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• W4313305412 endingPage "122572" @default.
• W4313305412 startingPage "122572" @default.
• W4313305412 abstract "Since pro-inflammatory macrophages take on a critical significance in the pathophysiology of rheumatoid arthritis (RA), the therapeutics to affect macrophages may receive distinct anti-RA effects. However, the therapeutic outcomes are still significantly impeded, which is primarily due to the insufficient drug delivery at the arthritic site. In this study, the macrophage-targeting and pH stimuli-responsive nano-polyelectrolyte complexes were designed for the efficient targeted delivery of triptolide (TP/PNPs) on the arthritic site. The anionic and cationic amphiphilic copolymers, i.e., hyaluronic acid-g-vitamin E succinate (HA-VE) and the quaternized poly (β-amino ester) (QPBAE-C18), were prepared and then characterized. The result indicated that TP/PNPs with the uniform particle size of ∼ 175 nm exhibited the high drug loading capacity and storage stability based on the polymeric charge interaction, in which DLC and DEE of TP/PNPs were obtained as 11.27 ± 0.44 % and 95.23 ± 2.34 %, respectively. Mediated by the ELVIS effect of NPs, CD44 receptor-mediated macrophage targeting, and pH-sensitive endo/lysosomal escape under the proton sponge effect, TP/PNPs exhibited the enhanced cellular internalization and cytotoxicity while mitigating the inflammation of LPS-activated RAW 264.7 cells. Even after 96-hour after administration, PNPs were preferentially accumulated in the inflammatory joints in a long term. It is noteworthy that after treatment for 14 days with 100 μg/kg of TP, TP/PNPs significantly facilitated arthritic symptom remission, protected cartilage, and mitigated inflammation of antigen-induced arthritis (AIA) rats, whereas the systematic side-effects of TP were reduced. In this study, an effective drug delivery strategy was proposed for the treatment of RA." @default.
• W4313305412 created "2023-01-06" @default.
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• W4313305412 date "2023-02-01" @default.
• W4313305412 modified "2023-10-01" @default.
• W4313305412 title "pH-sensitive nano-polyelectrolyte complexes with arthritic macrophage-targeting delivery of triptolide" @default.
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• W4313305412 doi "https://doi.org/10.1016/j.ijpharm.2022.122572" @default.
• W4313305412 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36592894" @default.
• W4313305412 hasPublicationYear "2023" @default.
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