Synthesis of novel hydrophilic celastrol nanoformulation by entrapment within calcium phosphate nanoparticle and study of its antioxidant activity against neurotoxin-induced damage in human neuroblastoma cells

Celastrol, a pentacyclic triterpenoid found in Chinese herb Tripterygium wilfordii, is considered as one of the top-five natural medicinal compounds with high antioxidant property. However, celastrol has poor aqueous solubility and thereby low bioavailability, restricting its clinical application as drug. To overcome this problem, we nanonized celastrol by entrapping it within hydrophilic nanocarrier – calcium phosphate nanoparticle. The synthesized calcium phosphate celastrol nanoparticle (CPCN) had average size of 35 nm, spherical shape, significant stability with (−) 37 mV zeta potential, celastrol entrapment efficiency around 75 % and low celastrol release kinetics spanning over 7 days, as measured by different techniques like FESEM, AFM, DLS, and spectrophotometry. Studies on the antioxidant potency of CPCN by flow cytometry and fluorescence microscopy depicted that the toxicity developed in human neuroblastoma cells SH-SY5Y by treatment with the selective neurotoxin MPP+ iodide (N-Methyl-4-phenylpyridinium iodide) got reduced by pretreatment of the cells with CPCN. Determination of cellular ROS content, depolarization level of mitochondrial membrane potential, cell cycle analysis and nuclear damage in MPP+-exposed cells demonstrated that CPCN had about 65 % more antioxidant efficacy over that of bulk celastrol. Thus, the nanonization process transformed hydrophobic celastrol into hydrophilic CPCN, having high potentiality to be developed as an effective antioxidant drug. [Display omitted] •Synthesis of calcium phosphate celastrol nanoparticle (CPCN) has been reported here.•CPCN was made by entrapping celastrol within calcium phosphate nanoparticle (CPNP).•CPNP made water-insoluble celastrol to water-soluble CPCN.•CPCN had more in vitro antioxidant and iron chelation activity than bulk celastrol.•CPCN had antioxidant activity against MPP + -induced toxicity in SH-SY5Y cells.