A PEGylated Nanostructured Lipid Carrier for Enhanced Oral Delivery of Antibiotics.

Antimicrobial resistance is a major concern for public health throughout the world that severely restricts available treatments. In this context, methicillin-resistant Staphylococcus aureus (MRSA) is responsible for a high percentage of S. aureus infections and mortality. To overcome this challenge, nanoparticles are appropriate tools as drug carriers to improve the therapeutic efficacy and decrease the toxicity of drugs. In this study, a polyethylene glycol (PEG)ylated nanostructured lipid carrier (PEG-NLC) was synthesized to improve the oral delivery of trimethoprim/sulfamethoxazole (TMP/SMZ) for the treatment of MRSA skin infection in vitro and in vivo. The nanoformulation (PEG-TMP/SMZ-NLC) was synthesized with size and drug encapsulation efficiencies of 187 ± 9 nm and 93.3%, respectively, which could release the drugs in a controlled manner at intestinal pH. PEG-TMP/SMZ-NLC was found efficient in decreasing the drugs' toxicity by 2.4-fold in vitro. In addition, the intestinal permeability of TMP/SMZ was enhanced by 54%, and the antibacterial effects of the drugs were enhanced by 8-fold in vitro. The results of the stability study demonstrated that PEG-TMP/SMZ-NLC was stable for three months. In addition, the results demonstrated that PEG-TMP/SMZ-NLC after oral administration could decrease the drugs' side-effects such as renal and hepatic toxicity by ~5-fold in MRSA skin infection in Balb/c mice, while it could improve the antibacterial effects of TMP/SMZ by 3 orders of magnitude. Overall, the results of this study suggest that the application of PEGylated NLC nanoparticles is a promising approach to improving the oral delivery of TMP/SMZ for the treatment of MRSA skin infection.

Carboplatin Niosomal Nanoplatform for Potentiated Chemotherapy.

This study aimed to characterize a stable nano-niosome formulation, which could reduce the adverse effects of carboplatin (CB) and improve its therapeutic efficacy in the treatment of breast cancer. For this purpose, CB-loaded polyethylene glycol (PEG)ylated niosome nanoparticles (PEG-NS-CB) were synthesized using the reverse-phase evaporation method. PEG-NS-CB (226.0 ± 10.6 nm) could release CB in a controlled manner and, compared to CB and CB-loaded non-PEGylated niosome (NS-CB), caused higher cytotoxicity effects against mouse breast cancer 4T1 cells (IC50: 83.4, 26.6, and 22.5 µM for CB, NS-CB, and PEG-NS-CB, respectively). Also, PEG-NS-CB demonstrated higher stability, in which its profile of drug release, cytotoxicity, and LE% did not change significantly three months after preparation compared to those at the production time. In addition, the in vivo results demonstrated that PEG-NS-CB caused higher therapeutic (the number of alive mice: 12, 15, and 17 out of 20 in CB, NS-CB, and PEG-NS-CB receiver groups, respectively) and less toxicity effects (weight loss of 17, 12.5, and 10% in CB, NS-CB, and PEG-NS-CB receiver groups, respectively), compared to NS-CB and CB in breast cancer-bearing mice. Overall, the results of this study suggest that PEG-NS-CB could be a promising formulation for the treatment of breast cancer.

The immune response against Toxoplasma gondii in BALB/c mice induced by mannose-modified nanoliposome of excreted/secreted antigens.

This study aimed to compare the immune response against Toxoplasma gondii (T. gondii) in BALB/c mice induced by excreted/secreted (E/S) antigens and mannose-modified nanoliposome of E/S antigens. Here, E/S antigens and mannose-modified nanoliposome of E/S antigens were firstly prepared, and then BALB/c female inbred mice were separately immunized. In the next step, anti-E/S antigen antibodies and the relative expression levels of IL-10 and IL-12 mRNA were detected by ELISA and real-time PCR, respectively. After immunization, mice were intraperitoneally challenged with 102 tachyzoites of T. gondii, and the survival rate was recorded. The ELISA analysis showed significant differences between the levels of anti-E/S antigen antibodies in the mice immunized by E/S antigens and those immunized by mannose-modified nanoliposome of E/S antigens at days 7, 10, 20, 25, and 30 (P < 0.05). Real-time PCR analysis showed that the relative expression of IL-10 was significantly decreased during 20 days. Yet, the relative expression of IL-12 was significantly increased during 20 days (P < 0.05). In T. gondii challenge test, significant differences were found between the survival rates of mice immunized by E/S antigens and mice immunized by mannose-modified nanoliposome with E/S antigens. This project evidenced that mannose-modified nanoliposome of E/S antigens induced a more powerful immune response against T. gondii in BALB/c mice when compared with excreted/secreted antigens alone.

Serum levels of CC chemokine ligands in cutaneous leishmaniasis patients.

The crucial functions of chemokine/receptors in numerous parasitic infections, including leishmaniasis, are well documented. This study aimed to assess the serum levels of CC ligand (CCL) 2, CCL5, and CCL11 in cutaneous leishmaniasis (CL) patients. 64 patients, suffering from CL and 100 healthy people were selected, and their blood serum concentrations of CCL2, CCL5, and CCL11 were measured using enzyme-linked immunosorbent assay. The results demonstrated that while the mean serum levels of CCL5 and CCL11 increased significantly in CL patients, the mean serum levels of CCL2 decreased, compared to the control group. Despite the sufficient production of CCL5 and CCL11 in CL patients, they suffered from CCL2 deficiency, as the defense mechanism against parasitic infection. These findings suggest a mechanism that might partially explain the patients' susceptibility to persistent infection and their inability to clear the parasites.

Levels of Transforming Growth Factor-Beta After Immunization of Mice With in vivo prepared Toxoplasma gondii Excretory/Secretory Proteins.

BACKGROUND: Zoonotic parasite Toxoplasma gondii has a high prevalence in human populations. A suitable vaccine for animals can stop the transmission of infection between animal and human. OBJECTIVES: The aim of this study was to evaluate in vivo prepared excretory/secretory antigens (E/SA) as a potential candidate for immunization against the parasite and its effect on the production of transforming growth factor-beta (TGF-ß). MATERIALS AND METHODS: Toxoplasma gondii tachyzoites were inoculated in the peritoneal cavity of mice and E/SA was harvested and used in animal immunization with and without adjuvant. Serum levels of anti-E/SA antibodies and TGF-ß were measured in days 0, 3, 7, 14, 28 and 56 after immunization using ELISA technique. The measurements were statistically analyzed. RESULTS: Our results showed that the serum levels of anti-E/SA immunoglobulins significantly increased in all of the immunized groups. The differences of the serum levels of TGF-ß between the groups were statistically significant at days 28 and 56 after immunization with E/SA. CONCLUSIONS: Based on our study, in vivo prepared E/SA may be considered as a good candidate for animal immunization.

Interleukin-10 Serum Levels after Vaccination with In Vivo Prepared Toxoplasma gondii Excreted/Secreted Antigens.

OBJECTIVES: Toxoplasma gondii is a worldwide prevalent zoonotic parasite which causes toxoplasmosis. An appropriate vaccine for animals could interrupt the circle between animals and humans. Our previous study showed that excreted/secreted antigens (E/SA), derived from the peritoneum of mice infected with T. gondii tachyzoites could be considered as a good candidate for animal vaccination. Interleukin-10 (IL-10) inhibits proliferation of B and T lymphocytes and induces homeostasis in immune system responses. However, since IL-10 has also been shown to suppress the killing of T. gondii by human macrophages, the aim of this study was to evaluate IL-10 serum levels after vaccination with T. gondii E/SA prepared in vivo. METHODS: T. gondii tachyzoites were inoculated in the peritoneum of mice and harvested E/SA were used as a vaccine, with and without adjuvant, in T. gondii infected and un-infected mice. IL-10 serum levels were evaluated using the ELISA technique. RESULTS: The data showed that although serum levels of IL-10 were not changed at the early phases, they were elevated at the end phases of vaccination with T. gondii E/SA. CONCLUSION: Based on these and our previous results, it can be concluded that in vivo prepared T. gondii E/SA could be considered as a good candidate for animal vaccination.