Overcoming the Druggability Hurdles of Celastrol: A Critical Review of Advanced Drug Delivery Strategies

Celastrol, one of the top five traditional natural products with high potential for modern drug development, exerts potent broad-spectrum biological activities, yet its poor aqueous solubility, low bioavailability, potential toxicity, and limited selectivity severely compromise its drug-likeness. Advanced drug delivery strategies, mainly including multifunctional polymer/lipid/protein-based organic nanoparticles, metal/silica-based inorganic nanoparticles, vesicles represented by liposomes, and nanoemulsions, are expected to overcome these druggability hurdles of celastrol via oral, transdermal or intravenous administration. This review summarizes recent progress in a series of celastrol formulations, including novel dosage forms and delivery routes accompanied with consequential pharmacological effects and mechanisms of action, which have the potential to bring about better druggability conducive to future medical treatment.