Habibi Nahal, Mauser Ava, Raymond Jeffery E, Lahann Joerg
Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
Beilstein J Nanotechnol. 2022 Feb 28;13:274-283. doi: 10.3762/bjnano.13.22. eCollection 2022.
Nanoparticles are frequently pursued as drug delivery carriers due to their potential to alter the pharmacological profiles of drugs, but their broader utility in nanomedicine hinges upon exquisite control of critical nanoparticle properties, such as shape, size, or monodispersity. Electrohydrodynamic (EHD) jetting is a probate method to formulate synthetic protein nanoparticles (SPNPs), but a systematic understanding of the influence of crucial processing parameters, such as protein composition, on nanoparticle morphologies is still missing. Here, we address this knowledge gap by evaluating formulation trends in SPNPs prepared by EHD jetting based on a series of carrier proteins and protein blends (hemoglobin, transferrin, mucin, or insulin). In general, blended SPNPs presented uniform populations with minimum diameters between 43 and 65 nm. Size distributions of as-jetted SPNPs approached monodispersity as indicated by polydispersity indices (PDI) ranging from 0.11-0.19. Geometric factor analysis revealed high circularities (0.82-0.90), low anisotropy (<1.45) and excellent roundness (0.76-0.89) for all SPNPs prepared via EHD jetting. Tentatively, blended SPNPs displayed higher circularity and lower anisotropy, as compared to single-protein SPNPs. Secondary statistical analysis indicated that blended SPNPs generally present combined features of their constituents, with some properties driven by the dominant protein constituent. Our study suggests SPNPs made from blended proteins can serve as a promising drug delivery carrier owing to the ease of production, the composition versatility, and the control over their size, shape and dispersity.
纳米颗粒因其改变药物药理学特性的潜力而经常被用作药物递送载体，但其在纳米医学中的更广泛应用取决于对关键纳米颗粒特性（如形状、大小或单分散性）的精确控制。电液动力（EHD）喷射是一种制备合成蛋白质纳米颗粒（SPNP）的有效方法，但对关键加工参数（如蛋白质组成）对纳米颗粒形态的影响仍缺乏系统的了解。在这里，我们通过评估基于一系列载体蛋白和蛋白质混合物（血红蛋白、转铁蛋白、粘蛋白或胰岛素）通过EHD喷射制备的SPNP的配方趋势来填补这一知识空白。一般来说，混合的SPNP呈现出均匀的群体，最小直径在43至65纳米之间。喷射后的SPNP的尺寸分布接近单分散性，多分散指数（PDI）范围为0.11 - 0.19。几何因子分析显示，通过EHD喷射制备的所有SPNP都具有高圆度（0.82 - 0.90）、低各向异性（<1.45）和优异的圆度（0.76 - 0.89）。初步来看，与单蛋白SPNP相比，混合的SPNP显示出更高的圆度和更低的各向异性。二次统计分析表明，混合的SPNP通常呈现其成分的组合特征，一些特性由主要蛋白质成分驱动。我们的研究表明，由混合蛋白质制成的SPNP由于生产简便、成分多样以及对其大小、形状和分散性的控制，可作为一种有前途的药物递送载体。
