Preparation and cytotoxicity of 2-methoxyestradiol-loaded solid lipid nanoparticles.
The objective of this study was to prepare 2-methoxyestradiol (2-ME)-loaded solid lipid nanoparticles (SLN) by hot homogenization-ultrasonication and evaluate their cytotoxicity on three cell lines, breast cancer [Michigan Cancer Foundation-7 (MCF-7)], prostatic carcinoma (PC-3), and glioma (SK-N-SH), by the sulforhodamineB method. The particle sizes and zeta potentials of the prepared SLN were around 120 nm and -40 mV, respectively. Differential scanning calorimetry (DSC) measurements revealed that the monostearin and 2-ME existed in solid and amorphous states in the SLN prepared, respectively. The high drug entrapment efficiency (>85%) indicated that most 2-ME was incorporated in the SLN. An in-vitro drug release study showed that 2-ME was released from the SLN in a slow but time-dependent manner. The cytotoxicity of 2-ME in SLN on each cell line was significantly enhanced compared with the solution. 2-ME SLN composed of Tween80 was approximately 17-fold more effective on PC-3 cells and 6.7-fold more effective on SK-N-SH cells than in the solution, whereas a lower sensitivity was achieved on MCF-7 cells. In each cell line, the cellular uptake percentages of 2-ME in SLN were much higher than the solution, respectively. In addition, surfactants may exert different effects on the cytotoxicity of 2-ME SLN depending on the cell line. The above assay demonstrated that SLN could significantly enhance the cytotoxicity of 2-ME compared with the free drug because of the increased cellular internalization and concentration of 2-ME. The results suggested that SLN could be an excellent carrier candidate to entrap 2-ME for improving the effectiveness of tumor chemotherapy.
School of Pharmacy, Zhengzhou University, Zhengzhou, China.
Xinhong
X
Guo
Yabing
Y
Xing
Qian
Q
Mei
Hongling
H
Zhang
Zhenzhong
Z
Zhang
Fude
F
Cui
D000077584:2-Methoxyestradiol; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004958:Estradiol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D012995:Solubility; D013010:Sonication; D013499:Surface Properties
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D004958:Estradiol; D000077584:2-Methoxyestradiol