{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:42:27Z","timestamp":1792456947068,"version":"4.5.0"},"reference-count":26,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Objective: The aim of this study was to optimize the formulation of a C60-modified self-microemulsifying drug delivery system loaded with triptolide (C60-SMEDDS\/TP) and evaluate the cytoprotective effect of the C60-SMEDDS\/TP on normal human cells. Results: The C60-SMEDDS\/TP exhibited rapid emulsification, an optimal particle size distribution of 50 \u00b1 0.19 nm (PDI 0.211 \u00b1 0.049), and a near-neutral zeta potential of \u22121.60 mV. The release kinetics of TP from the C60-SMEDDS\/TP exhibited a sustained release profile and followed pseudo-first-order release kinetics. Cellular proliferation and apoptosis analysis indicated that the C60-SMEDDS\/TP (with a mass ratio of TP: DSPE-PEG-C60 = 1:10) exhibited lower toxicity towards L02 and GES-1 cells. This was demonstrated by a higher IC50 (40.88 nM on L02 cells and 17.22 nM on GES-1 cells) compared to free TP (21.3 nM and 11.1 nM), and a lower apoptosis rate (20.8% on L02 cells and 26.3% on GES-1 cells, respectively) compared to free TP (50.5% and 47.0%) at a concentration of 50 nM. In comparison to the free TP group, L02 cells and GES-1 cells exposed to the C60-SMEDDS\/TP exhibited a significant decrease in intracellular ROS and an increase in mitochondrial membrane potential (\u0394\u03c8M). On the other hand, the C60-SMEDDS\/TP demonstrated a similar inhibitory effect on BEL-7402 cells (IC50 = 28.9 nM) and HepG2 cells (IC50 = 107.6 nM), comparable to that of the free TP (27.2 nM and 90.4 nM). The C60-SMEDDS\/TP group also exhibited a similar intracellular level of ROS and mitochondrial membrane potential compared to the SMEDDS\/TP and free TP groups. Method: Fullerenol-Grafted Distearoyl Phosphatidylethanolamine-Polyethylene Glycol (DSPE-PEG-C60) was synthesized and applied in the self-microemulsifying drug delivery system. The C60-SMEDDS\/TP was formulated using Cremophor EL, medium-chain triglycerides (MCT), PEG-400, and DSPE-PEG-C60, and loaded with triptolide (TP). The toxicity and bioactivity of the C60-SMEDDS\/TP were assessed using normal human liver cell lines (L02 cells), normal human gastric mucosal epithelial cell lines (GES-1 cells), and liver cancer cell lines (BEL-7402 cells and HepG2 cells). The production of reactive oxygen species (ROS) after the C60-SMEDDS\/TP treatment was assessed using 2\u2032,7\u2032-dichlorofluorescein diacetate (DCFDA) staining. The alterations in mitochondrial membrane potential (\u0394\u03c8M) were assessed by measuring JC-1 fluorescence. Conclusions: The cytoprotection provided by the C60-SMEDDS\/TP favored normal cells (L02 and GES-1) over tumor cells (BEL-7402 and HepG2 cells) in vitro. This suggests a promising approach for the safe and effective treatment of TP.<\/jats:p>","DOI":"10.3390\/molecules29174073","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T07:52:08Z","timestamp":1724831528000},"page":"4073","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Cytoprotective Effect of C60 Derivatives in the Self-Microemulsifying Drug Delivery System against Triptolide-Induced Cytotoxicity In Vitro"],"prefix":"10.3390","volume":"29","author":[{"given":"Beihua","family":"Xu","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjie","family":"Tang","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongpeng","family":"Ding","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruihao","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihong","family":"Ding","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3608-3496","authenticated-orcid":false,"given":"Senlin","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.biopha.2018.05.088","article-title":"Broad targeting of triptolide to resistance and sensitization for cancer therapy","volume":"104","author":"Hou","year":"2018","journal-title":"Biomed. 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