzoites. The parasitophorous vacuole membrane was disrupted and vesiculated. The nanotubular networks inside the parasitophorous vacuole were disrupted. Therefore, the present work opens a new possible way for the approved HIV-PIs as an alternative treatment against acute toxoplasmosis. Furthermore, it increases the list of the opportunistic parasites that can be treated by this drug. The successful in vivo effect of HIV-PIs against Toxoplasma gondii suggests that this parasite may be a target in HIV treated patients, thus decrease the possibility of toxoplasmic encephalitis development.