Chitosan is a linear aminopolysaccharide of glucoseamine and N-acetyl glucosamine units, and it is can be obtained by alkaline acetylation of chitin extracted from cell walls of some fungi and another sources [1,4].
The consecutive characteristics of chitosan make it is polymer with many advantages for various application. Chitosan physically and biologically functional, it is biodegradable and biocompatible with many organs, cells, and tissues.
Likewise, chitosan was biodegradable, non-toxic, and antimicrobial properties, so chitosan is popular as antimicrobial agent either alone or blended with other natural polymers [5-7].
Chitosan hydrogels were classified into (chemical and physical) hydrogels for chemical hydrogels formed by irreversible covalent bonds, while physical hydrogels were constituted by various irreversible bonds [8,9].
To determine chemical structure, it can be chemically and enzymatically modified. The modification of chitosan can be materialized into physical and chemical processes to develop the mechanical and chemical properties. Chitosan is a multinucleophilic polymer because of the presence of amino group at C-2 and hydroxyl groups at C-3 and C-6 in the GICN residue. Chitosan membrane is swollen in water and amino groups were protonated and left hydroxide ions free in water, which can add to the ionic conduction in the membrane .
Tertiary-Butyl acrylate is a simple organic compound that contains (C, H, and O) inside its structure . It is a mono functional monomer with a characteristic high reactivity of acrylates and a bulky hydrophobic residue, also a very useful feed stock for chemical syntheses and because it is readily undergo to a different reactions with a wide variety of organic and inorganic compounds [13-18].
Tertiary-Butyl acrylate (TBA) is one of the fuel oxygenates used to replace tetra ethyl lead as anti-knock agent in gasoline alone or with methanol as co-solvent .
In this work, new prodrug polymer was synthesized based on chitosan and investigate some applications. First, amoxicillin prodrug polymer H1 and diclofenac sodium prodrug polymer H2 were synthesized by reaction of chitosan and tertiary-butyl acrylate. Drug release of these polymers was investigated.
Melting points were measured using thermal microscope (Kofler-method). Infrared spectro photometer measurements were performed by Bruker FT-IR. FT-IR was obtained in absorption range 400-4000 cm-1 by Brucker FT-IR. UV-Visible measurements were double beam scanning spectro photometer varian at room temperature. All chemicals were purchased from CDH, Merck, Alfa, BDH, and all other chemicals were used without farther purification. Differential scanning calorimetric analysis was performed in (BAHR, Germany). 1H-NMR was measured by Brucker 400 MHz, switzer land. In addition, swelling percentage, viscosity, and solubility were measured. Both controlled drug released and biological activity of prodrug polymers were studied.
Synthesis of amoxicillin prodrug polymer H1
1 g of chitosan (0.00065 mol) was dissolved in 25 mL of glycial acetic acid and 1 g of tertiary-butyl acrylate (0.0078 mol) dissolved in 25 mL of distilled water, the mixture of both of them were mixed in around bottom flask (50 mL) and heated at 55 for 45 min, and then 1 g of amoxicillin was added to the mixture in round flask and 10 drops of SOCl2 and refluxed with stirring about 1 hat 55 . The colored solution was collected and washed with diethyl ether three times and dried at room temperature (Scheme 1).
Synthesis of diclofenac sodium prodrug polymer H2
A mixture of 1 g of chitosan (0.00065 mol) after it is dissolving in glycial acetic acid was putted in a beaker and mixed with 1 g of tertiary butyl acrylate (0.0078 mol). After that, the mixture above was placed in around bottom flask equipped with condenser and magnetic stirrer, and then 1 g of diclofenac sodium was added to the mixture also 10 drops of thionyl chloride was added gradually to round flask and refluxed for 1 h. The product was left one day and washed three times with suitable solvent diethyl ether to collect pure polymer (Scheme 1).
Results and discussion
The structure of polymer prodrugs (H1 and H2) was analyzed with FT-IR spectrum and 1H-NMR spectrum after synthesis of polymer prodrugs.
FT-IR spectrum of H1 was displayed in the Figure 1. Absorption peak of NH groups was appeared in the 3326.26 cm-1. Absorption peak of C=O amide was appeared in about 1655.00 cm-1. The main peak of H2 was appeared in 3323.54 cm-1 (NH) as a sharp peak and carbonyl peak appeared in the 1695.07 cm-1 (Figure 2).
The 1H-NMR spectrum for H1 and H2 polymers was illustrated in the Figures 3 and 4. The signal about 1-1.5 ppm is for CH3 protons and the signal about 2 ppm is related to CH2 protons. Also, the signal about 2.5 ppm to DMSO is considered as a suitable solvent for achieving the spectroscopic measurements, so the signal appears of 3-4 ppm is indicated for carboxylate group, and 6.99 is marked to aromatic ring, and for an amide group the signal is appear about 7-7.99 ppm. While 1H-NMR spectrum of polymer H2 in the Figure 3 consists of many signs the first signal in the range 1.5-2.0 ppm to indicate the protons of CH3 and the signal about 2.5 for DMSO as a solvent for the spectrum measurements. In addition, the signal 3-4 ppm is for an ester group, and the signal in 6.93 ppm, on the other hand 7.20-7.53 ppm signal in for an aromatic ring and the range signal about 12.63 ppm is related to carboxylic group.
DSC and TGA analyzed for synthesized H1-H2 were indicated that the polymers have good thermal stability (Figures 5 and 6).
Viscosity of polymers
The physical properties of synthesized polymers were illustrated as presented in the Table 1. Viscosity of polymers measured 0.86 and 0.69 dl/g for H1 and H2, respectively.
Solubility of polymers in different organic solvents
Solubility of H1 and H2 polymers was measured in different solvents (polar and non-polar) and there results were indicated in the Table 2. According to Table 2, both of the polymers H1, H2 were completely soluble in all solvents according to polar groups in these prodrugs and to achieve the chemical rule "like dissolve like".
Through dissolving 0.1 g of each polymer in 50 mL distilled water, the swelling percentage was determined.
Each polymer was left to soak for 1 h at 25 , the hydrogel was separated from the bath, blotted with filter paper to extract surface water, and also swelling percentage was calculated by following equations.
The results of the swelling percentage of prepared polymer (H1- H2) were obtained 10 % and 12%, respectively (Table 3).
Release of drug
Drug release of prodrug polymers was be measured in three different pH acidic functions for solutions (pH=2, 7, and 8) at 37 using a UV-Visible spectro photometer, as demonstrated in Table 4 and Figures 7-9. From the obtained results, these polymers H1 and H2 appear good drug release in a basic medium for an ester bond of polymers as compared with amide bond of the other polymer.
New prodrug polymers were based on chitosan- drug was prepared through an esterification reaction. Their structures of polymer have been confirmed using FT-IR, 1H-NMR spectroscopy, and TGA analyze. These polymers show good drug release in basic medium for ester bond as compared with amide bond of the second polymer H1, respectively.
The financial support for this research was provided by Ministry of Higher Education Malaysia under FRGS Grant no. 2019-0147-103-02.
Conflict of Interest
The authors declare that there is no conflict of interest.
Wisam Abdul Jaleel Jawad: https://orcid.org/0009-0002-1267-4857
Faris H. Mohammed: https://orcid.org/0000-0002-4725-2569
How to cite this article: Wisam Abdul Jaleel Jawad *, Faris H. Mohammed. Synthesis and Characterization of some new prodrug polymer based on chitosan with tertiary-butyl acrylate and study some application. Eurasian Chemical Communications, 2023, 5(9), 842-851. Link: https://www.echemcom.com/article_172139.html
Copyright © 2023 by SPC (Sami Publishing Company) + is an open access article distributed under the Creative Commons Attribution License(CC BY) license (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.