Construction of a pH-responsive, ultralow-dose triptolide nanomedicine for safe rheumatoid arthritis therapy

Liu, Yang; Jin, Jianqiu; Xu, Hao; Wang, Chao; Yang, Yanping; Zhao, Yongjian; Han, Haihui; Hou, Tong; Yang, Guoliang; Zhang, Li; Wang, Yongjun; Zhang, Weian; Liang, Qianqian

doi:10.1016/j.actbio.2020.11.027

Cited by 57 publications

(28 citation statements)

References 40 publications

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“…The use of amphiphilic pH-sensitive galactosyl dextran-retinal (GDR) nanoparticles to encapsulate triptolide may enhance the anti-inflammatory effect of CIA mouse models 14 . The latest results confirmed that by encapsulating triptolide in the star-shaped amphiphilic block copolymer POSS-PCL-b-PDMAEMA, the constructed pH-sensitive triptolide nanomedicine can achieve significant anti-inflammatory effects at ultra-low doses to treat RA 15 . The use of nanomaterials to carry triptolide has many advantages, such as targeted drug delivery and reduced triptolide dose.…”

Section: Biological Functionssupporting

confidence: 58%

Triptolide: pharmacological spectrum, biosynthesis, chemical synthesis and derivatives

Gao¹,

Zhang²,

Liu³

et al. 2021

Theranostics

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Triptolide, an abietane-type diterpenoid isolated from Tripterygium wilfordii Hook. F., has significant pharmacological activity. Research results show that triptolide has obvious inhibitory effects on many solid tumors. Therefore, triptolide has become one of the lead compounds candidates for being the next "blockbuster" drug, and multiple triptolide derivatives have entered clinical research. An increasing number of researchers have developed triptolide synthesis methods to meet the clinical need. To provide new ideas for researchers in different disciplines and connect different disciplines with researchers aiming to solve scientific problems more efficiently, this article reviews the research progress made with analyzes of triptolide pharmacological activity, biosynthetic pathways, and chemical synthesis pathways and reported in toxicological and clinical studies of derivatives over the past 20 years, which have laid the foundation for subsequent researchers to study triptolide in many ways.

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Section: Biological Functionssupporting

confidence: 58%

Triptolide: pharmacological spectrum, biosynthesis, chemical synthesis and derivatives

Gao¹,

Zhang²,

Liu³

et al. 2021

Theranostics

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show abstract

“…Triptolide (TP), a diterpene triepoxide isolated from Tripterygium wilfordii Hook F, has been widely used to treat inflammatory and autoimmune diseases, such as systemic lupus erythematosus and RA, but its severe systemic toxicity, especially hepatotoxicity, nephrotoxicity, and cardiotoxicity, along with poor solubility, results in a narrow therapeutic window and poor bioavailability that limit its clinical application (Shen et al., 2019 ; Song et al., 2020 ; Liaw et al., 2021 ; Liu et al., 2021 ). TP has been demonstrated to exhibit anti-inflammatory and immunosuppressive activities, and TP derivatives have been demonstrated to inhibit the polarization of macrophages into the proinflammatory M1 phenotype (Shen et al., 2019 ; Fu et al., 2020 ; Liaw et al., 2021 ; Liu et al., 2021 ). Folic acid (FA)-modified liposomes (FA-Lips) have been demonstrated to have enhanced targeting efficiency by binding to FR with high affinity (Nogueira et al., 2015 ; Xue et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Targeted therapy of rheumatoid arthritis via macrophage repolarization

Huang

Wang

et al. 2021

Drug Delivery

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“…Previously studies have shown the therapeutic potential of TP in animal models of RA [30] . 14 days after building model, the mice were divided into 5 groups (n=6 in each group) at random and the dose of TP is 1mg/kg per body weight, respectively.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Acupoint Nanocomposite Hydrogel for Simulation of Acupuncture and Targeted Delivery of Triptolide Against Rheumatoid Arthritis

Ren

Liu

Wang

et al. 2021

Preprint

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BackgroundAttenuating the inﬂammatory response and relieving pain are two therapeutical goals for rheumatoid arthritis (RA). Anti-inflammatory and analgesic drugs are often associated with many adverse effects due to nonspecific distribution. New drug delivery systems with effective targeting ability and other complementary strategies are on urgent need to be explored. To achieve this goal, an acupoint drug delivery system that can simulate acupuncture in relieving pain and targeted deliver anti-inflammatory drugs is constructed, which can co-deliver 2-chloro-N (6)-cyclopentyl adenosine (CCPA) and triptolide (TP). ResultsWe have successfully demonstrated that the nanocomposite hydrogel composed of TP-Human serum album nanoparticles (HSA NPs) and CCPA could effectively treat the RA. We found that this combination therapy can enhance analgesic effects while the mechanical pain threshold was 5.2 times compared with model group, and the thermal pain threshold was 1.4 times. Acupoint nanocomposite hydrogel could not only improve the accumulation of the designed nanomedicine in arthritic paws (13.5% higher than those in non-acupoint at 48h), but also cooperate with nanomedicine to exert synergetic improvement of inflammation and reduction of systemic toxicity. Furthermore, it can regulate inflammatory factors and restore the balance of Th17/Treg cell which provide a novel effective treatment strategy for RA.ConclusionThis novel therapeutic approach-acupoint nanocomposite hydrogel, builds a bridge between acupuncture and drugs which sheds light on the combination of traditional and modern medicine.

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Construction of a pH-responsive, ultralow-dose triptolide nanomedicine for safe rheumatoid arthritis therapy

Cited by 57 publications

References 40 publications

Triptolide: pharmacological spectrum, biosynthesis, chemical synthesis and derivatives

Triptolide: pharmacological spectrum, biosynthesis, chemical synthesis and derivatives

Targeted therapy of rheumatoid arthritis via macrophage repolarization

Acupoint Nanocomposite Hydrogel for Simulation of Acupuncture and Targeted Delivery of Triptolide Against Rheumatoid Arthritis

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