Nanoparticles containing anti-inflammatory agents as chemotherapy adjuvants:: Optimization and in vitro characterization
Nanoparticles containing anti-inflammatory agents as chemotherapy adjuvants:: Optimization and in vitro characterization
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DOI：
10.1208/s12248-008-9013-z
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发表时间：
2008-03-01
期刊：
影响因子：
4.5
通讯作者：
Leggas, Markos
中科院分区：
文献类型：
--
作者：
Lu, Xiuling;Howard, Melissa D.;Leggas, Markos
地塞米松（DEX）的预施用先前已显示增强化学治疗剂的抗肿瘤功效。通过纳米颗粒载体将抗炎剂特异性地递送至肿瘤预期将促进化疗剂的有效性，同时避免全身毒性。优化了纳米模板工程法制备抗炎药物固体脂质纳米粒的工艺。由于DEX在本体水相中的增溶作用，合成了其更亲脂的棕榈酸酯，并将其掺入纳米颗粒中，该纳米颗粒包括聚乙二醇化剂PEG 6000单硬脂酸酯，作为制剂的一部分。通过测量放射性碘标记的IgG的吸附（185 μ g对6.7 μ g IgG/mg NP），证明这些纳米颗粒的隐形性质比胶乳颗粒增强。此外，随着制剂中聚乙二醇化剂的量从0增加到4 mg/mL，鼠巨噬细胞对C-14标记的纳米颗粒的摄取显示从36.6%纳米颗粒/mg细胞蛋白降低到14.7%。对于这些含DEX棕榈酸酯的纳米颗粒观察到的高负载值和低爆发效应，除了它们的隐形性质之外，预期允许将足够量的DEX递送至肿瘤以增强化疗剂的摄取。
The pre-administration of dexamethasone (DEX) has previously been shown to enhance the anti-tumor efficacy of chemotherapeutic agents. The delivery of anti-inflammatory agents specifically to tumors via nanoparticle carriers is expected to promote the effectiveness of chemotherapeutic agents while avoiding systemic toxicities. The process for preparing solid lipid nanoparticles containing anti-inflammatory agents using the nanotemplate engineering method was optimized. Due to the solubilization of DEX in the bulk aqueous phase, its more lipophilic palmitate ester was synthesized and incorporated in nanoparticles that included a pegylating agent, PEG6000 mono-stearate, as part of the formulation. The stealth properties of these nanoparticles were demonstrated to be enhanced compared to latex particles by measuring the adsorption of radioiodinated IgG (185 mu g vs. 6.7 mu g IgG/mg NP). In addition, the uptake of C-14-labeled nanoparticles by murine macrophages was shown to decrease from 36.6% to 14.7% of the nanoparticles/mg cell protein as the amount of pegylating agent in the formulation increased from 0 to 4 mg/mL. The high loading values and low burst effect observed for these DEX palmitate-containing nanoparticles in addition to their stealth properties are expected to allow for the delivery of sufficient amounts of DEX to tumors to enhance the uptake of chemotherapeutic agents.