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

Abstract

Hydrogels with the main objective of releasing mesalamine (5-aminosalicylic acid) in the colon in a modified manner were formulated in the present work using a free-radical polymerization approach. Different ratios of hyaluronic acid were cross-linked with methacrylic and acrylic acids using methylenebis(acrylamide). The development of a new polymeric network and the successful loading of drug were revealed by Fourier transform infrared spectroscopy. Thermogravimetric analysis demonstrated that the hydrogel was more thermally stable than the pure polymer and drug. Scanning electron microscopy (SEM) revealed a rough and hard surface which was relatively suitable for efficient loading of drug and significant penetration of dissolution medium inside the polymeric system. Studies on swelling and drug release were conducted at 37 °C in acidic and basic conditions (pH 1.2, 4.5, 6.8, and 7.4, respectively). Significant swelling and drug release occurred at pH 7.4. Swelling, drug loading, drug release, and gel fraction of the hydrogels increased with increasing hyaluronic acid, methacrylic acid, and acrylic acid concentrations, while the sol fraction decreased. Results obtained from the toxicity study proved the formulated system to be safe for biological systems. The pH-sensitive hydrogels have the potential to be beneficial for colon targeting due to their pH sensitivity and biodegradability. Inflammatory bowel disease may respond better to hydrogel treatment as compared to conventional dosage forms. Specific amount of drug is released from hydrogels at specific intervals to maintain its therapeutic concentration at the required level.

Figure 1

FTIR spectra of the polymer (a), initiator (b), monomers AAC (c) and MA (d), cross-linker (e), drug (f), unloaded hydrogel (g), and drug-loaded hydrogel (h).

Figure 2

Thermogravimetric analysis of the polymers (a), drugs (b), and unloaded and loaded hydrogels (c, d).

Figure 3

SEM images of the drug-loaded hydrogel disc.

Figure 4

PXRD analysis of the polymer (a), drug (b), and drug-loaded hydrogels (c).

Figure 5

Sol–gel fraction of the optimized formulation after complete drying.

Figure 6

Swelling indices of hydrogels at pH 1.2 (a), pH 4.5 (b), pH 6.8 (c), and pH 7.4 (d).

Figure 7

Drug release profiles of the formulated hydrogels at pH 1.2 (a), pH 4.5 (b), pH 6.8 (c), and 7.4 (d).

Figure 8

Animals slaughtered for organ extraction for histopathological studies (Photograph courtesy of Syed Faisal Badshah and Huma Liaqat, Copyright 2024).

Figure 9

Histopathology of heart (A, A*): cardiac muscle fibers (a). Colon (B, B*): serosa (a), muscularis externa (b), muscularis mucosa (c), lumen of crypt (d), colonic crypt (e), mucosa (f), and lamina propria (g). Lungs (C, C*): alveolus (a), alveoli (b), blood vessel (c), pulmonary vessel (d), and bronchiole (e). Kidney (D, D*): glomerulus (a), and renal tubules (b). Liver (E, E*): plates of hepatocytes (a), and blood vessels (b). Small intestine (F, F*): small intestinal villi (a), intestinal gland (b), muscularis mucosa (c), serosa (d), and muscularis externa (e). Spleen (G, G*): central arteriole (a), white pulp (b), red pulp (c), and trabecular (d).