Designing and In Vitro Characterization of pH-Sensitive Aspartic Acid-Graft-Poly(Acrylic Acid) Hydrogels as Controlled Drug Carriers

Abstract

Acetaminophen is an odorless and white crystalline powder drug, used in the management of fever, pain, and headache. The half-life of acetaminophen is very short; thus, multiple intakes of acetaminophen are needed in a day to maintain a constant pharmacological action for an extended period of time. Certain severe adverse effects are produced due to the frequent intake of acetaminophen, especially hepatotoxicity and skin rashes. Therefore, a drug carrier system is needed which not only prolongs the release of acetaminophen, but also enhances the patient compliance. Therefore, the authors prepared novel aspartic acid-graft-poly(acrylic acid) hydrogels for the controlled release of acetaminophen. The novelty of the prepared hydrogels is based on the incorporation of pH-sensitive monomer acrylic acid with polymer aspartic acid in the presence of ethylene glycol dimethacrylate. Due to the pH-sensitive nature, the release of acetaminophen was prolonged for an extended period of time by the developed hydrogels. Hence, a series of studies was carried out for the formulated hydrogels including sol-gel fraction, FTIR, dynamic swelling, polymer volume analysis, thermal analysis, percent porosity, SEM, in vitro drug release studies, and PXRD analysis. FTIR analysis confirmed the grafting of acrylic acid onto the backbone of aspartic acid and revealed the development of hydrogels. The thermal studies revealed the high thermal stability of the fabricated hydrogels as compared to pure aspartic acid. An irregular surface with a few pores was indicated by SEM. PXRD revealed the amorphous state of the developed hydrogels and confirmed the reduction in the crystallinity of the unreacted aspartic acid by the formulated hydrogels. An increase in gel fraction was observed with the increasing concentration of aspartic acid, acrylic acid, and ethylene glycol dimethacrylate due to the availability of a high amount of free radicals. The porosity study was influenced by the various compositions of developed hydrogels. Porosity was increased due to the enhancement in the concentrations of aspartic acid and acrylic acid, whereas it decreased with the increase in ethylene glycol dimethacrylate concentration. Similarly, the pH-responsive properties of hydrogels were evaluated by dynamic swelling and in vitro drug release studies at two different pH levels (1.2 and 7.4), and a greater dynamic swelling and acetaminophen release were exhibited at pH 7.4 as compared to pH 1.2. An increase in swelling, drug loading, and drug release was seen with the increased incorporation of aspartic acid and acrylic acid, whereas a decrease was detected with the increase in the concentration of ethylene glycol dimethacrylate. Conclusively, the formulated aspartic acid-based hydrogels could be employed as a suitable nonactive pharmaceutical ingredient for the controlled delivery of acetaminophen.

Meso-2,3-dimercaptosuccinic Acid–Based Macromers for pH-Sensitive Degradable Hydrogels

“…The swelling behavior of homogels of macromer PEG-DMSA/Na was also investigated under the same conditions (Figure B). As expected, the swelling degree of hydrogels was higher in water and pH 7.4, due to charge repulsion of the carboxylate groups, compared to those at pH 2 . At pH 2, strong hydrogen bonding between the carboxylic acid groups increases the degree of cross-linking, reducing free volume and leading to shrinkage of the hydrogel network.…”

“…As expected, the swelling degree of hydrogels was higher in water and pH 7.4, due to charge repulsion of the carboxylate groups, compared to those at pH 2. 48 At pH 2, strong hydrogen bonding between the carboxylic acid groups increases the degree of cross-linking, reducing free volume and leading to shrinkage of the hydrogel network. The hydrogels soaked in 0.5 M FeCl 3 displayed the lowest equilibrium SR due to strong Fe 3+ COO − interactions, leading to a double network.…”

Preparation of pH-Responsive Hydrogels Based on Chondroitin Sulfate/Alginate for Oral Drug Delivery

“…Free radical polymerization is the most common method applied for the preparation of hydrogel because no specific pressure and temperature is required for this technique. The process of polymerization and crosslinking occurs very rapidly among the hydrogel contents, which leads to fast gel formation [ 58 ].…”

pH-Sensitive Hydrogels Fabricated with Hyaluronic Acid as a Polymer for Site-Specific Delivery of Mesalamine

“…To determine how hydrogels respond to pH variations, swelling studies in acidic and basic media were performed. Dried hydrogel discs with known masses were dunk in 50 mL of buffer (pH 1.2, 4.5, 6.8, and 7.4) that was provided in containers with clear labels . At various time intervals, swollen discs were removed from their respective solvents, placed on bloating paper to remove any remaining swelling medium, and weighed using an analytical weighing scale to determine the final weight of the discs. .25ex2ex S w e l l i n g .25em i n d e x .25em Q = M normals M normald E q u i l i b r i u m .25em w a t e r .25em c o n t e n t .25em E W C % = M normale normalq − M d M normald × 100 where M d is the initial weight of the dried hydrogel and M s is the weight of the swollen hydrogel disc at time t .…”