Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX, USA.
Anticancer Res. 2013 Jun;33(6):2425-34.
Extreme hydrophobicity and poor stability of SN-38, a highly potent topoisomerase I inhibitor, has prevented its clinical use. Its encapsulation into nanoparticles may be a way to overcome these problems. Here we report the use of SN-38-loaded hyaluronic acid (HA)-decorated poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) for targeted ovarian cancer therapy.
PLGA-PEG nanoparticles loaded with SN-38 were prepared by single- emulsion (O/W) solvent evaporation method. HA was decorated onto the nanoparticles by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) coupling and the extent of HA conjugation was quantified by hexadecyltrimmethylammonium bromide (CTAB) assay. Cancer cell specificity of the NPs was determined by flow cytometry and cytotoxicity of the NPs was tested by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium (MTT) bromide assay.
Mean size, zeta potential and encapsulation efficiency of PLGA-PEG-HA NPs were 265.6 ± 3.8 nm, -30.4 ± 0.1 mV and 75.8 ± 4.1%, respectively. Cellular uptake of PLGA-PEG-HA NPs was 8- and 16-fold higher in CD44-positive cell lines, SKOV-3 and OVCAR-8, as compared to CD44-negative cells (CHO). Cytotoxicity of the targeted NPs was significantly higher as compared to non-targeted NPs for the above cell lines. These results suggest that PLGA-PEG-HA NPs could be an efficient delivery system for SN-38 for targeted therapy of ovarian cancer.
由于高度有效的拓扑异构酶 I 抑制剂 SN-38 具有极强的疏水性和较差的稳定性，因此其无法在临床上使用。将其包封入纳米颗粒中可能是克服这些问题的一种方法。在这里，我们报告了使用载有 SN-38 的透明质酸（HA）修饰的聚乳酸-共-羟基乙酸-聚乙二醇（PLGA-PEG）纳米颗粒（NPs）进行靶向卵巢癌治疗。
通过单乳液（O/W）溶剂蒸发法制备载有 SN-38 的 PLGA-PEG 纳米颗粒。通过 1-乙基-3-（3-二甲基氨基丙基）碳化二亚胺（EDC）偶联将 HA 修饰到纳米颗粒上，并通过十六烷基三甲基溴化铵（CTAB）测定法定量 HA 接枝程度。通过流式细胞术测定 NPs 的癌细胞特异性，并通过 3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四唑溴盐（MTT）溴化物测定法测定 NPs 的细胞毒性。
PLGA-PEG-HA NPs 的平均粒径、Zeta 电位和包封效率分别为 265.6±3.8nm、-30.4±0.1mV 和 75.8±4.1%。PLGA-PEG-HA NPs 在 CD44 阳性细胞系 SKOV-3 和 OVCAR-8 中的细胞摄取量分别比 CD44 阴性细胞（CHO）高 8 倍和 16 倍。对于上述细胞系，靶向 NPs 的细胞毒性明显高于非靶向 NPs。这些结果表明，PLGA-PEG-HA NPs 可能是 SN-38 的有效递送系统，可用于卵巢癌的靶向治疗。
