Bakhaidar Rana, O'Neill Sarah, Ramtoola Zebunnissa
School of Pharmacy and Biomolecular Sciences, RCSI, University of Medicine and Health Sciences, D02 YN77 Dublin 2, Ireland.
Int J Mol Sci. 2020 Dec 19;21(24):9716. doi: 10.3390/ijms21249716.
The expansion of nanotechnology for drug delivery applications has raised questions regarding the safety of nanoparticles (NPs) due to their potential for interacting at molecular and cellular levels. Although polymeric NPs for drug delivery are formulated using FDA-approved polymers such as lactide- and glycolide-based polymers, their interactions with blood constituents, remain to be identified. The aim of this study was to determine the impact of size-selected Poly-lactide-co-glycolide-polyethylene glycol (PLGA-PEG) NPs on platelet activity. The NPs of 113, 321, and 585 nm sizes, were formulated and their effects at concentrations of 0-2.2 mg/mL on the activation and aggregation of platelet-rich plasma (PRP) were investigated. The results showed that NPs of 113 nm did not affect adenosine diphosphate (ADP)-induced platelet aggregation at any NP concentration studied. The NPs of 321 and 585 nm, at concentrations ≥0.25 mg/mL, reduced ADP-activated platelet aggregation. The platelet activation profile remained unchanged in the presence of investigated NPs. Confocal microscopy revealed that NPs were attached to or internalised by platelets in both resting and activated states, with no influence on platelet reactivity. The results indicate minimal risks of interference with platelet function for PLGA-PEG NPs and that these NPs can be explored as nanocarriers for targeted drug delivery to platelets.
用于药物递送应用的纳米技术的扩展引发了有关纳米颗粒(NPs)安全性的问题,因为它们有可能在分子和细胞水平上发生相互作用。尽管用于药物递送的聚合物纳米颗粒是使用美国食品药品监督管理局(FDA)批准的聚合物(如丙交酯和乙交酯基聚合物)配制而成,但其与血液成分的相互作用仍有待确定。本研究的目的是确定尺寸选择的聚乳酸-共-乙醇酸-聚乙二醇(PLGA-PEG)纳米颗粒对血小板活性的影响。制备了尺寸为113、321和585 nm的纳米颗粒,并研究了它们在0-2.2 mg/mL浓度下对富血小板血浆(PRP)激活和聚集的影响。结果表明,在所研究的任何纳米颗粒浓度下,113 nm的纳米颗粒均不影响二磷酸腺苷(ADP)诱导的血小板聚集。321和585 nm的纳米颗粒在浓度≥0.25 mg/mL时,可降低ADP激活的血小板聚集。在所研究的纳米颗粒存在下,血小板激活谱保持不变。共聚焦显微镜显示,纳米颗粒在静息和激活状态下均与血小板结合或被血小板内化,对血小板反应性无影响。结果表明,PLGA-PEG纳米颗粒对血小板功能的干扰风险极小,并且这些纳米颗粒可作为纳米载体用于靶向药物递送至血小板。