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Adv Pharm Bull. 2020;10(2): 221-232.
doi: 10.34172/apb.2020.026
PMID: 32373490
PMCID: PMC7191239
Scopus ID: 85087201154
  Abstract View: 420
  PDF Download: 301

Research Article

All-Trans Retinoic Acid Grafted Poly Beta-Amino Ester Nanoparticles: A Novel Anti-angiogenic Drug Delivery System

Nadia Karimi 1 ORCID logo, Kamaran Mansouri 2 ORCID logo, Mohammad Soleiman-Beigi 1 ORCID logo, Ali Fattahi 3,2,4* ORCID logo

1 Department of Chemistry, Faculty of Basic Sciences, Ilam University, Ilam, Iran.
2 Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
3 Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran.
4 Current affiliation: School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, AZ, USA.
*Corresponding Author: Current affiliation: School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, AZ, USA. Email alifattahi@kums.ac.ir

Abstract

Purpose: 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).

Methods: 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.

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 ATRA-g-PBAE NPs. Anti-angiogenesis 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 ATRA-g-PBAE NPs with inherent anti-angiogenic effects as promising carrier for anticancer drugs with purpose of dual drug delivery.

Keywords: All-trans retinoic acid, Anti-angiogenesis, Nanoparticles, Poly (β-amino ester), Response surface methodology
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Submitted: 19 Jul 2019
Revision: 14 Oct 2019
Accepted: 17 Oct 2019
ePublished: 18 Feb 2020
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