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Drug-loaded nanomicelles with ROS-responsive controlled release of carnosic acid for the treatment of ulcerative
Jie Zhang1, Ruilin Zhang2, Enlong Wang1
1Pingshan District People's Hospital of Shenzhen, Guangdong, China.
Abstract:
Conventional mode of administration has limited efficacy in the treatment of ulcerative colitis (UC). Drug-loaded nanomicelles with smart responsive improve the bioavailability of the loaded drug, thereby improving therapeutic effects in UC. Herein, drug-loaded nanomicelles (VTH@CA) were formed via the self-assembly of the reactive oxygen species (ROS)-responsive thioketal (TK) bridging hydrophilic and hydrophobic groups, in which carnosic acid (CA) was encapsulated in the core of micelles. VTH@CA showed a well-dispersed spherical structure with nanoscale dimensions. The designed nanomicelles demonstrated excellent antibacterial, antioxidant and biocompatibility activities. Cellular experiments also confirmed that VTH@CA could effectively alleviate the inflammatory response of LPS-activated macrophages. Moreover, hyaluronic acid (HA) as the hydrophilic end, had specifically targeted cluster of differentiation 44 receptor, and subsequently the TK bond responded to ROS for triggered release of CA. Compared to free CA administration, VTH@CA significantly alleviated histopathological features in the colon, reduced the expression of pro-inflammatory cytokines, and suppressed cellular apoptosis, demonstrating superior therapeutic efficacy. Therefore, VTH@CA can achieve on-demand drug release and offer a promising therapeutic drug-loaded platform for the treatment of intestinal tract diseases.
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