PMID- 32252000 OWN - NLM STAT- MEDLINE DCOM- 20210111 LR - 20210111 IS - 1873-4367 (Electronic) IS - 0927-7765 (Linking) VI - 191 DP - 2020 Jul TI - Delivery of benzoylaconitine using biodegradable nanoparticles to suppress inflammation via regulating NF-kappaB signaling. PG - 110980 LID - S0927-7765(20)30210-1 [pii] LID - 10.1016/j.colsurfb.2020.110980 [doi] AB - Rheumatoid arthritis (RA) is a kind of systemic autoimmune disease, and patients with RA usually suffer serious pain, resulting in low quality of life. The development of drug delivery systems (DDSs) provides a valid approach for RA therapy via inhibiting the secretion of inflammatory cytokines from macrophages. As a prevailing drug nanocarrier with distinctive superiority, polymeric nanoparticles (NPs) have attracted much attention in recent years. However, low biocompatibility and limited exploitation of drug with high efficiency are still the main challenges in RA treatment. To overcome the limitations, we prepared a biocompatible copolymer methoxy-poly(ethylene glycol)-poly(lactide-co-glycolide) (mPEG-PLGA). Moreover, benzoylaconitine (BAC) with superior anti-inflammatory effect was selected as model drug. It was isolated from Aconitum kusnezoffii Reichb and encapsulated into mPEG-PLGA NPs (NP/BAC) to increase the bioavailablity of BAC. The NPs exhibited high cytocompatibility for activated macrophages and well compatibility with red blood cells. Furthermore, the anti-inflammatory property of NP/BAC was testified by substantially inhibiting secretion of pro-inflammatory cytokines. The TNF-alpha and IL-1beta cytokines of NP/BAC group reduced 70 % and 66 % compared with that of activated macrophages. Especially, NP/BAC reduced the overexpression of NF-kappaB p65 to inhibit NF-kappaB signaling pathway, which was a critical regulator of inflammatory responses. NP/BAC also showed efficient in vivo anti-inflammatory effect with high ear (69.8 %) and paw (87.1 %) swelling suppressing rate. These results revealed the anti-inflammatory mechanism of NP/BAC and proved it was a suitable DDS to suppress inflammation, providing a promising strategy for RA therapy and research of Aconitum kusnezoffii Reichb. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Gai, Weiwei AU - Gai W AD - Nano Innovation Institute, Inner Mongolia Key Laboratory of Carbon Nanomaterials, College of Chemistry and Materials Science, Inner Mongolia University for Nationalities, Tongliao, 028000, China. FAU - Hao, Xuefang AU - Hao X AD - Nano Innovation Institute, Inner Mongolia Key Laboratory of Carbon Nanomaterials, College of Chemistry and Materials Science, Inner Mongolia University for Nationalities, Tongliao, 028000, China. Electronic address: hxf15175374404@126.com. FAU - Zhao, Jiadi AU - Zhao J AD - Nano Innovation Institute, Inner Mongolia Key Laboratory of Carbon Nanomaterials, College of Chemistry and Materials Science, Inner Mongolia University for Nationalities, Tongliao, 028000, China. FAU - Wang, Lina AU - Wang L AD - Nano Innovation Institute, Inner Mongolia Key Laboratory of Carbon Nanomaterials, College of Chemistry and Materials Science, Inner Mongolia University for Nationalities, Tongliao, 028000, China. FAU - Liu, Jinghai AU - Liu J AD - Nano Innovation Institute, Inner Mongolia Key Laboratory of Carbon Nanomaterials, College of Chemistry and Materials Science, Inner Mongolia University for Nationalities, Tongliao, 028000, China. FAU - Jiang, Haixia AU - Jiang H AD - Analysis and Testing Center of Inner Mongolia University for Nationalities, Tongliao, 028000, China. FAU - Jin, Hua AU - Jin H AD - Affiliated Hospital of Inner Mongolia University of Nationalities, Tongliao, 028000, China. FAU - Liu, Guoli AU - Liu G AD - Affiliated Hospital of Inner Mongolia University of Nationalities, Tongliao, 028000, China. FAU - Feng, Yakai AU - Feng Y AD - School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Tianjin, 300350, China; Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Tianjin, 300350, China; Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, China. Electronic address: yakaifeng@tju.edu.cn. LA - eng PT - Journal Article DEP - 20200331 PL - Netherlands TA - Colloids Surf B Biointerfaces JT - Colloids and surfaces. B, Biointerfaces JID - 9315133 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cytokines) RN - 0 (NF-kappa B) RN - 369U7A6HXD (benzoylaconine) RN - X8YN71D5WC (Aconitine) SB - IM MH - Aconitine/administration & dosage/*analogs & derivatives MH - Animals MH - Anti-Inflammatory Agents/administration & dosage MH - Cytokines/metabolism MH - *Drug Delivery Systems MH - Edema/chemically induced/*drug therapy MH - Female MH - Inflammation/*drug therapy/immunology/pathology MH - Macrophages/*drug effects/immunology MH - NF-kappa B/genetics/*metabolism MH - Nanoparticles/*administration & dosage/chemistry MH - Rats OTO - NOTNLM OT - Benzoylaconitine OT - Inflammation OT - Nanoparticles OT - Rheumatoid arthritis COIS- Declaration of Competing Interest No conflict of interest exits in the submission of this manuscript, and the manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that this work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed. EDAT- 2020/04/07 06:00 MHDA- 2021/01/12 06:00 CRDT- 2020/04/07 06:00 PHST- 2019/11/26 00:00 [received] PHST- 2020/03/11 00:00 [revised] PHST- 2020/03/14 00:00 [accepted] PHST- 2020/04/07 06:00 [pubmed] PHST- 2021/01/12 06:00 [medline] PHST- 2020/04/07 06:00 [entrez] AID - S0927-7765(20)30210-1 [pii] AID - 10.1016/j.colsurfb.2020.110980 [doi] PST - ppublish SO - Colloids Surf B Biointerfaces. 2020 Jul;191:110980. doi: 10.1016/j.colsurfb.2020.110980. Epub 2020 Mar 31.