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Bài báo - Tạp chí
(2021) Trang: 18
Tạp chí: Zoonoses international Symposium 2021, Germany, 13-15/10/2021
Liên kết:

Cryptosporidiosis is an intestinal disease, which occurs in a variety of hosts including animals and humans. Until now, there is no vaccine available for this disease. Nitazoxanide (NTZ) is the only FDA approved drug for cryptosporidiosis treatment in man, however its efficacy in immunocompromised people such as AIDS patients or malnourished children is limited and it is not licensed for animals. A major obstacle faced by drugs against intracellular pathogens is the delivery of the drug into the target compartment within the infected cell. In this study, we have investigated the potential of the cellpenetrating peptide octaarginine to increase the uptake of NTZ by cells and thereby to improve its efficacy. For this purpose, octaarginine (R8) was synthetically attached to NTZ and the resulting complex NTZ-R8 tested for the inhibition of Cryptosporidium growth in comparison to unmodified NTZ. The inhibitory properties of NTZ and NTZ-R8 were tested both in vitro using the human ileocecal adenocarcinoma (HCT-8) cell line as well as in vivo on the IFN-γ-knockout mouse model. We observed in vitro a distinct improvement of drug efficacy when NTZ was attached to octaarginine. Also, using the IFN-γ K/O mouse model for cryptosporidiosis we register a significant improvement of animal survival after 7 days of treatment with NTZ-R8 (2mg/kg BW) compared to NTZ (2mg/kg BW) alone (p < 0.05). However, mice treated with NTZ-R8 did not reduce the number of oocysts shedding. This pilot study results encourage the further study of modified compound with higher treated doses and evaluation octaarginine application as a vehicle for anticryptosporidial compounds to develop alternative treatment solutions against this infection

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