Chemical Biology Unit, Institute of Nano Science and Technology (INST), Sector-81, Knowledge City, Sahibzada Ajit Singh Nagar, Punjab Pin 140306, India.
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P. O. Box 55760, Riyadh 11451, Saudi Arabia.
Int J Biol Macromol. 2021 Dec 1;192:1150-1159. doi: 10.1016/j.ijbiomac.2021.10.028. Epub 2021 Oct 20.
Polymeric nanoparticles (NPs) are the most widely researched nanoformulations and gained broad acceptance in nanotherapeutics for targeted drug delivery and theranostics. However, lack of regulations, guidelines, harmonized standards, and limitations with their employability in clinical circumstances necessitates an in-depth understanding of their toxicology. Here, we examined the in-vivo toxicity of core-shell polymeric NPs made up of gelatin core coated with an outer layer of aminocellulose-grafted polycaprolactone (PCL-AC) synthesized for drug delivery purposes in inflammatory disorders. Nanoparticles were administered intravenously in Swiss albino mice, in multiple dosing (10, 25, and 50 mg/kg body weight) and outcomes of serum biochemistry analysis and histopathology evaluation exhibited that the highest 50 mg/kg administration of NPs altered biochemistry and histopathology aspects of vital organs, while doses of 10 and 25 mg/kg were safe and biocompatible. Further, mast cell (toluidine blue) staining confirmed that administration of the highest dose enhanced mast cell infiltration in tissues of vital organs, while lower doses did not exhibit any of these alterations. Therefore, the results of the present study establish that the NPs disposal in-vivo culminates into alterations in organ structure and function consequences such that lower doses are quite biocompatible and do not demonstrate any structural or functional toxicity while some toxicological effects start appearing at the highest dose.
聚合物纳米粒子（NPs）是研究最广泛的纳米制剂，因其在靶向药物递送和治疗学中的应用而在纳米治疗学中得到广泛认可。然而，由于缺乏法规、指南、统一标准以及在临床情况下的适用性限制，需要深入了解其毒理学。在这里，我们研究了为治疗炎症性疾病而合成的由明胶核和接枝有氨基纤维素的聚己内酯（PCL-AC）外层组成的核壳聚合物 NPs 的体内毒性。将纳米粒子以静脉内方式施用于瑞士白化病小鼠，进行多次给药（10、25 和 50mg/kg 体重），血清生化分析和组织病理学评估的结果表明，最高 50mg/kg 的 NPs 给药改变了重要器官的生化和组织病理学方面，而 10 和 25mg/kg 的剂量是安全且生物相容的。此外，肥大细胞（甲苯胺蓝）染色证实，最高剂量的给药增强了重要器官组织中的肥大细胞浸润，而较低剂量则没有显示出任何这些改变。因此，本研究的结果表明， NPs 在体内的处置最终会导致器官结构和功能的改变，以至于较低剂量具有很好的生物相容性，不会表现出任何结构或功能毒性，而在最高剂量时则开始出现一些毒性作用。
