Synthetic niclosamide-loaded controlled-release nanospheres with high solubility and stability exerting multiple effects against Clostridioides difficile
IntroductionNiclosamide (NIC) has significant potential as a clinical therapeutic agent for Clostridioides difficile infection (CDI); however, its strong hydrophobicity hampers its oral bioavailability, and its active effects against C. difficile remain unclear.MethodsNiclosamide-loaded controlled-r...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1617631/full |
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| author | Yulei Tai Yulei Tai Meng Zhang Yuning Han Hui Hu Hui Hu Shan Lin Fangya Zhai Menglun Tian Xiaojun Song Shuangshuang Wan Shuangshuang Wan Yu Chen Yu Chen Dazhi Jin Dazhi Jin Dazhi Jin |
| author_facet | Yulei Tai Yulei Tai Meng Zhang Yuning Han Hui Hu Hui Hu Shan Lin Fangya Zhai Menglun Tian Xiaojun Song Shuangshuang Wan Shuangshuang Wan Yu Chen Yu Chen Dazhi Jin Dazhi Jin Dazhi Jin |
| author_sort | Yulei Tai |
| collection | DOAJ |
| description | IntroductionNiclosamide (NIC) has significant potential as a clinical therapeutic agent for Clostridioides difficile infection (CDI); however, its strong hydrophobicity hampers its oral bioavailability, and its active effects against C. difficile remain unclear.MethodsNiclosamide-loaded controlled-release hyaluronic acid-modified poly (lactic-co-glycolic acid) naosphernes (NIC@PLGA-HAs) were synthesized using an oil-in-water emulsion technique and their effects on C. difficile cell growth, spore germination, biofilm formation, and NIC interaction sites with C. difficile toxin B (TcdB) were analyzed.ResultsNIC@PLGA-HAs exhibited enhanced solubility and stability, with a water contact angle on a hydrophilic surface of 65.1° and a zeta potential of 31.57 ± 2.08 mV, and pH-responsive (pH 7.4) controlled-release characteristics compared to free NIC. The NIC@PLGA-HAs killed C. difficile vegetative cells at a minimum inhibitory concentration (MIC) of 4 μg/mL. When C. difficile cells were treated with NIC@PLGA-HAs at the 1/4 MIC, spore germination and biofilm formation were significantly inhibited compared to those in untreated cells (P < 0.01). NIC was found to interact with the receptor-binding domain of TcdB at 24 amino acid sites via an enthalpy-driven reaction (enthalpy change, 36.21 kJ/mol and entropy change, 212.9 J⋅mol/K). In vivo experimental findings in Mongolian gerbils indicated that NIC@PLGA-HAs outperformed free NIC in reducing pathological damage, diarrhea severity, weight loss, and TcdB production and enhanced the survival rate.ConclusionThese findings presented the therapeutic potential of NIC@PLGA-HAs with high solubility and stability, which simultaneously exerted multiple biological activities against C. difficile. |
| format | Article |
| id | doaj-art-8eba5cef5a6c42d3948dab58fc4acab6 |
| institution | DOAJ |
| issn | 1664-302X |
| language | English |
| publishDate | 2025-07-01 |
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| series | Frontiers in Microbiology |
| spelling | doaj-art-8eba5cef5a6c42d3948dab58fc4acab62025-08-20T03:09:35ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-07-011610.3389/fmicb.2025.16176311617631Synthetic niclosamide-loaded controlled-release nanospheres with high solubility and stability exerting multiple effects against Clostridioides difficileYulei Tai0Yulei Tai1Meng Zhang2Yuning Han3Hui Hu4Hui Hu5Shan Lin6Fangya Zhai7Menglun Tian8Xiaojun Song9Shuangshuang Wan10Shuangshuang Wan11Yu Chen12Yu Chen13Dazhi Jin14Dazhi Jin15Dazhi Jin16School of Laboratory of Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, ChinaLaboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Hangzhou, Zhejiang, ChinaSchool of Laboratory of Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, ChinaSchool of Laboratory of Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, ChinaSchool of Laboratory of Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, ChinaLaboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Hangzhou, Zhejiang, ChinaSchool of Laboratory of Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, ChinaSchool of Laboratory of Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, ChinaSchool of Laboratory of Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, ChinaDepartment of clinical laboratory, Hangzhou Medical College, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou, Zhejiang, ChinaSchool of Laboratory of Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, ChinaLaboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Hangzhou, Zhejiang, ChinaSchool of Laboratory of Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, ChinaLaboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Hangzhou, Zhejiang, ChinaSchool of Laboratory of Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, ChinaLaboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Hangzhou, Zhejiang, ChinaDepartment of clinical laboratory, Hangzhou Medical College, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou, Zhejiang, ChinaIntroductionNiclosamide (NIC) has significant potential as a clinical therapeutic agent for Clostridioides difficile infection (CDI); however, its strong hydrophobicity hampers its oral bioavailability, and its active effects against C. difficile remain unclear.MethodsNiclosamide-loaded controlled-release hyaluronic acid-modified poly (lactic-co-glycolic acid) naosphernes (NIC@PLGA-HAs) were synthesized using an oil-in-water emulsion technique and their effects on C. difficile cell growth, spore germination, biofilm formation, and NIC interaction sites with C. difficile toxin B (TcdB) were analyzed.ResultsNIC@PLGA-HAs exhibited enhanced solubility and stability, with a water contact angle on a hydrophilic surface of 65.1° and a zeta potential of 31.57 ± 2.08 mV, and pH-responsive (pH 7.4) controlled-release characteristics compared to free NIC. The NIC@PLGA-HAs killed C. difficile vegetative cells at a minimum inhibitory concentration (MIC) of 4 μg/mL. When C. difficile cells were treated with NIC@PLGA-HAs at the 1/4 MIC, spore germination and biofilm formation were significantly inhibited compared to those in untreated cells (P < 0.01). NIC was found to interact with the receptor-binding domain of TcdB at 24 amino acid sites via an enthalpy-driven reaction (enthalpy change, 36.21 kJ/mol and entropy change, 212.9 J⋅mol/K). In vivo experimental findings in Mongolian gerbils indicated that NIC@PLGA-HAs outperformed free NIC in reducing pathological damage, diarrhea severity, weight loss, and TcdB production and enhanced the survival rate.ConclusionThese findings presented the therapeutic potential of NIC@PLGA-HAs with high solubility and stability, which simultaneously exerted multiple biological activities against C. difficile.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1617631/fullloaded controlled-release nanospheresNiclosamideClostridioides difficilespore germinationbiofilm formationmultiple effects |
| spellingShingle | Yulei Tai Yulei Tai Meng Zhang Yuning Han Hui Hu Hui Hu Shan Lin Fangya Zhai Menglun Tian Xiaojun Song Shuangshuang Wan Shuangshuang Wan Yu Chen Yu Chen Dazhi Jin Dazhi Jin Dazhi Jin Synthetic niclosamide-loaded controlled-release nanospheres with high solubility and stability exerting multiple effects against Clostridioides difficile Frontiers in Microbiology loaded controlled-release nanospheres Niclosamide Clostridioides difficile spore germination biofilm formation multiple effects |
| title | Synthetic niclosamide-loaded controlled-release nanospheres with high solubility and stability exerting multiple effects against Clostridioides difficile |
| title_full | Synthetic niclosamide-loaded controlled-release nanospheres with high solubility and stability exerting multiple effects against Clostridioides difficile |
| title_fullStr | Synthetic niclosamide-loaded controlled-release nanospheres with high solubility and stability exerting multiple effects against Clostridioides difficile |
| title_full_unstemmed | Synthetic niclosamide-loaded controlled-release nanospheres with high solubility and stability exerting multiple effects against Clostridioides difficile |
| title_short | Synthetic niclosamide-loaded controlled-release nanospheres with high solubility and stability exerting multiple effects against Clostridioides difficile |
| title_sort | synthetic niclosamide loaded controlled release nanospheres with high solubility and stability exerting multiple effects against clostridioides difficile |
| topic | loaded controlled-release nanospheres Niclosamide Clostridioides difficile spore germination biofilm formation multiple effects |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1617631/full |
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