Synthesis and Characterization of Novel pH-Responsive Aminated Alginate Derivatives Hydrogels for Tissue Engineering and Drug Delivery
Authors: Khodayar Shokouh , Shushizadeh Mohammad Reza , Tahanpesar Elham , Makhmalzadeh Behzad Sharif , Sanaeishoar Haleh 
Published: November 2023

Aims:
The aims of this study are to synthesize new derivatives of sodium alginate that improve the inherent properties, such as hydrogel strengthening, and create environmental sensitivity, such as pH sensitivity, for use in drug delivery

Introduction:
Today, hydrogels, due to outstanding properties such as biodegradability, biocompatibility, me-chanical properties, and response to stimuli properties, are widely used as harmless biomaterials in various fields in drug delivery, wound dressing, and tissue engineering. Stimulus-sensitive polymers significantly respond to slight changes in their environment. Different types of stimuli are used to influence the properties of polymers, the most important of which are temperature and pH because these are two vital factors in the human body; hence, temperature-sensitive and pH-sensitive hydrogels have been extensively studied. The ability to absorb water and swell the hydrogel is due to hydrophilic chains in the hydrogel network, and water absorption by hydrogel can be controlled by response to the stimuli. Since hydrogels mimic human tissue, the ability to retain water in them is essential. As a result, it is considered in many biomedical drug delivery systems. Stimulus-responsive swelling can control diffusion out of and into the hydrogel network, which allows temporal and spatial control of drug release. When a drug is loaded onto a biodegradable and stimuli-sensitive hydrogel, the drug delivery system has the added advantage of sustained release of the drug, which reduces side effects.

Methods:
In this study, two different hydrocarbons, [1,3-diaminopropane (DAP)] as a short-chain hydrocarbon, and [1,7-diaminoheptane (DAH)] as a long-chain hydrocarbon were grafted onto three types of sodium alginate (SA), through amide bond linkages. The hydrogel copolymer matrices were compared with sodium alginate (SA) beads. The graft copolymers were characterized using FTIR, 1HNMR, XRD spectroscopy, elemental analysis (CHNS) and thermal analysis (TGA, DTA and DSC). An environmental scanning electron microscope (ESEM) was used to investigate the surface morphology of hydrogels.

Results:
Effects of variables such as the length of hydrocarbon chains cross-linked to alginate, temperature, pH, and cross-linkers on the properties of hydrogels investigated in the temperature range of 2-70˚C and two different pH values (4.4 and 7.4). The results showed that when the hydrocarbon chain length of diamines decreases, the extent of cross-linking and strength of the hydrogels are increased. Other results suggest that the hydrogels ob-tained from high-viscosity alginate derivatives had positive pH sensitivity. Hydrogels prepared in this study demonstrated good mechanical and swelling ratios that are necessary for wound dressing.

Conclusion:
DAP-g-SA and DAH-g-SA pH-sensitive hydrogels were successfully synthesized through amide bond linkages. The new synthesis derivatives showed lower swelling levels at low pH (4.4). In contrast, their swelling levels at higher pH (7.4) were significantly enhanced. Higher swelling degree could be obtained at high pH. pH-responsive hydrogels are especially useful for various biological applications due to their unique feature of controlled swelling, biodegradability, biocompatibility, and fluid retention in their network structures. pH-responsive hydrogels, as intelligent systems, can be used in controlled-release drug delivery systems such as insulin delivery.