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Inhibition of human brain malignant glioblastoma cells using carmustine-loaded catanionic solid lipid nanoparticles
Yung-Chih Kuo1, Cheng-Te Liang
1Department of Chemical Engineering, National Chung Cheng University, Chia-Yi 62102, Taiwan, ROC. chmyck@ccu.edu.tw
Abstract:
Innovated catanionic solid lipid nanoparticles (CASLNs) carrying carmustine (BCNU) (BCNU-CASLNs) were grafted with anti-epithelial growth factor receptor (EGFR) (anti-EGFR/BCNU-CASLNs) and applied to inhibiting the propagation of human brain malignant glioblastomas cells. U87MG cells were treated with anti-EGFR/BCNU-CASLNs and stained for the expression of EGFR. The minimal average diameter of BCNU-CASLNs and maximal entrapment efficiency of BCNU emerged when the concentration of catanionic surfactants was 1 mm. An increase in the weight percentage of cacao butter (CB) reduced the zeta potential, enhanced the viability of human brain microvasscular endothelial cells (HBMECs), and decreased the expression of tumor necrosis factor-α by HBMECs. The dissolution rate of BCNU and inhibition against the multiplication of U87MG cells using anti-EGFR/BCNU-CASLNs followed the order: 100% CB > 0% CB > 50% CB. Anti-EGFR/BCNU-CASLNs demonstrated the properties including an effective delivery to U87MG cells and antiproliferative efficacy against the growth of malignant brain tumors.
Insights
Novel catanionic solid lipid nanoparticles (CASLNs) carrying carmustine (BCNU) were developed and targeted against glioblastoma cells using anti-epithelial growth factor receptor (EGFR) antibodies. These targeted nanoparticles effectively delivered BCNU to U87MG cells, inhibiting tumor growth.
Area of Science:
- Nanotechnology
- Drug Delivery Systems
- Oncology
Background:
- Glioblastoma is an aggressive brain tumor with limited treatment options.
- Targeted drug delivery systems are crucial for improving therapeutic efficacy and reducing side effects.
- Carmustine (BCNU) is a chemotherapeutic agent used against brain tumors.
Purpose of the Study:
- To develop and characterize novel catanionic solid lipid nanoparticles (CASLNs) loaded with carmustine (BCNU).
- To functionalize BCNU-loaded CASLNs with anti-epithelial growth factor receptor (EGFR) antibodies for targeted glioblastoma therapy.
- To evaluate the in vitro efficacy of anti-EGFR/BCNU-CASLNs against human glioblastoma U87MG cells.
Main Methods:
- Synthesis and characterization of BCNU-loaded CASLNs.
- Grafting of anti-EGFR antibodies onto BCNU-CASLNs.
- In vitro evaluation of nanoparticle size, zeta potential, and BCNU entrapment efficiency.
- Assessment of BCNU release kinetics and antiproliferative activity against U87MG cells.
- Evaluation of the effect of cacao butter percentage on nanoparticle properties and cell viability.
Main Results:
- Optimal BCNU-CASLNs formulation achieved minimal average diameter and maximal entrapment efficiency at 1 mM catanionic surfactant concentration.
- Increased cacao butter (CB) content reduced zeta potential and improved human brain microvascular endothelial cell (HBMEC) viability while decreasing TNF-α expression.
- The dissolution rate of BCNU and inhibition of U87MG cell proliferation followed the order: 100% CB > 0% CB > 50% CB.
- Anti-EGFR/BCNU-CASLNs demonstrated effective delivery to U87MG cells and significant antiproliferative efficacy.
Conclusions:
- Targeted anti-EGFR/BCNU-CASLNs represent a promising strategy for treating malignant glioblastomas.
- The formulation and composition, particularly the percentage of cacao butter, significantly influence nanoparticle performance and biological effects.
- These novel nanoparticles offer effective delivery and antiproliferative activity against brain tumor cells.
