Gregory T. Zugates
Alivio Therapeutics, Inc., 501 Boylston St. Suite 6102, Boston, MA 02116, USA
The use of drug therapies to treat chronic inflammatory diseases is often limited by their short duration of action or dose-dependent side effects. To overcome these challenges, an inflammation-targeting hydrogel drug delivery system was previously developed that binds to inflamed tissue, releases drug in response to upregulated enzymes, and enhances the therapeutic effect of a corticosteroid for ulcerative colitis. Here, we demonstrate the applicability of this technology to treat pain associated with interstitial cystitis, a chronic inflammatory condition of bladder. Self-assembled ascorbyl palmitate hydrogel with encapsulated lidocaine (9.4% wt/wt) was prepared and tested in a rat cyclophosphamide model of cystitis. Our results demonstrate a significantly prolonged analgesic effect following instillation of the lidocaine-loaded gel compared to free lidocaine, as determined by measuring the median nociceptive threshold for both groups at 2 and 24 hours post-instillation. Furthermore, the nociceptive threshold for the lidocaine-loaded gel was not statistically different from that measured in naïve rats, suggesting that the lidocaine-loaded gels alleviated pain over the full 24-hour duration of the study. Collectively, these results suggest that our hydrogel drug delivery system can be developed into local, long-acting therapies for interstitial cystitis and other chronic inflammatory diseases.
Keywords: Inflammation-targeting, hydrogel, drug delivery, interstitial cystitis.