Copolymer Involving 2-Hydroxyethyl Methacrylate and 2-Chloroquinyl Methacrylate: Synthesis, Characterization and In Vitro 2-Hydroxychloroquine Delivery Application.

Abeer Aljubailah,Ahmad Abdulaziz Al-Owais,Saad M S Alqahtani,Ahmed S Haidyrah,Wafa Nazzal Odis Alharbi,Tahani Saad Al-Garni,Abdulnasser Mahmoud Karami,Waseem Sharaf Saeed,Abdelhabib Semlali,Taieb Aouak

doi:10.3390/polym13234072

Abstract

The Poly(2-chloroquinyl methacrylate-co-2-hydroxyethyl methacrylate) (CQMA-co-HEMA) drug carrier system was prepared with different compositions through a free-radical copolymerization route involving 2-chloroquinyl methacrylate (CQMA) and 2-hydroxyethyl methacrylate) (HEMA) using azobisisobutyronitrile as the initiator. 2-Chloroquinyl methacrylate monomer (CQMA) was synthesized from 2-hydroxychloroquine (HCQ) and methacryloyl chloride by an esterification reaction using triethylenetetramine as the catalyst. The structure of the CQMA and CQMA-co-HEMA copolymers was confirmed by a CHN elementary analysis, Fourier transform infra-red (FTIR) and nuclear magnetic resonance (NMR) analysis. The absence of residual aggregates of HCQ or HCQMA particles in the copolymers prepared was confirmed by a differential scanning calorimeter (DSC) and XR-diffraction (XRD) analyses. The gingival epithelial cancer cell line (Ca9-22) toxicity examined by a lactate dehydrogenase (LDH) assay revealed that the grafting of HCQ onto PHEMA slightly affected (4.2–9.5%) the viability of the polymer carrier. The cell adhesion and growth on the CQMA-co-HEMA drug carrier specimens carried out by the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay revealed the best performance with the specimen containing 3.96 wt% HCQ. The diffusion of HCQ through the polymer matrix obeyed the Fickian model. The solubility of HCQ in different media was improved, in which more than 5.22 times of the solubility of HCQ powder in water was obtained. According to Belzer, the in vitro HCQ dynamic release revealed the best performance with the drug carrier system containing 4.70 wt% CQMA.

Highlights

In this work, to increase the solubility of the HCQ base in pH-neutral media and reduce the amount of HCQ released in acidic media, a new monomer (CQMA) involving HCQ and methacryloyl chloride was synthesized via a catalytic esterification reaction
The cell toxicity was examined by the lactate dehydrogenase (LDH) assay on the gingival epithelial cancer cell line (Ca9-22) and the cell adhesion and growth on the Chloroquinyl Methacrylate (CQMA)-co-HEMA drug carrier was examined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test
The chemical structures of the CQMA monomer and CQMA-co-HEMA copolymers were confirmed by Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR) and elemental analyses

Summary

Introduction

To increase the solubility of the HCQ base in pH-neutral media (intestines) and reduce the amount of HCQ released in acidic media (stomach), a new monomer (CQMA) involving HCQ and methacryloyl chloride was synthesized via a catalytic esterification reaction. The new monomer obtained was copolymerized at different ratios. The structures of monomers and copolymers obtained were characterized by the Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR) and CHN elementary analyses. The in vitro dynamic release of the HCQ base from these drug carrier systems occur in different pH media through a retroesterification reaction, in which the influence of the swelling capacity of the drug carrier system, the drug content grafting in the copolymer and pH media are investigated

Methods

Results

Conclusion