posted on 2021-11-18, 15:05authored byZhicheng Le, Zepeng He, Hong Liu, Lixin Liu, Zhijia Liu, Yongming Chen
The
local treatment of inflammatory bowel disease (IBD) by enzyme
therapeutics is challenging owing to hostile environments in the gastrointestinal
tract, leading to the hydrolysis and enzymatic degradation of labile
proteins. In this study, safe and efficient local drug delivery systems
were developed by antioxidant superoxide dismutase (SOD) sequestered
within lipid–polymer hybrid nanoparticles through sequential
self-assembly processes. Interestingly, we found that the sequestered
SOD exhibited long-term enzymatic stability and comparable biological
activity to the enzymes in the native form, probably owing to particle
encapsulation providing a physical barrier to prevent the enzymolysis
of proteins. We demonstrated that nanoparticle-based local drug delivery
systems showed excellent mucus-penetrating ability and inflammation-targeting
properties, owing to the particle surface with a poly(ethylene glycol)
(PEG) coating and folate functionalization, thus improving mucosal
retention time and drug delivery efficiency within the colorectal
region. Furthermore, SOD-containing lipid–polymer hybrid nanoparticles
could effectively mitigate inflammatory responses by regulating the
secretion of inflammation-associated cytokines, thus increasing therapeutic
outcomes in colitis mice through intrarectal administration. The findings
indicated that antioxidant enzymes sequestered within lipid–polymer
hybrid nanoparticles might be potential enzyme therapeutics for the
local treatment of some inflammatory diseases in the near future.