Synthesis and Characterization of Poly (β-amino Ester) and Applied PEGylated and Non-PEGylated Poly (β-amino ester)/Plasmid DNA Nanoparticles for Efficient Gene Delivery

Sajid Iqbal; Alessandro F Martins; Muhammad Sohail; Jingjing Zhao; Qi Deng; Muhan Li; Zhongxi Zhao

doi:10.3389/fphar.2022.854859

Synthesis and Characterization of Poly (β-amino Ester) and Applied PEGylated and Non-PEGylated Poly (β-amino ester)/Plasmid DNA Nanoparticles for Efficient Gene Delivery

Front Pharmacol. 2022 Apr 8:13:854859. doi: 10.3389/fphar.2022.854859. eCollection 2022.

Authors

Sajid Iqbal¹, Alessandro F Martins^{2

3

4}, Muhammad Sohail⁵, Jingjing Zhao¹, Qi Deng¹, Muhan Li¹, Zhongxi Zhao^{1

6

7

8}

Affiliations

¹ Department of Pharmaceutics, Key Laboratory of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
² Laboratory of Materials, Macromolecules, and Composites (LaMMAC), Federal University of Technology - Paraná (UTFPR), Apucarana, Brazil.
³ Group of Polymers and Composite Materials (GMPC), Department of Chemistry, State University of Maringá (UEM), Maringá, Brazil.
⁴ Department of Chemical and Biological Engineering, Colorado State University (CSU), Fort Collins, CO, United States.
⁵ Key Laboratory of Molecular Pharmacology and Drug Evaluation, Yantai University, Yantai, China.
⁶ Key University Laboratory of Pharmaceutics and Drug Delivery Systems of Shandong Province, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
⁷ Pediatric Pharmaceutical Engineering Laboratory of Shandong Province, Shandong Dyne Marine Biopharmaceutical Company Limited, Rongcheng, China.
⁸ Chemical Immunopharmaceutical Engineering Laboratory of Shandong Province, Shandong Xili Pharmaceutical Company Limited, Heze, China.

Abstract

Polymer-based nanocarriers require extensive knowledge of their chemistries to learn functionalization strategies and understand the nature of interactions that they establish with biological entities. In this research, the poly (β-amino ester) (PβAE-447) was synthesized and characterized, aimed to identify the influence of some key parameters in the formulation process. Initially; PβAE-447 was characterized for aqueous solubility, swelling capacity, proton buffering ability, and cytotoxicity study before nanoparticles formulation. Interestingly, the polymer-supported higher cell viability than the Polyethylenimine (PEI) at 100 μg/ml. PβAE-447 complexed with GFP encoded plasmid DNA (pGFP) generated nanocarriers of 184 nm hydrodynamic radius (+7.42 mV Zeta potential) for cell transfection. Transfection assays performed with PEGylated and lyophilized PβAE-447/pDNA complexes on HEK-293, BEAS-2B, and A549 cell lines showed better transfection than PEI. The outcomes toward A549 cells (above 66%) showed the highest transfection efficiency compared to the other cell lines. Altogether, these results suggested that characterizing physicochemical properties pave the way to design a new generation of PβAE-447 for gene delivery.

Keywords: biodegradable polymer; gene delivery; poly (β-amino ester); stable polyplexes; transfection.