Radwan, A., N. M. El-Lakkany, S. William, G. S. El-Feky, M. Y. Al-Shorbagy, S. Saleh, and S. Botros, "A novel praziquantel solid lipid nanoparticle formulation shows enhanced bioavailability and antischistosomal efficacy against murine S. mansoni infection.", Parasites & vectors, vol. 12, issue 1, pp. 304, 2019. Abstractsamira.pdf

BACKGROUND: Schistosomiasis is responsible for a considerable global disease burden. This work aimed to improve the therapeutic outcome of the only available antischistosomal drug worldwide, praziquantel (PZQ), by incorporating it into a novel carrier, "solid lipid nanoparticles (SLNs)", to enhance its solubility, bioavailability and efficacy. A simple, cost-effective method was used to prepare SLN-PZQ.

RESULTS: Compared to market PZQ (M-PZQ), SLN-PZQ was more bioavailable, as denoted by higher serum concentrations in both normal and infected mice where elevated K, AUC, C, and t with a decrease in k were demonstrated. The AUC for SLN-PZQ in normal and Schistosoma mansoni-infected groups was almost nine- and eight-fold higher, respectively, than that for M-PZQ in corresponding groups. In normal and S. mansoni-infected mice, SLN-PZQ was detectable in serum at 24 h, while M-PZQ completely vanished 8 h post-treatment. Additionally, enhanced absorption with extended residence time was recorded for SLN-PZQ. Compared to M-PZQ, SLN-PZQ revealed superior antischistosomal activity coupled with enhanced bioavailability in all treated groups where higher percentages of worm reduction were recorded with all dosages tested. This effect was especially evident at the lower dose levels. The ED of SLN-PZQ was 5.29-fold lower than that of M-PZQ, with a significantly higher reduction in both the hepatic and intestinal tissue egg loads of all treated groups and almost complete disappearance of immature deposited eggs (clearly evident at the low dose levels).

CONCLUSIONS: SLN-PZQ demonstrated enhanced PZQ bioavailability and antischistosomal efficacy with a safe profile despite the prolonged residence in the systemic circulation.

Yehiaa, R., S. Saleh, H. E. Abharc, A. S. Saadd, and M. Schaalan, "L-Carnosine protects against Oxaliplatin-induced peripheral neuropathy in colorectal cancer patients: A perspective on targeting Nrf-2 and NF-κB pathways", Toxicology and Applied Pharmacology, vol. 365, pp. 41-50, 2019. l_carnosine_feb_2019.pdf
El-Lakkany, N. M., W. H. El-Maadawy, S. S. H. el-Din, S. Saleh, M. M. Safar, S. M. E, S. H. Mohamed, S. S. Botros, Z. Demerdash, and O. A. Hammam, "Antifibrotic effects of gallic acid on hepatic stellate cells: In vitro and in vivo mechanistic study", Journal of Traditional and Complementary Medicine, vol. 9, pp. 45-53, 2019. gallic_on_stellate_cells__2019.pdf
Gamal-Eldeen, A. M., D. Moustafa, S. M. El-Daly, M. A. M. Abo-Zeid, S. Saleh, M. Khoobchandani, K. Katti, R. Shukla, and K. V. Katti, "Gum Arabic-encapsulated gold nanoparticles for a non-invasive photothermal ablation of lung tumor in mice.", Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, vol. 89, pp. 1045-1054, 2017 May. Abstract

BACKGROUND: In our previous work, we have extensively evaluated the physiochemical characteristics of Gum Arabic-encapsulated gold nanoparticles (GA-AuNPs; 15-18nm) and reported their effectiveness in stopping the tumor initiation via inhibiting the pre-neoplastic lesions in liver.

OBJECTIVE: The rationale of this study is to detect the efficiency of using GA-AuNPs in photothermal application as a non-invasive technique against lung tumor. We investigated the cytotoxicity of GA-AuNPs on A549 cells, and then studied their apoptotic, anti-inflammatory, lipid peroxidation and anti-neovascular effect in in vivo model using a chemically-induced lung cancer in mice. The histopathological changes due to GA-AuNPs were investigated.

RESULTS: In the presence of laser irradiation, GA-AuNPs had a considerable cytotoxicity against A549 cells. The treatment of lung tumor-bearing mice with GA-AuNPs followed by laser exposure enhanced the apoptotic pathway and this was obvious from the histopathological investigations and the elevations in cytochrome-c, death receptor 5 and the subsequent upregulation of caspase-3, we also reported a significant reduction in the levels of the inflammatory mediator TNF-α and the angiogenesis inducer VEGF. An induction of lipid peroxidation was also reported upon treatment with either GA or GA-AuNPs.

CONCLUSION: GA-AuNPs showed no cytotoxicity in the absence of light, however the combination of GA-AuNPs with laser induced cell death in lung tumor tissues with a reduction in the inflammation and angiogenesis together with an elevation in lipid peroxidation, suggesting the potential use of these functionalized nanoparticles as a promising photothermal non-invasive treatment modality.

Gamal-Eldeen, A. M., D. Moustafa, S. M. El-Daly, E. A. El-Hussieny, S. Saleh, M. Khoobchandani, K. L. Bacon, S. Gupta, K. Katti, R. Shukla, et al., "Photothermal therapy mediated by gum Arabic-conjugated gold nanoparticles suppresses liver preneoplastic lesions in mice.", Journal of photochemistry and photobiology. B, Biology, vol. 163, pp. 47-56, 2016 Oct. Abstract

This study validates the utility of Gum Arabic-conjugated gold nanoparticles (GA-AuNPs) and laser to induce photothermal inhibition of hepatocarcinogenesis, via employing a diethylnitrosamine (DEN)-mediated hepatocellular carcinoma model. This work included both of in vitro and in vivo studies; to investigate the GA-AuNPs cytotoxicity and phototoxicity in hepatic cell line; to delineate the GA-AuNPs therapeutic efficiency in DEN-induced preneoplastic lesions (PNLs) in the liver of Balb-C mice. The therapeutic effects of GA-AuNPs on the mediators of apoptosis, inflammation, and tumor initiation, as well as the histopathological changes in preneoplastic liver have been investigated. Our results infer that GA-AuNPs in combination with laser irradiation led to a significant reduction in the cell viability and in histone deacetylase activity in hepatocarcinoma HepG2 cells. In chemically-induced PNLs mice model our results have demonstrated that GA-AuNPs, with or without laser irradiation, induced cancer cell apoptosis through the activation of death receptors DR5 and caspase-3 and inhibited both of the PNLs incidence and the initiation marker (placental glutathione S-transferase; GST-P). The laser-stimulated GA-AuNPs significantly reduced the tumor necrosis factor-α levels. In summary, GA-AuNPs with laser treatment inhibited liver PNLs via the induction of the extrinsic apoptosis pathway and the inhibition of inflammation.

Gamal-Eldeen, A. M., D. Moustafa, S. M. El-Daly, E. A. El-Hussieny, S. Saleh, M. Khoobchandani, K. L. Bacon, S. Gupta, K. Katti, R. Shukla, et al., "Photothermal therapy mediated by gum Arabic-conjugated gold nanoparticles suppresses liver preneoplastic lesions in mice.", Journal of photochemistry and photobiology. B, Biology, vol. 163, pp. 47-56, 2016 Oct. Abstract

This study validates the utility of Gum Arabic-conjugated gold nanoparticles (GA-AuNPs) and laser to induce photothermal inhibition of hepatocarcinogenesis, via employing a diethylnitrosamine (DEN)-mediated hepatocellular carcinoma model. This work included both of in vitro and in vivo studies; to investigate the GA-AuNPs cytotoxicity and phototoxicity in hepatic cell line; to delineate the GA-AuNPs therapeutic efficiency in DEN-induced preneoplastic lesions (PNLs) in the liver of Balb-C mice. The therapeutic effects of GA-AuNPs on the mediators of apoptosis, inflammation, and tumor initiation, as well as the histopathological changes in preneoplastic liver have been investigated. Our results infer that GA-AuNPs in combination with laser irradiation led to a significant reduction in the cell viability and in histone deacetylase activity in hepatocarcinoma HepG2 cells. In chemically-induced PNLs mice model our results have demonstrated that GA-AuNPs, with or without laser irradiation, induced cancer cell apoptosis through the activation of death receptors DR5 and caspase-3 and inhibited both of the PNLs incidence and the initiation marker (placental glutathione S-transferase; GST-P). The laser-stimulated GA-AuNPs significantly reduced the tumor necrosis factor-α levels. In summary, GA-AuNPs with laser treatment inhibited liver PNLs via the induction of the extrinsic apoptosis pathway and the inhibition of inflammation.

Saleh, S., N. El-Maraghy, E. Reda, and W. Barakat, "Modulation of Diabetes and Dyslipidemia in Diabetic Insulin-Resistant Rats by Mangiferin: Role of Adiponectin and TNF-α ", Annals of the Brazilian Academy of Sciences , vol. 86, issue 4, pp. 1935-1947, 2014. mangiferin_paper_2014.pdf
Zakaria, S., A. M. Gamal-Eldeen, S. M. El-Daly, and S. Salehe, "Synergistic apoptotic effect of Doxil® and aminolevulinic acid-based photodynamic therapy on human breast adenocarcinoma cells", Photodiagnosis and Photodynamic Therapy, vol. 11, pp. 227—238, 2014.
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