Multifunctional ^99mTc-5-azacitidine Gold Nanoparticles: Formulation, In Vitro Cytotoxicity, Radiosynthesis, and In Vivo Pharmacokinetic Study.

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY

Current drug delivery Pub Date : 2023-01-01 DOI:10.2174/1567201819666220325092122

Samar S Ezz Eldin, Hassan M Rashed, Amira H Hassan, Heba F Salem, Tamer M Sakr

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引用次数: 2

Abstract

Background: 5-azacitidine is a very potent chemotherapeutic agent that suffers from certain disadvantages.

Objective: This study aims to prepare gold nanoparticles as a new nano-formula of 5-azacitidine that can improve its bioavailability and decrease its side effects.

Methods: 5-azacytidine-loaded GA-AuNPs were prepared and characterized by UV-Vis spectroscopy, infrared (IR), and electronic transmission microscope (TEM). This new platform was characterized in vitro by measuring its zeta potential, particle size, and drug loading efficacy, and the anti-proliferative effect on the MCF-7 cell line was evaluated. In vivo biodistribution studies of ^99mTc-5-aza solution and ^99mTc-5-aza-gold nano formula were conducted in tumor-bearing mice by different routes of administration (intravenous and intra-tumor).

Results: 5-Aza-GA-AuNPs formula was successfully prepared with an optimum particle size of ≈34.66 nm, the zeta potential of -14.4 mV, and high entrapment efficiency. ^99mTc-5-Aza-GA-AuNPs were successfully radiosynthesized with a labeling yield of 95.4%. Biodistribution studies showed high selective accumulation in tumor and low uptake in non-target organs in the case of the 5-Aza-GA-AuNPs formula than the ^99mTc-5-azacitidine solution.

Conclusion: ^99mTc-5-Aza-GA-AuNPs improved the selectivity and uptake of 5-azacitidine in cancer. Moreover, ^99mTc-5-Aza-GA-AuNPs could be used as hopeful theranostic radiopharmaceutical preparation for cancer.

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多功能99mtc -5-阿扎胞苷金纳米颗粒:配方，体外细胞毒性，放射合成和体内药代动力学研究。

背景:5-阿扎胞苷是一种非常有效的化疗药物，但也存在一定的缺点。目的:制备金纳米颗粒作为5-氮杂胞苷的新纳米配方，提高其生物利用度，降低其副作用。方法:制备负载5-氮杂胞苷的GA-AuNPs，并采用紫外可见光谱(UV-Vis)、红外光谱(IR)和透射电镜(TEM)进行表征。通过测定该平台的zeta电位、粒径、载药效能等指标对其进行了体外表征，并对其对MCF-7细胞系的抗增殖作用进行了评价。采用不同给药途径(静脉给药和肿瘤内给药)对99mTc-5-aza溶液和99mTc-5-aza金纳米配方在荷瘤小鼠体内的生物分布进行了研究。结果:成功制备了5-Aza-GA-AuNPs配方，最佳粒径为≈34.66 nm, zeta电位为-14.4 mV，包封效率高。99mTc-5-Aza-GA-AuNPs成功放射性合成，标记率为95.4%。生物分布研究表明，与99mtc -5-阿扎胞苷溶液相比，5-Aza-GA-AuNPs配方在肿瘤中的选择性积累高，在非靶器官中的吸收低。结论:99mTc-5-Aza-GA-AuNPs提高了5-阿扎胞苷在肿瘤中的选择性和摄取。此外，99mTc-5-Aza-GA-AuNPs有望成为治疗癌症的放射性药物制剂。

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来源期刊

Current drug delivery PHARMACOLOGY & PHARMACY-

CiteScore

5.10

自引率

4.20%

发文量

170

期刊介绍： Current Drug Delivery aims to publish peer-reviewed articles, research articles, short and in-depth reviews, and drug clinical trials studies in the rapidly developing field of drug delivery. Modern drug research aims to build delivery properties of a drug at the design phase, however in many cases this idea cannot be met and the development of delivery systems becomes as important as the development of the drugs themselves. The journal aims to cover the latest outstanding developments in drug and vaccine delivery employing physical, physico-chemical and chemical methods. The drugs include a wide range of bioactive compounds from simple pharmaceuticals to peptides, proteins, nucleotides, nucleosides and sugars. The journal will also report progress in the fields of transport routes and mechanisms including efflux proteins and multi-drug resistance. The journal is essential for all pharmaceutical scientists involved in drug design, development and delivery.