Karimi Nadia, Mansouri Kamaran, Soleiman-Beigi Mohammad, Fattahi Ali
Department of Chemistry, Faculty of Basic Sciences, Ilam University, Ilam, Iran.
Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Adv Pharm Bull. 2020 Jun;10(2):221-232. doi: 10.34172/apb.2020.026. Epub 2020 Feb 18.
Developing chemotherapy with nanoplatforms offers a promising strategy for effective cancer treatment. In the present study, we propose a novel all-trans retinoic acid (ATRA) grafted poly beta-amino ester (PBAE) copolymer for preparing nanoparticles (NPs). ATRA grafted PBAE (ATRA-g-PBAE) copolymer was synthesized by grafting ATRA to PBAE; it was characterized by proton nuclear magnetic resonance, Fourier transform infrared, and thermogravimetric analysis. ATRA-g-PBAE NPs were prepared by the solvent displacement method. Design-Expert software was employed to optimize size of NPs. The morphology was evaluated by transmission electron microscope, and ultraviolet-visible spectroscopy was applied for drug release. Cytotoxicity was evaluated toward HUVEC cell line, and the 3D collagencytodex model was used to evaluate anti-angiogenic property of PBAE, ATRA, and NPs. The optimum size of the NPs was 139.4 ± 1.41 nm. After 21 days, 66.09% ± 1.39 and 42.14% ± 1.07 of ATRA were released from NPs at pH 5.8 and 7.4, respectively. Cell culture studies demonstrated antiangiogenic effects of ATRA-g-PBAE NPs. Anti-angiogenesis IC was 0.007 mg/mL for NPs (equal to 0.002 mg/mL of ATRA) and 0.005 mg/mL for free ATRA. This study proposes the ATRA-g-PBAE NPs with inherent anti-angiogenic effects as promising carrier for anticancer drugs with purpose of dual drug delivery.
利用纳米平台开发化疗药物为有效的癌症治疗提供了一种很有前景的策略。在本研究中，我们提出了一种新型的全反式维甲酸（ATRA）接枝聚β-氨基酯（PBAE）共聚物用于制备纳米颗粒（NPs）。通过将ATRA接枝到PBAE上合成了ATRA接枝PBAE（ATRA-g-PBAE）共聚物；通过质子核磁共振、傅里叶变换红外光谱和热重分析对其进行了表征。采用溶剂置换法制备了ATRA-g-PBAE NPs。使用Design-Expert软件优化NPs的尺寸。通过透射电子显微镜评估其形态，并应用紫外可见光谱进行药物释放研究。评估了对人脐静脉内皮细胞系（HUVEC）的细胞毒性，并使用3D胶原凝胶模型评估PBAE、ATRA和NPs的抗血管生成特性。NPs的最佳尺寸为139.4±1.41nm。21天后，在pH 5.8和7.4条件下，分别有66.09%±1.39和42.14%±1.07的ATRA从NPs中释放出来。细胞培养研究证明了ATRA-g-PBAE NPs的抗血管生成作用。NPs的抗血管生成IC50为0.007mg/mL（相当于0.002mg/mL的ATRA），游离ATRA的抗血管生成IC50为0.005mg/mL。本研究提出具有内在抗血管生成作用的ATRA-g-PBAE NPs作为有前景的抗癌药物载体，用于双重药物递送。
