AllTrans Retinoic Acid Grafted Poly BetaAmino Ester Nanoparticles: A Novel Antiangiogenic Drug Delivery System

Purpose: Developing chemotherapy with nanoplatforms offers a promising strategy for effective cancer treatment. In the present study, we propose a novel alltrans retinoic acid (ATRA) grafted poly betaamino ester (PBAE) copolymer for preparing nanoparticles (NPs). Methods: ATRA grafted PBAE (ATRAgPBAE) copolymer was synthesized by grafting ATRA to PBAE; it was characterized by proton nuclear magnetic resonance, Fourier transform infrared, and thermogravimetric analysis. ATRAgPBAE NPs were prepared by the solvent displacement method. DesignExpert software was employed to optimize size of NPs. The morphology was evaluated by transmission electron microscope, and ultravioletvisible spectroscopy was applied for drug release. Cytotoxicity was evaluated toward HUVEC cell line, and the 3D collagencytodex model was used to evaluate antiangiogenic property of PBAE, ATRA, and NPs. Results: 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 ATRAgPBAE NPs. Antiangiogenesis IC50 was 0.007 mg/mL for NPs (equal to 0.002 mg/mL of ATRA) and 0.005 mg/mL for free ATRA. Conclusion: This study proposes the ATRAgPBAE NPs with inherent antiangiogenic effects as promising carrier for anticancer drugs with purpose of dual drug delivery.