Pilocarpine-loaded hyaluronic acid microneedles promote salivary secretion in non-obese diabetic mice

Patients with Sjögren’s syndrome (SS) often experience severe dry mouth attributed to salivary gland damage. Despite its efficacy, systemic pilocarpine is limited by side effects, while existing local delivery methods (e.g., mouthwashes and sprays) are inconsistent in their efficacy. This study aimed to develop a novel localized delivery system—pilocarpine-loaded hyaluronic acid microneedles (PHMNs)—to overcome the limitations of previous topical approaches by enabling efficient intradermal drug delivery directly to the salivary gland region. The PHMNs, fabricated via a two-step molding process, exhibited robust mechanical strength (1.5 N per needle) for reliable skin penetration and rapid dissolution within 15 min in vivo. In non-obese diabetic mice, a model of SS, the PHMNs stimulated salivary secretion to a level comparable with that achieved by systemic (intraperitoneal or oral) pilocarpine administration. Crucially, pharmacokinetic analysis revealed that the PHMN group maintained significantly lower systemic drug exposure (with no sharp peak and minimal blood concentrations at 30–60 min) than both systemic routes. Furthermore, mice treated with PHMNs for 10 days showed a sustained reduction in daily water intake, indicating effective alleviation of dry mouth symptoms. By combining the precision of intradermal delivery with the biocompatibility of hyaluronic acid, this PHMN system offers a promising, differentiated strategy for managing SS-related xerostomia, providing potent local efficacy while minimizing the risk of systemic side effects associated with conventional pilocarpine therapies.