Improved bioavailability of polydatin and its protective effect against cisplatin induced nephrotoxicity through self-assembled fucoidan and carboxymethyl chitosan delivery system.
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| Format: | Artículo científico |
| Language: | en |
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International journal of biological macromolecules
2025
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| _version_ | 1868266270315511808 |
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| author | Wang, Yinghan Xue, Pengyu Gao, Liang Wang, Xuefei Zhou, Shilin Wu, Xiaochen Guo, Chuanlong |
| author_facet | Wang, Yinghan Xue, Pengyu Gao, Liang Wang, Xuefei Zhou, Shilin Wu, Xiaochen Guo, Chuanlong Wang, Yinghan Xue, Pengyu Gao, Liang Wang, Xuefei Zhou, Shilin Wu, Xiaochen Guo, Chuanlong |
| collection | PubMed - marine biology |
| contents | Improved bioavailability of polydatin and its protective effect against cisplatin induced nephrotoxicity through self-assembled fucoidan and carboxymethyl chitosan delivery system. Wang, Yinghan Xue, Pengyu Gao, Liang Wang, Xuefei Zhou, Shilin Wu, Xiaochen Guo, Chuanlong Cisplatin Chitosan Polysaccharides Animals Humans Biological Availability Glucosides Stilbenes Acute Kidney Injury Cell Line DNA Damage Mice Male Kidney Protective Agents Reactive Oxygen Species Drug Carriers Nanoparticles Drug Delivery Systems Cisplatin induced acute kidney injury (AKI) is clinically prevalent, with a complex pathogenesis and a lack of effective therapeutic drugs. Polydatin (Po) has excellent biological activity, but its low solubility and bioavailability limit its application. In this study, fucoidan (Fu) and carboxymethyl chitosan (Cs) self-assembled into nanoparticles through electrostatic interactions/hydrogen bonding and loaded Po (Fu/Cs Po NPs). In vitro studies found that Fu/Cs Po NPs protected human renal tubular epithelial (HK-2) cells from cisplatin induced damage and accumulation of reactive oxygen species (ROS). Mechanistic studies showed that Fu/Cs Po NPs inhibited cisplatin induced DNA damage and activation of cyclic guanosine monophosphate synthase (cGAS) and intron gene stimulator (STING) pathways. In vivo studies showed that Fu/Cs Po NPs treatment alleviated cisplatin induced AKI symptoms, including elevated blood urea nitrogen (BUN) and serum creatinine (SCr), as well as pathological damage to kidney tissues. In vivo mechanism studies also showed that Fu/Cs Po NPs treatment inhibited cisplatin induced DNA damage and activation of the cGAS-STING pathway. The pharmacokinetic and tissue distribution results demonstrated that the Fu/Cs delivery system enhanced the bioavailability and kidney accumulation of Po in vivo. In summary, our study provided potential drugs for the treatment of cisplatin induced AKI. |
| format | Artículo científico |
| id | pubmed_39657878 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | International journal of biological macromolecules |
| record_format | pubmed |
| spellingShingle | Improved bioavailability of polydatin and its protective effect against cisplatin induced nephrotoxicity through self-assembled fucoidan and carboxymethyl chitosan delivery system. Wang, Yinghan Xue, Pengyu Gao, Liang Wang, Xuefei Zhou, Shilin Wu, Xiaochen Guo, Chuanlong Cisplatin Chitosan Polysaccharides Animals Humans Biological Availability Glucosides Stilbenes Acute Kidney Injury Cell Line DNA Damage Mice Male Kidney Protective Agents Reactive Oxygen Species Drug Carriers Nanoparticles Drug Delivery Systems Improved bioavailability of polydatin and its protective effect against cisplatin induced nephrotoxicity through self-assembled fucoidan and carboxymethyl chitosan delivery system. Wang, Yinghan Xue, Pengyu Gao, Liang Wang, Xuefei Zhou, Shilin Wu, Xiaochen Guo, Chuanlong Cisplatin Chitosan Polysaccharides Animals Humans Biological Availability Glucosides Stilbenes Acute Kidney Injury Cell Line DNA Damage Mice Male Kidney Protective Agents Reactive Oxygen Species Drug Carriers Nanoparticles Drug Delivery Systems Cisplatin induced acute kidney injury (AKI) is clinically prevalent, with a complex pathogenesis and a lack of effective therapeutic drugs. Polydatin (Po) has excellent biological activity, but its low solubility and bioavailability limit its application. In this study, fucoidan (Fu) and carboxymethyl chitosan (Cs) self-assembled into nanoparticles through electrostatic interactions/hydrogen bonding and loaded Po (Fu/Cs Po NPs). In vitro studies found that Fu/Cs Po NPs protected human renal tubular epithelial (HK-2) cells from cisplatin induced damage and accumulation of reactive oxygen species (ROS). Mechanistic studies showed that Fu/Cs Po NPs inhibited cisplatin induced DNA damage and activation of cyclic guanosine monophosphate synthase (cGAS) and intron gene stimulator (STING) pathways. In vivo studies showed that Fu/Cs Po NPs treatment alleviated cisplatin induced AKI symptoms, including elevated blood urea nitrogen (BUN) and serum creatinine (SCr), as well as pathological damage to kidney tissues. In vivo mechanism studies also showed that Fu/Cs Po NPs treatment inhibited cisplatin induced DNA damage and activation of the cGAS-STING pathway. The pharmacokinetic and tissue distribution results demonstrated that the Fu/Cs delivery system enhanced the bioavailability and kidney accumulation of Po in vivo. In summary, our study provided potential drugs for the treatment of cisplatin induced AKI. |
| title | Improved bioavailability of polydatin and its protective effect against cisplatin induced nephrotoxicity through self-assembled fucoidan and carboxymethyl chitosan delivery system. |
| topic | Cisplatin Chitosan Polysaccharides Animals Humans Biological Availability Glucosides Stilbenes Acute Kidney Injury Cell Line DNA Damage Mice Male Kidney Protective Agents Reactive Oxygen Species Drug Carriers Nanoparticles Drug Delivery Systems |
| url | https://pubmed.ncbi.nlm.nih.gov/39657878/ |