{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:44:45Z","timestamp":1785422685212,"version":"3.56.0"},"reference-count":65,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005270","name":"Fujian Provincial Science and Technology Department","doi-asserted-by":"crossref","award":["2023R1011002"],"award-info":[{"award-number":["2023R1011002"]}],"id":[{"id":"10.13039\/501100005270","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2023R1011002"],"award-info":[{"award-number":["2023R1011002"]}],"id":[{"id":"https:\/\/ror.org\/00rgzpv08","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Fujian Provincial Medical Innovation Projects","award":["2017-CXB-4"],"award-info":[{"award-number":["2017-CXB-4"]}]},{"DOI":"10.13039\/501100014125","name":"Fujian Provincial Health Commission","doi-asserted-by":"crossref","award":["2024CXA045"],"award-info":[{"award-number":["2024CXA045"]}],"id":[{"id":"10.13039\/501100014125","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2024CXA045"],"award-info":[{"award-number":["2024CXA045"]}],"id":[{"id":"https:\/\/ror.org\/0136mc929","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Triptolide (TP), a potent natural diterpenoid, exhibits anti-glioma activity, but faces significant clinical translation challenges, including poor water solubility, systemic toxicity such as hepatotoxicity, and inadequate tumor targeting. This study aimed to develop a novel epidermal growth factor receptor (EGFR)-targeted liposomal formula-tion, designated as TP-CTX-Lip (where CTX denotes cetuximab), to enhance the deliv-ery efficiency and therapeutic window of TP. Methods: The formulation was optimized using a uniform design approach (four factors, six levels) and prepared via thin-film hydra-tion\u2013ultrasonication. The encapsulation of TP was supported by Fourier transform in-frared spectroscopy (FTIR) and thermal analysis (DSC\/TGA), which revealed molecu-lar interactions (e.g., hydrogen bonding) with lipid components and a marked en-hancement in thermal stability, consistent with successful incorporation into the lipo-somal bilayer. The physicochemical properties, including the size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and drug loading, were characterized. In vitro release kinetics were evaluated in phosphate buffer (pH 7.4), and cytotoxicity was assessed in high-EGFR (U87-MG) and low-EGFR (SW1088) glioma cells. In vivo efficacy and developmental toxicity were investigated using zebrafish models. The op-timized TP-CTX-Lip demonstrated favorable characteristics: size = 131.3 \u00b1 4.5 nm, PDI = 0.24 \u00b1 0.006, zeta potential = \u221223.37 \u00b1 0.27 mV, encapsulation efficiency = 85.83% \u00b1 1.81%, and drug loading = 13%. In vitro release followed first-order kinetics dominated by Higuchi diffusion (79.0% \u00b1 4% at 24 h). After 48 h of treatment, TP-CTX-Lip exhib-ited significantly enhanced cytotoxicity in U87-MG cells (IC50 = 10.4 \u00b1 0.2 nM), com-pared with IC50 values of 42.8 nM in SW1088 cells and 45.3 nM for non-targeted lipo-somes. In the 3T3-L1 non-cancerous cell line, the 48 h IC50 value of TP-CTX-Lip (8.433 \u00b1 0.954\u00b5M) was higher than that of the TP solution (2.173 \u00b1 0.181\u00b5M) but lower than that of TP-Lip (25.78 \u00b1 2.691\u00b5M). Specifically, in 3T3-L1 cells, the 48 h IC50 of TP-CTX-Lip (8.43 \u00b5M) was approximately 4-fold higher than that of free TP (2.17 \u00b5M), confirming its substantially reduced cytotoxicity against non-cancerous cells. Results: In comparison to TP-Lip and free FITC solution, the uptake rate of TP-CTX-Lip in U87-MG cells exhibited a significantly higher level. Specifically, the uptake rate for the TP-CTX-Lip group (57.46 \u00b1 5.44%) was statistically significantly higher than that of TP-Lip (13.7 \u00b1 2.33%) and the free FITC solution group (20.97 \u00b1 1.60%) (p &lt; 0.01). In zebrafish, TP-CTX-Lip reduced developmental toxicity, with LC50 increased 1.26 times to 5.733 \u03bcg\/mL, and suppressed orthotopic U87-MG xenograft growth (p &lt; 0.001), in-dicating an improved therapeutic window as reflected by the LC50\/IC50 ratio. Conclusions: the EGFR-targeted TP-CTX-Lip significantly enhances the tumor selectivity and safety of TP, providing a promising strategy for targeted glioma therapy.<\/jats:p>","DOI":"10.3390\/ph19050731","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T12:15:07Z","timestamp":1778156107000},"page":"731","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Construction of EGFR-Targeted Triptolide Liposomes Using Uniform Design Optimization and Therapeutic Evaluation in Gliomas"],"prefix":"10.3390","volume":"19","author":[{"given":"Huiqing","family":"Que","sequence":"first","affiliation":[{"name":"Fujian Key Laboratory of Medical Analysis, Fujian Academy of Medical Sciences, Fuzhou 350001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Medical Analysis, Fujian Academy of Medical Sciences, Fuzhou 350001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziting","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Ma","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Medical Analysis, Fujian Academy of Medical Sciences, Fuzhou 350001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4467-7628","authenticated-orcid":false,"given":"Junyong","family":"Han","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Medical Analysis, Fujian Academy of Medical Sciences, Fuzhou 350001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenmin","family":"Liu","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Medical Analysis, Fujian Academy of Medical Sciences, Fuzhou 350001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Xu","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Medical Analysis, Fujian Academy of Medical Sciences, Fuzhou 350001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Qian","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Medical Analysis, Fujian Academy of Medical Sciences, Fuzhou 350001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjin","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Bee Science and Biomedicine, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxu","family":"Liu","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Medical Analysis, Fujian Academy of Medical Sciences, Fuzhou 350001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.neulet.2012.08.003","article-title":"Gene Therapy for Brain Tumors: Basic Developments and Clinical Implementation","volume":"527","author":"Assi","year":"2012","journal-title":"Neurosci. 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