In this work, redox-sensitive polyurethane urea (PUU) based electrospun membranes have been exploited to chemically tether a pH-sensitive doxorubicin derivative achieved by linking a lipoyl hydrazide to the drug via a hydrazone linkage. First, the lipoyl-hydrazone-doxorubicin derivative labelled as LA-Hy-Doxo has been syn- thesized and characterized. Then, the molecule has been tethered, via a thiol-disulfide exchange reaction, to the redox-sensitive PUU (PolyCEGS) electrospun membrane. The redox-sensitive PolyCEGS PUU has been produced by using PCL-PEG-PCL polyol and glutathione-tetramethyl ester (GSSG-OMe)4 as a chain extender. The LA-Hy- Doxo tethered electrospun membrane has showed a dually controlled release triggered by acidic and reducing conditions, producing a significant cytotoxic effect in human breast cancer cell lines (MCF-7) which has validated the system for the post-surgical treatment of solid tumors to contrast recurrence
Salvatore Federico, A.M. (2022). Development of stimulus-sensitive electrospun membranes based on novel biodegradable segmented polyurethane as triggered delivery system for doxorubicin. BIOMATERIALS ADVANCES, 136, 1-13 [10.1016/j.bioadv.2022.212769].
Development of stimulus-sensitive electrospun membranes based on novel biodegradable segmented polyurethane as triggered delivery system for doxorubicin
Salvatore FedericoPrimo
;Annalisa MartoranaSecondo
;Giovanna Pitarresi;Fabio Salvatore Palumbo
;calogero Fiorica;Gaetano giammona
2022-05-01
Abstract
In this work, redox-sensitive polyurethane urea (PUU) based electrospun membranes have been exploited to chemically tether a pH-sensitive doxorubicin derivative achieved by linking a lipoyl hydrazide to the drug via a hydrazone linkage. First, the lipoyl-hydrazone-doxorubicin derivative labelled as LA-Hy-Doxo has been syn- thesized and characterized. Then, the molecule has been tethered, via a thiol-disulfide exchange reaction, to the redox-sensitive PUU (PolyCEGS) electrospun membrane. The redox-sensitive PolyCEGS PUU has been produced by using PCL-PEG-PCL polyol and glutathione-tetramethyl ester (GSSG-OMe)4 as a chain extender. The LA-Hy- Doxo tethered electrospun membrane has showed a dually controlled release triggered by acidic and reducing conditions, producing a significant cytotoxic effect in human breast cancer cell lines (MCF-7) which has validated the system for the post-surgical treatment of solid tumors to contrast recurrenceFile | Dimensione | Formato | |
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