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Molecular insights into the formation of polymeric nanoassemblies of the anticancer peptide PEN-FFW

The peptide PEN-FFW has emerged as a candidate for hepatocellular carcinoma therapy, with selective efficacy and a favorable safety profile. Development of a suitable formulation has been hindered by its sensitivity to shear and limited physicochemical stability. In this work, we elucidated drug-exc...

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Hauptverfasser: Wang, Tianqi (VerfasserIn) , Lazareva, Polina A. (VerfasserIn) , Malinovskaya, Julia (VerfasserIn) , Panczyk, Tomasz (VerfasserIn) , Wen Hui, Joyce Ang (VerfasserIn) , Dhakal, Namrata (VerfasserIn) , Liu, Beijia (VerfasserIn) , Qin, Qiuhua (VerfasserIn) , Kovshova, Tatyana (VerfasserIn) , Sur, Somok (VerfasserIn) , Vadekhina, Veronika (VerfasserIn) , Ivanova, Anna V. (VerfasserIn) , Valikhov, Marat (VerfasserIn) , Reich, Gabriele (VerfasserIn) , Chen, Wenqian (VerfasserIn) , Gelperina, Svetlana (VerfasserIn) , Abakumov, Maxim A. (VerfasserIn) , Wacker, Matthias G. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 10 December 2025
In: Journal of controlled release
Year: 2025, Jahrgang: 388, Pages: 1-16
ISSN:1873-4995
DOI:10.1016/j.jconrel.2025.114364
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.jconrel.2025.114364
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0168365925009782
Volltext
Verfasserangaben:Tianqi Wang, Polina A. Lazareva, Julia Malinovskaya, Tomasz Panczyk, Joyce Ang Wen Hui, Namrata Dhakal, Beijia Liu, Qiuhua Qin, Tatyana Kovshova, Somok Sur, Veronika Vadekhina, Anna V. Ivanova, Marat Valikhov, Gabriele Reich, Wenqian Chen, Svetlana Gelperina, Maxim A. Abakumov, Matthias G. Wacker
Beschreibung
Zusammenfassung:The peptide PEN-FFW has emerged as a candidate for hepatocellular carcinoma therapy, with selective efficacy and a favorable safety profile. Development of a suitable formulation has been hindered by its sensitivity to shear and limited physicochemical stability. In this work, we elucidated drug-excipient interactions and exploited them to design a stable nanoassembly. PEN-FFW was encapsulated within a carboxymethyl cellulose-poly(lactide-co-glycolide) core, stabilized by polysorbate 80. Binding and structural features were confirmed by quartz crystal microbalance with dissipation (QCM-D), Fourier transform infrared (FTIR), and dynamic light scattering (DLS), while molecular modeling suggested the formation of a pocket accommodating the peptide within the core. A four-factor, three-level Box-Behnken design was applied to optimize process parameters, yielding a 50 % increase in encapsulation efficiency and enhanced storage stability, as determined by desirability function analysis. The optimized formulation exhibited superior cellular uptake and cytotoxicity in vitro, and in vivo studies in mice demonstrated significantly greater hepatic retention relative to the free peptide.
Beschreibung:Online verfügbar 28 October 2025, Version des Artikels 4 November 2025
Gesehen am 06.03.2026
This article is part of a Special issue entitled: ‘CRSingapore 2025’ published in Journal of Controlled Release
Beschreibung:Online Resource
ISSN:1873-4995
DOI:10.1016/j.jconrel.2025.114364

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