Unravelling the Immunotoxicity of Polycaprolactone Nanoparticles—Effects of Polymer Molecular Weight, Hydrolysis, and Blends,Chemical Research in Toxicology

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Unravelling the Immunotoxicity of Polycaprolactone Nanoparticles—Effects of Polymer Molecular Weight, Hydrolysis, and Blends
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2020-10-13 , DOI: 10.1021/acs.chemrestox.0c00208
Sandra Jesus ₁ , Natalia Bernardi ₂ , Jessica da Silva ₂ , Mariana Colaço _{1,

2} , João Panão Costa _{1,

2} , Pedro Fonte _{3,

4,

5} , Olga Borges _{1,

2}

Affiliation

Poly-ε-caprolactone (PCL) is a biodegradable polyester that has FDA and CE approval as a medical device. Nonetheless, the lack of toxicity exhibited by the polymer cannot be extrapolated to its nanomaterial conformation. Despite PCL-based NPs being widely studied in the biomedical field for their advantages as controlled drug delivery systems, little data describe PCL NPs’ toxicity, particularly immunotoxicity. This work assessed different PCL-based delivery systems intended for protein delivery regarding their immunotoxicity and hemocompatibility. Two different molecular weight PCL polymers were used, as well as blends with chitosan and glucan. Results showed that the presence of NaOH during the production of PCL₂ NPs and PCL₂/glucan NPs induced PCL alkali hydrolysis, generating more reactive groups (carboxyl and hydroxyl) that contributed to an increased toxicity of the NPs (higher reduction in peripheral blood mononuclear cell viability and lower hemocompatibility). PCL₂/glucan NPs showed an anti-inflammatory activity characterized by the inhibition of LPS stimulated nitric oxide (NO) and TNF-α. In conclusion, generalizations among different PCL NP delivery systems must be avoided, and immunotoxicity assessments should be performed in the early stage of product development to increase the clinical success of the nanomedicine.

中文翻译：

揭示聚己内酯纳米颗粒的免疫毒性——聚合物分子量、水解和共混物的影响

聚-ε-己内酯 (PCL) 是一种可生物降解的聚酯，已获得 FDA 和 CE 批准作为医疗器械。尽管如此，聚合物表现出的无毒性不能外推到其纳米材料构象。尽管基于 PCL 的 NPs 因其作为受控药物递送系统的优势而在生物医学领域被广泛研究，但很少有数据描述 PCL NPs 的毒性，尤其是免疫毒性。这项工作评估了用于蛋白质递送的不同基于 PCL 的递送系统的免疫毒性和血液相容性。使用了两种不同分子量的 PCL 聚合物，以及与壳聚糖和葡聚糖的混合物。结果表明，在 PCL ₂ NPs 和 PCL ₂生产过程中 NaOH 的存在/glucan NPs 诱导 PCL 碱水解，产生更多的反应性基团（羧基和羟基），导致 NPs 的毒性增加（外周血单核细胞活力降低更多，血液相容性降低）。PCL ₂ /葡聚糖纳米颗粒显示出抗炎活性，其特征在于抑制 LPS 刺激的一氧化氮 (NO) 和 TNF-α。总之，必须避免不同 PCL NP 递送系统之间的泛化，并且应在产品开发的早期阶段进行免疫毒性评估，以提高纳米药物的临床成功率。

更新日期：2020-11-16

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