Nanotechnology-Based Celastrol Formulations and Their Therapeutic Applications

Abstract

Celastrol (also called tripterine) is a quinone methide triterpene isolated from the root extract of Tripterygium wilfordii (thunder god vine in traditional Chinese medicine). Over the past two decades, celastrol has gained wide attention as a potent anti-inflammatory, anti-autoimmune, anti-cancer, anti-oxidant, and neuroprotective agent. However, its clinical translation is very challenging due to its lower aqueous solubility, poor oral bioavailability, and high organ toxicity. To deal with these issues, various formulation strategies have been investigated to augment the overall celastrol efficacy in vivo by attempting to increase the bioavailability and/or reduce the toxicity. Among these, nanotechnology-based celastrol formulations are most widely explored by pharmaceutical scientists worldwide. Based on the survey of literature over the past 15 years, this mini-review is aimed at summarizing a multitude of celastrol nanoformulations that have been developed and tested for various therapeutic applications. In addition, the review highlights the unmet need in the clinical translation of celastrol nanoformulations and the path forward.

Modulation of Inflammation-Related Lipid Mediator Pathways by Celastrol During Human Macrophage Polarization

“…It is interesting that a variety of nanotechnology-based CS formulations have been developed that were able to reduce the toxicity and/or improved bioavailability. 64 Future investigations of nanotechnology-based CS formulations in our experimental systems of macrophage polarization and LM biosynthesis might reveal if cytotoxicity and SPM-impairing effects may be circumvented. Indeed, drug delivery by nanofluids improved the efficacy of isoniazid 65 or of bromocriptine, 66 and encapsulation of a cytotoxic indirubin derivative into polymer-based nanoparticles reduced its detrimental impact on monocyte viability.…”

Reverse anti-breast cancer drug resistance effects by a novel two-step assembled nano-celastrol medicine

“…[8][9][10] As previously reported, CST showed significant antitumor effects on sundry tumor models via different mechanisms, such as osteosarcoma, 11 colorectal cancer, 12 and pancreatic cancer. 13 Furthermore, CST also markedly reduced the level of drug resistance of various human cancer cell cultures. Altogether, natural products from TCM, such as CST, exhibited chemotherapeutic activities as well as drug resistance reversal ability.…”

Neuroprotective Effects of Celastrol in Neurodegenerative Diseases-Unscramble Its Major Mechanisms of Action and Targets

“…The studies on improving oral bioavailability, toxicity reduction and maximize efficacy of celastrol will further step into a new phase with the progress of nanotechnology, quantitative chemical proteomics, single cell sequencing and in-depth research of mechanisms. For example, nanotechnology-based numerous celastrol formulations have been widely investigated and showed great success to reduce systemic toxicity and enhance the bioavailability of celastrol [ 140 , 141 ].…”