Hyaluronic Acid-Based\npH-Sensitive Nanogel: Synthesis,\nCharacterization, and Assessment for Acyclovir Delivery In Vitro and\nIn Vivo

Acyclovir (ACV) is a potentially\neffective antiviral\nmedication;\nhowever, it has a serious drawback, which is its poor solubility,\nbioavailability, and short half-life. The goal of this study is to\nimprove its drawbacks through the synthesis of nanogels. In this study,\nthe cross-linked hyaluronic acid-grafted poly(acrylamide-<i>co</i>-itaconic acid) nanogel is synthesized successfully through free\nradical polymerization and used as a safe pH-responsive carrier for\nACV. The nanogels showed pH response in vitro and in vivo. The prepared\nnanogel C5 (1:1 ratio of acrylamide: itaconic), which had the highest\ngrafting efficiency, showed maximum swelling, drug loading, and release\nin pH 7.4, higher than pH 1.2. Also, nanogel C5, which had a large\nsurface area, showed good stability, and its matrices shrank in acidic\nmedium and protected the drug, while in basic medium, it expanded\nand released ACV in a sustained manner and improved the bioavailability\nand half-life of ACV in vivo.