TY - JOUR
T1 - Enzyme-Responsive Nanoparticles for Dexamethasone Targeted Delivery to Treat Inflammation in Diabetes
AU - Schiffmann, Nathan
AU - Liang, Yifei
AU - Nemcovsky, Carlos E.
AU - Almogy, Michal
AU - Halperin-Sternfeld, Michal
AU - Gianneschi, Nathan C.
AU - Adler-Abramovich, Lihi
AU - Rosen, Eyal
N1 - Publisher Copyright:
© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.
PY - 2023/11/10
Y1 - 2023/11/10
N2 - Diabetes is a global epidemic accompanied by impaired wound healing and increased risk of persistent infections and resistance to standard treatments. Therefore, there is an immense need to develop novel methods to specifically target therapeutics to affected tissues and improve treatment efficacy. This study aims to use enzyme-responsive nanoparticles for the targeted delivery of an anti-inflammatory drug, dexamethasone, to treat inflammation in diabetes. These nanoparticles are assembled from fluorescently-labeled, dexamethasone-loaded peptide-polymer amphiphiles. The nanoparticles are injected in vivo, adjacent to labeled collagen membranes sub-periosteally implanted on the calvaria of diabetic rats. Following their implantation, collagen membrane resorption is linked to inflammation, especially in hyperglycemic individuals. The nanoparticles show strong and prolonged accumulation in inflamed tissue after undergoing a morphological switch into microscale aggregates. Significantly higher remaining collagen membrane area and less inflammatory cell infiltration are observed in responsive nanoparticles-treated rats, compared to control groups injected with free dexamethasone and non-responsive nanoparticles. These factors indicate improved therapeutic efficacy in inflammation reduction. These results demonstrate the potential use of enzyme-responsive nanoparticles as targeted delivery vehicles for the treatment of diabetic and other inflammatory wounds.
AB - Diabetes is a global epidemic accompanied by impaired wound healing and increased risk of persistent infections and resistance to standard treatments. Therefore, there is an immense need to develop novel methods to specifically target therapeutics to affected tissues and improve treatment efficacy. This study aims to use enzyme-responsive nanoparticles for the targeted delivery of an anti-inflammatory drug, dexamethasone, to treat inflammation in diabetes. These nanoparticles are assembled from fluorescently-labeled, dexamethasone-loaded peptide-polymer amphiphiles. The nanoparticles are injected in vivo, adjacent to labeled collagen membranes sub-periosteally implanted on the calvaria of diabetic rats. Following their implantation, collagen membrane resorption is linked to inflammation, especially in hyperglycemic individuals. The nanoparticles show strong and prolonged accumulation in inflamed tissue after undergoing a morphological switch into microscale aggregates. Significantly higher remaining collagen membrane area and less inflammatory cell infiltration are observed in responsive nanoparticles-treated rats, compared to control groups injected with free dexamethasone and non-responsive nanoparticles. These factors indicate improved therapeutic efficacy in inflammation reduction. These results demonstrate the potential use of enzyme-responsive nanoparticles as targeted delivery vehicles for the treatment of diabetic and other inflammatory wounds.
KW - diabetes
KW - drug delivery
KW - inflammation
KW - nanomaterials
KW - polymers
UR - http://www.scopus.com/inward/record.url?scp=85168561582&partnerID=8YFLogxK
U2 - 10.1002/adhm.202301053
DO - 10.1002/adhm.202301053
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 37498238
AN - SCOPUS:85168561582
SN - 2192-2640
VL - 12
JO - Advanced healthcare materials
JF - Advanced healthcare materials
IS - 28
M1 - 2301053
ER -
