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

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

doi:10.3390/polym13234072

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

Polymers (Basel). 2021 Nov 23;13(23):4072. doi: 10.3390/polym13234072.

Affiliations

¹ Department of Chemistry, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13623, Saudi Arabia.
² Nuclear and Radiological Control Unit, King Abdulaziz City for Science and Technology (KACST), Riyadh 11442, Saudi Arabia.
³ Chemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
⁴ Engineer Abdullah Bugshan Research Chair for Dental and Oral Rehabilitation, College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia.
⁵ Groupe de Recherche en Écologie Buccale, Faculté de Médecin Dentaire, Université Laval, Quebec City, QC G1V 0A6, Canada.

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.

Keywords: 2-chloroquinyl methacrylate; drug carrier system; in vitro 2-hydroxychloroquine release; poly(2-chloroquinyl methacrylate-co-2-hydroxyethyl methacrylate); preparation and characterization.