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石墨烯量子点纳米颗粒的放射性药代动力学:比较长期和短期的药代动力学参数

Radiopharmacokinetics of Graphene Quantum Dots Nanoparticles : Comparing the Pharmacokinetics Parameters in Long and Short Periods.

作者信息

Bastos Matheus Keuper, Pijeira Martha Sahylí Ortega, de Souza Sobrinho Juliana Helena, Dos Santos Matos Ana Paula, Ricci-Junior Eduardo, de Almeida Fechine Pierre Basilio, Alencar Luciana Magalhães Rebelo, Gemini-Piperni Sara, Alexis Frank, Attia Mohamed Fathy, Santos-Oliveira Ralph

机构信息

Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Laboratory of Nanoradiopharmaceuticals and Synthesis of Novel Radiopharmaceuticals, Rio de Janeiro 21941906, Brazil.

Laboratory of Biosystems, Grande Rio University, Rio de Janeiro, 25071-202, Brazil.

出版信息

Curr Top Med Chem. 2022;22(30):2527-2533. doi: 10.2174/1568026622666220512150625.

Abstract

BACKGROUND

Nanoparticles (NPs) have gained great importance during the last decades for developing new therapeutics with improved outcomes for biomedical applications due to their nanoscale size, surface properties, loading capacity, controlled drug release, and distribution. Among the carbon-based nanomaterials, one of the most biocompatible forms of graphene is graphene quantum dots (GQDs). GQDs are obtained by converting 2D graphene into zero-dimensional graphene nanosheets. Moreover, very few reports in the literature reported the pharmacokinetic studies proving the safety and effectiveness of GQDs for in vivo applications.

OBJECTIVES

This study evaluated the pharmacokinetics of GQDs radiolabeled with Tc, administered intravenously, in rodents (Wistar rats) in two conditions: short and long periods, to compare and understand the biological behavior.

METHODS

The graphene quantum dots were produced and characterized by RX diffractometry, Raman spectroscopy, and atomic force microscopy. The pharmacokinetic analysis was performed following the radiopharmacokinetics concepts, using radiolabeled graphene quantum dots with technetium 99 metastable (99mTc). The radiolabeling process of the graphene quantum dots with 99mTc was performed by the direct via.

RESULTS

The results indicate that the pharmacokinetic analyses with GQDs over a longer period were more accurate. Following a bicompartmental model, the long-time analysis considers each pharmacokinetic phase of drugs into the body. Furthermore, the data demonstrated that short-time analysis could lead to distortions in pharmacokinetic parameters, leading to misinterpretations.

CONCLUSION

The evaluation of the pharmacokinetics of GQDs over long periods is more meaningful than the evaluation over short periods.

摘要

背景

在过去几十年中,纳米颗粒(NPs)因其纳米级尺寸、表面性质、负载能力、可控药物释放和分布等特性,在开发具有更好生物医学应用效果的新疗法方面变得极为重要。在碳基纳米材料中,石墨烯最具生物相容性的形式之一是石墨烯量子点(GQDs)。GQDs是通过将二维石墨烯转化为零维石墨烯纳米片而获得的。此外,文献中很少有报道进行药代动力学研究来证明GQDs在体内应用的安全性和有效性。

目的

本研究评估了静脉注射用锝标记的GQDs在两种情况下(短期和长期)在啮齿动物(Wistar大鼠)体内的药代动力学,以比较和了解其生物学行为。

方法

通过X射线衍射、拉曼光谱和原子力显微镜对石墨烯量子点进行制备和表征。按照放射性药代动力学概念,使用99m锝标记的石墨烯量子点进行药代动力学分析。石墨烯量子点与99mTc的放射性标记过程通过直接途径进行。

结果

结果表明,对GQDs进行更长时间的药代动力学分析更准确。遵循双室模型,长时间分析考虑了药物在体内的每个药代动力学阶段。此外,数据表明,短时间分析可能导致药代动力学参数出现偏差,从而产生误解。

结论

对GQDs进行长时间的药代动力学评估比短时间评估更有意义。

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