Redox-Responsive Comparison of Diselenide and Disulfide Core-Cross-Linked Micelles for Drug Delivery Application

In this study, diselenide (Se–Se) and disulfide (S–S) redox-responsive core-cross-linked (CCL) micelles were synthesized using poly(ethylene oxide)<sub<2k</sub<-<i<b</i<-poly(furfuryl methacrylate)<sub<1.5k</sub< (PEO<sub<2k</sub<-<i<b</i<-PFMA<sub<1.5k</sub<), and their redox sensitivity was compared. A single electron transfer-living radical polymerization technique was used to prepare PEO<sub<2k</sub<-<i<b</i<-PFMA<sub<1.5k</sub< from FMA monomers and PEO<sub<2k</sub<-Br initiators. An anti-cancer drug, doxorubicin (DOX), was incorporated into PFMA hydrophobic parts of the polymeric micelles, which were then cross-linked with maleimide cross-linkers, 1,6-bis(maleimide) hexane, dithiobis(maleimido) ethane and diselenobis(maleimido) ethane via Diels–Alder reaction. Under physiological conditions, the structural stability of both S–S and Se–Se CCL micelles was maintained; however, treatments with 10 mM GSH induced redox-responsive de-cross-linking of S–S and Se–Se bonds. In contrast, the S–S bond was intact in the presence of 100 mM H<sub<2</sub<O<sub<2,</sub< while the Se–Se bond underwent de-crosslinking upon the treatment. DLS studies revealed that the size and PDI of (PEO<sub<2k</sub<-<i<b</i<-PFMA<sub<1.5k</sub<-Se)<sub<2</sub< micelles varied more significantly in response to changes in the redox environment than (PEO<sub<2k</sub<-<i<b</i<-PFMA<sub<1.5k</sub<-S)<sub<2</sub< micelles. In vitro release studies showed that the developed micelles had a lower drug release rate at pH 7.4, whereas a higher release was observed at pH 5.0 (tumor environment). The micelles were non-toxic against HEK-293 normal cells, which revealed that they could be safe for use. Nevertheless, DOX-loaded S–S/Se–Se CCL micelles exhibited potent cytotoxicity against BT-20 cancer cells. Based on these results, the (PEO<sub<2k</sub<-<i<b</i<-PFMA<sub<1.5k-</sub<Se)<sub<2</sub< micelles can be more sensitive drug carriers than (PEO<sub<2k</sub<-<i<b</i<-PFMA<sub<1.5k</sub<-S)<sub<2</sub< micelles..

Medienart:	E-Artikel

Erscheinungsjahr:	2023
Erschienen:	2023

Enthalten in:	Zur Gesamtaufnahme - volume:15
Enthalten in:	Pharmaceutics - 15(2023), 4, p 1159

Sprache:	Englisch

Beteiligte Personen:	Sonyabapu Yadav [VerfasserIn] Kalyan Ramesh [VerfasserIn] Obireddy Sreekanth Reddy [VerfasserIn] Viswanathan Karthika [VerfasserIn] Parveen Kumar [VerfasserIn] Sung-Han Jo [VerfasserIn] Seong II Yoo [VerfasserIn] Sang-Hyug Park [VerfasserIn] Kwon Taek Lim [VerfasserIn]

Links:	doi.org [kostenfrei] doaj.org [kostenfrei] www.mdpi.com [kostenfrei] Journal toc [kostenfrei]

Themen:	Core-cross-linked micelles Diels–Alder reaction Diselenide Disulfide Drug delivery Pharmacy and materia medica Redox-responsive

doi:	10.3390/pharmaceutics15041159

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	DOAJ089791878