Molecular Weight-Dependent Diffusion, Biodistribution, and Clearance Behavior of Tetra-Armed Poly(ethylene glycol) Subcutaneously Injected into the Back of Mice.

Molecular Weight-Dependent Diffusion, Biodistribution, and Clearance Behavior of Tetra-Armed Poly(ethylene glycol) Subcutaneously Injected into the Back of Mice.
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DOI:
10.1021/acsmacrolett.3c00044
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发表时间:
2023-04-18
期刊:
影响因子:
7.015
通讯作者:
Sakai, Takamasa
Sakai, Takamasa
中科院分区:
化学1区
文献类型:
--
作者:
Ishikawa, Shohei;Kato, Motoi;Si, Jinyan;Chenyu, Lin;Kimura, Kohei;Katashima, Takuya;Naito, Mitsuru;Kurita, Masakazu;Sakai, Takamasa

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四臂聚乙二醇(PEG)是一种重要的亲水聚合物,广泛用于制备PEG水凝胶,是一种有价值的组织支架材料。当水凝胶在体内使用时,它们最终由于骨干结构的裂解而解离。当解理发生在交联点时,水凝胶作为原始聚合物单元,即四臂PEG洗脱。虽然四臂聚乙二醇已被用作皮下植入的生物材料,但四臂聚乙二醇在皮肤中的扩散、生物分布和清除行为尚不完全清楚。本文研究了荧光标记的分子量(Mw)在5-40 kg/mol之间的四臂聚乙二醇(peg)在小鼠背部皮下注射后从皮肤的时间扩散、到远处器官的生物分布和清除。随时间的变化表明,皮下注射peg的命运是mw依赖的。Mw≤10 kg/mol的四臂peg逐渐扩散到注射部位下方的深层脂肪组织,并主要分布到远端器官,如肾脏。分子量≥20 kg/mol的peg滞留在皮肤和深层脂肪组织中,主要传递到心脏、肺和肝脏。对四臂聚乙二醇分子量依赖性行为的基本认识有助于利用聚乙二醇制备生物材料,为组织工程领域提供参考。
Four-armed poly(ethylene glycol) (PEG)s are essential hydrophilic polymers extensively utilized to prepare PEG hydrogels, which are valuable tissue scaffolds. When hydrogels are used in vivo, they eventually dissociate due to cleavage of the backbone structure. When the cleavage occurs at the cross-linking point, the hydrogel elutes as an original polymer unit, i.e., four-armed PEG. Although four-armed PEGs have been utilized as subcutaneously implanted biomaterials, the diffusion, biodistribution, and clearance behavior of four-armed PEG from the skin are not fully understood. This paper investigates time-wise diffusion from the skin, biodistribution to distant organs, and clearance of fluorescence-labeled four-armed PEGs with molecular weight (Mw) ranging from 5–40 kg/mol subcutaneously injected into the back of mice. Changes over time indicated that the fate of subcutaneously injected PEGs is Mw-dependent. Four-armed PEGs with Mw ≤ 10 kg/mol gradually diffused to deep adipose tissue beneath the injection site and distributed dominantly to distant organs, such as the kidney. PEGs with Mw ≥ 20 kg/mol stagnated in the skin and deep adipose tissue and were mainly delivered to the heart, lung, and liver. The fundamental understanding of the Mw-dependent behavior of four-armed PEGs is beneficial for preparing biomaterials using PEGs, providing a reference in the field of tissue engineering.
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