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首页> 美国卫生研究院文献>PLoS Clinical Trials >Nanoparticle size and production efficiency are affected by the presence of fatty acids during albumin nanoparticle fabrication
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Nanoparticle size and production efficiency are affected by the presence of fatty acids during albumin nanoparticle fabrication

机译：白蛋白纳米粒子制造过程中脂肪酸的存在会影响纳米粒子的大小和生产效率

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We have previously identified extensive glycation, bound fatty acids and increased quantities of protein aggregates in commercially available recombinant HSA (rHSA) expressed in Oryza sativa (Asian rice) (OsrHSA) when compared to rHSA from other expression systems. We propose these differences may alter some attributes of nanoparticles fabricated with OsrHSA, as studies have associated greater quantities of aggregates with increased nanoparticle diameters. To determine if this is the case, nanoparticles were fabricated with OsrHSA from various suppliers using ethanol desolvation and subsequent glutaraldehyde cross-linking. All nanoparticles fabricated with OsrHSA showed larger diameters of approximately 20 to 90nm than particles fabricated with either defatted bovine serum albumin (DF-BSA) (100.9 ± 2.8nm) or human plasma albumin (pHSA) (112.0 ± 4.0nm). It was hypothesized that the larger nanoparticle diameters were due to the presence of bound fatty acids and this was confirmed through defatting OsrHSA prior to particle fabrication which yielded particles with diameters similar to those fabricated with pHSA. For additional conformation, DF-BSA was incubated with dodecanoic acid prior to desolvation yielding particles with significantly larger diameters. Further studies showed the increased nanoparticle diameters were due to the bound fatty acids modulating electrostatic interactions between albumin nanoparticles during the desolvation and not changes in protein structure, stability or generation of additional albumin oligomers. Finally the presence of dodecanoic acid was shown to improve doxorubicin loading efficiency onto preformed albumin nanoparticles.
机译：与其他表达系统的rHSA相比，我们先前已经确定了在水稻（亚洲稻）（OsrHSA）中表达的市售重组HSA（rHSA）中广泛的糖基化，结合的脂肪酸和数量增加的蛋白质聚集体。我们认为这些差异可能会改变用OsrHSA制备的纳米颗粒的某些属性，因为研究已将大量聚集体与增加的纳米颗粒直径相关联。为了确定是否存在这种情况，使用乙醇去溶剂化和随后的戊二醛交联，利用各种供应商的OsrHSA制备了纳米颗粒。用OsrHSA制备的所有纳米颗粒均比用脱脂牛血清白蛋白（DF-BSA）（100.9±2.8nm）或人血浆白蛋白（pHSA）（112.0±4.0nm）制备的颗粒具有更大的直径，约为20至90nm。假设较大的纳米颗粒直径是由于存在结合的脂肪酸，这可以通过在制备颗粒之前对OsrHSA脱脂来证实，该颗粒产生的粒径与用pHSA制备的直径相似。为了获得额外的构象，在去溶剂化之前，将DF-BSA与十二烷酸孵育，以产生直径明显更大的颗粒。进一步的研究表明，纳米颗粒直径的增加是由于结合的脂肪酸在去溶剂化过程中调节了白蛋白纳米颗粒之间的静电相互作用，而不是蛋白质结构，稳定性或其他白蛋白寡聚物的产生变化。最后，表明十二烷酸的存在可以提高阿霉素在预先形成的白蛋白纳米颗粒上的负载效率。

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