用于人类单核细胞-巨噬细胞药物递送的纳诺艺术合成、表征、摄取、释放和毒理学。
NanoART synthesis, characterization, uptake, release and toxicology for human monocyte-macrophage drug delivery.
机构信息
Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
出版信息
Nanomedicine (Lond). 2009 Dec;4(8):903-17. doi: 10.2217/nnm.09.71.
BACKGROUND
Factors limiting the efficacy of conventional antiretroviral therapy for HIV-1 infection include treatment adherence, pharmacokinetics and penetration into viral sanctuaries. These affect the rate of viral mutation and drug resistance. In attempts to bypass such limitations, nanoparticles containing ritonavir, indinavir and efavirenz (described as nanoART) were manufactured to assess macrophage-based drug delivery.
METHODS
NanoART were made by high-pressure homogenization of crystalline drug with various surfactants. Size, charge and shape of the nanoparticles were assessed. Monocyte-derived macrophage nanoART uptake, drug release, migration and cytotoxicity were determined. Drug levels were measured by reverse-phase high-performance liquid chromatography.
RESULTS
Efficient monocyte-derived macrophage cytoplasmic vesicle uptake in less than 30 min based on size, charge and coating was observed. Antiretroviral drugs were released over 14 days and showed dose-dependent reduction in progeny virion production and HIV-1 p24 antigen. Cytotoxicities resulting from nanoART carriage were limited.
CONCLUSION
These results support the continued development of macrophage-mediated nanoART carriage for HIV-1 disease.
背景
限制 HIV-1 感染常规抗逆转录病毒治疗疗效的因素包括治疗依从性、药代动力学和进入病毒避难所。这些因素会影响病毒突变和耐药性的速度。为了绕过这些限制，人们制造了含有利托那韦、茚地那韦和依非韦伦（称为纳米 ART）的纳米颗粒，以评估基于巨噬细胞的药物输送。
方法
通过高压匀化法将结晶药物与各种表面活性剂混合制成纳米 ART。评估了纳米颗粒的大小、电荷和形状。测定单核细胞衍生的巨噬细胞纳米 ART 的摄取、药物释放、迁移和细胞毒性。通过反相高效液相色谱法测量药物水平。
结果
基于大小、电荷和涂层，观察到不到 30 分钟内高效的单核细胞衍生的巨噬细胞胞质小泡摄取。抗逆转录病毒药物在 14 天内释放，并显示出剂量依赖性减少后代病毒粒子的产生和 HIV-1 p24 抗原。纳米 ART 携带产生的细胞毒性有限。
结论
这些结果支持继续开发巨噬细胞介导的纳米 ART 携带用于 HIV-1 疾病。
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