Novel carvedilol-loaded pro-phytomicelles: formulation, characterization and enhanced protective efficacy against acetaminophen-inducedliverinjury in mice
[Display omitted] •• CAR pro-phytomicelles could be fabricated with simple process.•• CAR pro-phytomicelles demonstrated excellent characteristics.•• CAR pro-phytomicelles demonstated strong treatment efficacies against liver injury.•• CAR pro-phytomicelles regulated HMGB1 signaling in liver. The wo...
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Veröffentlicht in: | International journal of pharmaceutics 2022-09, Vol.625, p.122127-122127, Article 122127 |
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Sprache: | eng |
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•• CAR pro-phytomicelles could be fabricated with simple process.•• CAR pro-phytomicelles demonstrated excellent characteristics.•• CAR pro-phytomicelles demonstated strong treatment efficacies against liver injury.•• CAR pro-phytomicelles regulated HMGB1 signaling in liver.
The work describes a novel, small-molecule phytochemicals as nanomaterials based pro-micelles (pro-phytomicelles) drug delivery system, for oral delivery of carvedilol (CAR). This novel nanoformulation of CAR, named CAR pro-phytomicelles, was prepared with rebaudioside A (RA) and dipotassium glycyrrhizinate (DG) as mixed nanomaterials. The formulation was optimized, leading to a 502-fold increase in solubility of CAR in water as a result of encapsulation within mixed phytomicelles based on DG and RA. CAR pro-phytomicelles samples could be instantly dissolved into aqueous media to formulate clear phytomicelle solutions with CAR encapsulation efficiency of 99.67 ± 0.02 %, and small micelle size of 15.62 ± 0.27 nm. CAR pro-phytomicelles exhibited good storage stability, rapid in vitro release in simulated intestinal fluid, and improved in vitro antioxidant activity. CAR pro-phytomicelles had good biocompatibility. Protective efficacy evaluation revealed that acetaminophen overdose could induce high mortality and severe liver injury in mice, while CAR pro-phytomicelle treatment exhibited significant protective effect against acetaminophen overdose. This protective efficacy was due to a mechanism that involved the regulation of high-mobility group box 1 and its signaling-related proinflammatory cytokines. These results show that pro-phytomicelles could provide a new concept and promising therapeutics as nanomedicines for improving the activities of CAR against acetaminophen-induced liver injury. |
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ISSN: | 0378-5173 1873-3476 |
DOI: | 10.1016/j.ijpharm.2022.122127 |