Recent progress in nanotechnology-based drug carriers for celastrol delivery

Guo, Litao; Zhang, Yongping; Al‐Jamal, Khuloud T.

doi:10.1039/d1bm00639h

Cited by 22 publications

(10 citation statements)

References 124 publications

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“…Similar to triptolide, celastrol can also be loaded by nanomaterials, which in turn reduces toxicity, increases bioavailability and enhances therapeutic efficacy. Studies have shown that celastrol can be loaded by various types of nanomaterials, such as liposomes, lipid nanoparticles, and exosomes, and the nanomaterials loaded with celastrol are used to treat various diseases ( Guo et al, 2021 ). However, studies on nanotechnology-based carrier system of triptolide and celastrol are mainly about cancer therapy, and there are fewer studies related to neurological diseases ( Liaw et al, 2021 ; Geng et al, 2022 ).…”

Section: Toxicity and Derivativesmentioning

confidence: 99%

The therapeutic potential of triptolide and celastrol in neurological diseases

2022

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Neurological diseases are complex diseases affecting the brain and spinal cord, with numerous etiologies and pathogenesis not yet fully elucidated. Tripterygium wilfordii Hook. F. (TWHF) is a traditional Chinese medicine with a long history of medicinal use in China and is widely used to treat autoimmune and inflammatory diseases such as systemic lupus erythematosus and rheumatoid arthritis. With the rapid development of modern technology, the two main bioactive components of TWHF, triptolide and celastrol, have been found to have anti-inflammatory, immunosuppressive and anti-tumor effects and can be used in the treatment of a variety of diseases, including neurological diseases. In this paper, we summarize the preclinical studies of triptolide and celastrol in neurological diseases such as neurodegenerative diseases, brain and spinal cord injury, and epilepsy. In addition, we review the mechanisms of action of triptolide and celastrol in neurological diseases, their toxicity, related derivatives, and nanotechnology-based carrier system.

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Section: Toxicity and Derivativesmentioning

confidence: 99%

The therapeutic potential of triptolide and celastrol in neurological diseases

2022

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“…Overall, even though celastrol is so biologically active, its non-selectivity with respect to cytotoxicity towards normal cell lines is an issue, as has been noted on many occasions previously. Clearly, evaluation of selective formulation methods (Huang, T, et al, 2020;Shi et al, 2020;Guo et al, 2021;Wagh et al, 2021) or of relatively non-toxic derivatives (Klaić et al, 2012;Bassanini et al, 2021;Coghi et al, 2021) must continue in order to develop celastrol as a potent and successful drug.…”

Section: Discussionmentioning

confidence: 99%

“…However, although celastrol is a biologically potent compound, it displays untoward toxicity associated with numerous off-target effects. Thus, considerable effort has been directed towards development of controlled-release formulations of celastrol (Huang., et al, 2020;Shi et al, 2020;Guo et al, 2021;Wagh et al, 2021) or preparation of less toxic derivatives largely Frontiers in Pharmacology frontiersin.org associated with conversion of the carboxylic acid to amide derivatives (Klaić et al, 2012;Bassanini et al, 2021;Coghi et al, 2021). Antimalarial activities of celastrol and its naturally-occurring methyl ester pristimerin (Figure 4) have been reported (Figueiredo et al, 1998;Li et al, 2019); for celastrol, IC 50 activities against the chloroquine sensitive Pf NF54 strain and multidrug resistant Pf K1 strain are 564 and 401 nM respectively, with similar values for pristimerin (IC 50 NF54 583 nM, K1 409 nM).…”

Section: Introductionmentioning

confidence: 99%

Antimalarial and antitumour activities of the steroidal quinone-methide celastrol and its combinations with artemiside, artemisone and methylene blue

Han

et al. 2022

Front. Pharmacol.

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Artemisinin, isolated from the traditional Chinese medicinal plant qīng hāo 青蒿 (Artemisia annua) and its derivatives are used for treatment of malaria. With treatment failures now being recorded for the derivatives and companion drugs used in artemisinin combination therapies new drug combinations are urgently required. The amino-artemisinins artemiside and artemisone display optimal efficacies in vitro against asexual and sexual blood stages of the malaria parasite Plasmodium falciparum and are active against tumour cell lines. In continuing the evolution of combinations of the amino-artemisinins with new drugs, we examine the triterpenoid quinone methide celastrol isolated from the traditional Chinese medicinal plant léi gōng téng 雷公藤 (Tripterygium wilfordii). This compound is redox active, and has attracted considerable attention because of potent biological activities against manifold targets. We report that celastrol displays good IC50 activities ranging from 0.50–0.82 µM against drug-sensitive and resistant asexual blood stage Pf, and 1.16 and 0.28 µM respectively against immature and late stage Pf NF54 gametocytes. The combinations of celastrol with each of artemisone and methylene blue against asexual blood stage Pf are additive. Given that celastrol displays promising antitumour properties, we examined its activities alone and in combinations with amino-artemisinins against human liver HepG2 and other cell lines. IC50 values of the amino-artemisinins and celastrol against HepG2 cancer cells ranged from 0.55–0.94 µM. Whereas the amino-artemisinins displayed notable selectivities (SI > 171) with respect to normal human hepatocytes, in contrast, celastrol displayed no selectivity (SI < 1). The combinations of celastrol with artemiside or artemisone against HepG2 cells are synergistic. Given the promise of celastrol, judiciously designed formulations or structural modifications are recommended for mitigating its toxicity.

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“…23 Also, the translational study of CLT is greatly limited by its poor solubility and off-target toxicity. 24 Recently, drug delivery systems have been attempted to resolve the aforementioned limitations of CLT, including liposomes, 25 phytosomes, 26 bilosomes, 27 polymeric nanoparticles, 28 and micelles, 19 via either active or passive targeting strategies. CLT-loaded liposomes modified with galactose are synthesized to achieve targeted therapy of hepatocellular carcinoma by actively targeting asialoglycoprotein receptor-enriched cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Chondroitin Sulfate-Derived Micelles for Adipose Tissue-Targeted Delivery of Celastrol and Phenformin to Enhance Obesity Treatment

Niu,

Gao,

Ouyang

et al. 2024

ACS Appl. Bio Mater.

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Adipose tissue macrophages (ATMs) are crucial in maintaining a low-grade inflammatory microenvironment in adipose tissues (ATs). Modulating ATM polarization to attenuate inflammation represents a potential strategy for treating obesity with insulin resistance. This study develops a combination therapy of celastrol (CLT) and phenformin (PHE) using chondroitin sulfate-derived micelles. Specifically, CLT-loaded 4-aminophenylboronic acid pinacol ester-modified chondroitin sulfate micelle (CS-PBE/CLT) and chondroitin sulfate-phenformin conjugate micelles (CS-PHE) were synthesized, which were shown to actively target ATs through CD44-mediated pathways. Furthermore, the dual micellar systems significantly reduced inflammation and lipid accumulation via protein quantification and Oil Red O staining. In preliminary in vivo studies, we performed H&E staining, immunohistochemical staining, insulin tolerance test, and glucose tolerance test, and the results showed that the combination therapy using CS-PBE/CLT and CS-PHE micelles significantly reduced the average body weight, white adipose tissue mass, and liver mass of high-fat diet-fed mice while improving their systemic glucose homeostasis. Overall, this combination therapy presents a promising alternative to current treatment options for diet-induced obesity.

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Recent progress in nanotechnology-based drug carriers for celastrol delivery

Abstract: Various types of celastrol nanoformulations have been developed to treat a number of disorders, including cancer, inflammatory, auto-immune, obesity.

Cited by 22 publications

References 124 publications

The therapeutic potential of triptolide and celastrol in neurological diseases

The therapeutic potential of triptolide and celastrol in neurological diseases

Antimalarial and antitumour activities of the steroidal quinone-methide celastrol and its combinations with artemiside, artemisone and methylene blue

Chondroitin Sulfate-Derived Micelles for Adipose Tissue-Targeted Delivery of Celastrol and Phenformin to Enhance Obesity Treatment

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