Scalable production and complete biophysical characterization of poly(ethylene glycol) surface conjugated liposome encapsulated hemoglobin (PEG-LEH).
Scalable production and complete biophysical characterization of poly(ethylene glycol) surface conjugated liposome encapsulated hemoglobin (PEG-LEH).
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DOI：
10.1371/journal.pone.0269939
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
颗粒包封的血红蛋白（Hb）为基础的氧（O2）载体（HBOCs）具有明显的优势，因为它们的大分子直径和缺乏血管活性的输血时，他们的非细胞对应物。聚乙二醇表面结合脂质体包裹血红蛋白（PEG-LEH）纳米粒被认为是一类有前途的HBOC，用作红细胞（RBC）替代品。然而，它们的广泛使用受到阻止材料规模化的制造工艺的限制。在这项研究中，PEG-LEH纳米粒子是通过一个可扩展的和强大的过程中使用高压细胞破碎机，其生物物理特性进行了彻底的表征。Hb包封、高铁血红蛋白（metHb）水平、O2-PEG-LEH平衡、PEG-LEH气态（氧气、一氧化碳、一氧化氮）配体结合/释放动力学、脂比容和长期储存稳定性使我们能够检查其作为RBC替代品的潜在适用性和有效性。我们的研究结果表明，通过高压细胞破碎机制造的PEG-LEH纳米颗粒悬浮液具有与全血相当的Hb浓度（约12 g/dL），并具有其他理想的特性，这可能允许它们用作潜在的救生O2治疗剂。
Particle encapsulated hemoglobin (Hb)-based oxygen (O2) carriers (HBOCs) have clear advantages over their acellular counterparts because of their larger molecular diameter and lack of vasoactivity upon transfusion. Poly(ethylene glycol) surface conjugated liposome encapsulated Hb (PEG-LEH) nanoparticles are considered a promising class of HBOC for use as a red blood cell (RBC) substitute. However, their widespread usage is limited by manufacturing processes which prevent material scale up. In this study, PEG-LEH nanoparticles were produced via a scalable and robust process using a high-pressure cell disruptor, and their biophysical properties were thoroughly characterized. Hb encapsulation, methemoglobin (metHb) level, O2-PEG-LEH equilibria, PEG-LEH gaseous (oxygen, carbon monoxide, nitric oxide) ligand binding/release kinetics, lipocrit, and long-term storage stability allowed us to examine their potential suitability and efficacy as an RBC replacement. Our results demonstrate that PEG-LEH nanoparticle suspensions manufactured via a high-pressure cell disruptor have Hb concentrations comparable to whole blood (~12 g/dL) and possess other desirable characteristics, which may permit their use as potential lifesaving O2 therapeutics.
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影响因子：
5.8
作者：
Agashe, Hrushikesh;Lagisetty, Pallavi;Awasthi, Shanjana;Awasthi, Vibhudutta
通讯作者：
Awasthi, Vibhudutta
影响因子：
5.6
作者：
CASSOLY, R;GIBSON, QH
通讯作者：
GIBSON, QH
影响因子：
4.1
作者：
Dunne, Jacqueline;Caron, Alexis;Cooper, Chris E.
通讯作者：
Cooper, Chris E.
影响因子：
3.7
作者：
Belcher DA;Banerjee U;Baehr CM;Richardson KE;Cabrales P;Berthiaume F;Palmer AF
通讯作者：
Palmer AF
影响因子：
20.3
作者：
Belcher, John D.;Young, Mark;Vercellotti, Gregory M.
通讯作者：
Vercellotti, Gregory M.