Introduction: Nanoparticles (NPs), as drug delivery systems, appear to be a promising tool for prolonged therapeutic strategies as they allow a controlled drug release over time. However, most of the studies found in the literature simply contemplate the use of a single or low number of dosages with low NPs concentrations. In the context of chronic diseases, like Alzheimer’s disease, cancer or human immunodeficiency virus (HIV), where the therapeutic scheme is also chronic, studies with numerous repeated dosages are often neglected.
Methods: We screened different NPs, polymeric and lipid-based, in a repeated-dose toxicity study, to evaluate the safety and tissue distribution of promising nanocarriers to be used in the treatment of long-lasting diseases.
Results: After administrating 24 high concentrated doses of the selected NPs intraperitoneally (i.p.) (3 times a week for 2 months), animals have presented NPs accumulation in different tissues. However, neither toxicity, bodyweight changes nor clinical signs of disease were observed.
Discussion: This work demonstrates no general adverse effects upon the studied NPs repeated-dose exposure, indicating the most promising NPs to be used in the different therapeutic circumstances, which may be useful in chronic diseases treatment.

Keywords: long-lasting treatment, drug delivery systems, nanocarriers, liposomes, solid lipid nanoparticles, PLGA nanoparticles


中文翻译：

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聚合物和脂质基纳米颗粒的体内生物分布和毒性评估：慢性病治疗的潜在方法

简介：纳米粒子 (NPs) 作为药物输送系统，似乎是一种有前途的工具，可用于延长治疗策略，因为它们允许随着时间的推移控制药物释放。然而，文献中发现的大多数研究只是考虑使用单一或少量的剂量和低 NPs 浓度。在慢性疾病的背景下，如阿尔茨海默病、癌症或人类免疫缺陷病毒 (HIV)，治疗方案也是慢性的，许多重复剂量的研究往往被忽视。
方法：我们在重复剂量毒性研究中筛选了基于聚合物和脂质的不同 NP，以评估用于治疗长期疾病的有希望的纳米载体的安全性和组织分布。
结果：在腹膜内（ip）（每周 3 次，持续 2 个月）施用 24 次高浓度的选定 NPs 后，动物在不同组织中出现了 NPs 积累。然而，未观察到毒性、体重变化或疾病的临床症状。
讨论：这项工作表明对所研究的 NPs 重复剂量暴露没有一般的不利影响，表明最有希望的 NPs 可用于不同的治疗环境，这可能对慢性病治疗有用。

关键词：长效治疗，药物递送系统，纳米载体，脂质体，固体脂质纳米粒，PLGA纳米粒