Biodistribution of Biomimetic Drug Carriers, Mononuclear Cells, and Extracellular Vesicles, in Nonhuman Primates.
Biodistribution of Biomimetic Drug Carriers, Mononuclear Cells, and Extracellular Vesicles, in Nonhuman Primates.
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DOI：
10.1002/adbi.202101293
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发表时间：
2022-03
期刊：
影响因子：
3.7
通讯作者：
Batrakova EV
中科院分区：
文献类型：
--
作者：
Haney MJ;Yuan H;Shipley ST;Wu Z;Zhao Y;Pate K;Frank JE;Massoud N;Stewart PW;Perlmutter JS;Batrakova EV
发现将治疗剂输送到大脑的新型药物递送系统仍然是成功治疗神经退行性疾病的关键任务。在这方面，活细胞、免疫细胞和免疫细胞衍生的细胞外囊泡（EV）具有独特的特征，以避免被网状内皮系统快速清除，穿过生物屏障，靶向具有炎症的疾病组织，并递送其货物。在此，我们研究了生物分布的免疫细胞为基础的载体，外周血单核细胞（PBMC）和单核细胞衍生的EV在成年恒河猴纵向PET/MRI成像。通过不同的给药途径引入64 Cu标记的药物载体：腹膜内（IP）、静脉内（IV）或鞘内（IT）注射。在注射64 Cu标记的药物载体后1h、24 h和48 h获得全身PET/MRI（或PET/CT）图像，并估计主要器官中的标准化摄取值（SUV平均值和SUV最大值）。两种类型的载体的脑保留基于施用途径增加：IP < IV <IT。重要的是，与IT注射EV相比，单次IT注射PBMC产生更高的脑保留。因此，IT注射后48小时PBMC和EV的SUVmax脑值分别为71.5 ± 7.9和25.5 ± 6.9。相比之下，当分别通过IP和IV途径给药时，EV显示出优于细胞的脑蓄积。最后，血液样本的综合化学小组证明任一载体均无细胞毒性作用。总之，这些初步结果表明，活细胞和EV具有用于向大脑递送药物的巨大潜力。在确定理想的药物载体时，给药途径对药物的中枢传递有很大影响，应作为一个重要因素加以考虑。使用纵向PET/MRI成像，评价天然药物载体、活细胞和EV用于将药物递送至恒河猴脑的潜力。所获得的数据表明，最佳的药物递送系统取决于给药途径。较小的载体，如EV，对于全身给药是上级的;较大的载体，如活细胞，对于局部给药是更有利的，因为它们从脑组织中的清除较慢。在这项工作中，我们评估了天然药物载体，免疫细胞和免疫细胞衍生的细胞外囊泡（EV）的潜力，用于药物输送到恒河猴的大脑使用纵向PET/MRI成像。我们在这里报告的第一次，管理途径可以定义最佳的药物输送车辆到大脑。具体而言，当选择全身给药时，较小的载体，如EV是上级的，因为它们能够穿过生物屏障，并且与活细胞相比在脑中以更大的量出现。然而，当选择鞘内给药时，较大的载体（例如细胞）由于其从脑组织的清除率较低而更有利。
Discovery of novel drug delivery systems to transport therapeutics to the brain remains a key task for successful treatment of neurodegenerative disorders. In this regard, living cells, immunocytes, and immunocyte derived extracellular vesicles (EVs) have unique features to avoid rapid clearance by the reticuloendothelial system, cross biological barriers, target disease tissues with inflammation, and deliver their cargo. Herein, we investigated biodistribution of immunocyte-based carriers, peripheral blood mononuclear cells (PBMCs) and monocyte derived EVs in adult rhesus macaques using longitudinal PET/MRI imaging. 64Cu-labeled drug carriers were introduced via different routes of administration: intraperitoneal (IP), intravenous (IV), or intrathecal (IT) injection. Whole body PET/MRI (or PET/CT) images were acquired at 1h, 24h, and 48h post injection of 64Cu-labeled drug carriers, and standardized uptake values (SUVmean and SUVmax) in the main organs were estimated. The brain retention for both types of carriers increased based on route of administration: IP < IV < IT. Importantly, a single IT injection of PBMCs produced higher brain retention compared to IT injection of EVs. Accordingly, SUVmax brain values at 48h post IT injection were 71.5 ± 7.9 and 25.5 ± 6.9 for PBMCs and EVs, respectively. In contrast, EVs showed superior brain accumulation compared to the cells when administered via IP and IV routes, respectively. Finally, a comprehensive chemistry panel of blood samples demonstrated no cytotoxic effects of either carrier. Together, these preliminary results suggest that living cells and EVs have a great potential to be used for drug delivery to the brain. When identifying the ideal drug carrier, the route of administration could make big differences in CNS drug delivery and should be considered as an important factor. Natural drug carriers, living cells and EVs are evaluated for their potential to be employed for drug delivery to the brain in rhesus macaques using longitudinal PET/MRI imaging. The obtained data indicate that the optimal drug delivery system depends on the route of administration. The smaller carriers, such as EVs, are superior for systemic administration; the larger vehicles, such as living cells, are more advantageous for local administration due to their slower clearance from the brain tissues. In this work, we evaluated natural drug carriers, immunocytes, and immunocyte-derived extracellular vesicles (EVs) for their potential to be employed for drug delivery to the brain in rhesus macaques using longitudinal PET/MRI imaging. We report here for the first time that the administration route can define the optimal drug delivery vehicle to the brain. Specifically, when systemic administration is chosen, smaller carriers, such as EVs are superior, as they are able to cross the biological barriers and appear in larger quantities in the brain compared to living cells. However, when intrathecal administration is selected, larger vehicles, such as cells are more advantageous due to their lower clearance from the brain tissues.
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影响因子：
14
作者：
Yuan D;Zhao Y;Banks WA;Bullock KM;Haney M;Batrakova E;Kabanov AV
通讯作者：
Kabanov AV
影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
DOI：
10.1016/j.apsb.2016.02.001
发表时间：
2016-07
期刊：
Acta pharmaceutica Sinica. B
影响因子：
--
作者：
Ha D;Yang N;Nadithe V
通讯作者：
Nadithe V
外泌体作为帕金森氏病疗法的药物。
DOI：
10.1016/j.jconrel.2015.03.033
发表时间：
2015-06-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Haney MJ;Klyachko NL;Zhao Y;Gupta R;Plotnikova EG;He Z;Patel T;Piroyan A;Sokolsky M;Kabanov AV;Batrakova EV
通讯作者：
Batrakova EV
影响因子：
5.4
作者：
Klyachko NL;Arzt CJ;Li SM;Gololobova OA;Batrakova EV
通讯作者：
Batrakova EV