Development and Characterization of a Dual-Drug Thermosensitive Mucoadhesive Hydrogel for the Local Treatment of Pediatric Oral Mucositis

Severe oral mucositis requires local treatments that relieve pain, limit microbial proliferation, and support mucosal repair while minimizing exposure to potentially harmful excipients, particularly in pediatric patients. This study aimed to develop thermosensitive mucoadhesive gels co-loaded with lidocaine hydrochloride (2% w/v) and chlorhexidine digluconate (0.2% w/v) for localized buccal therapy. Poloxamer 407 was combined with hyaluronic acid sodium salt, xanthan gum, Carbopol 934, or hydroxypropylmethylcellulose (HPMC). Formulations containing lidocaine alone or both drugs were compared to assess the influence of chlorhexidine addition. Following preliminary screening based on pH and gelation properties, selected formulations were characterized for technological, mucoadhesive, biopharmaceutical, stability, and antibacterial properties. Poloxamer 407 concentration was the main factor governing gel performance, whereas the mucoadhesive polymer primarily affected specific technological attributes. Chlorhexidine incorporation did not compromise overall gel performance, preserving antibacterial activity. The gels exhibited suitable gelation, spreadability, mucoadhesion, residence time, and release properties with negligible membrane permeation. The dual-drug formulation containing 20% poloxamer 407 and 0.50% HPMC emerged as the most promising one, combining appropriate mechanical properties, drug release, antibacterial efficacy, and storage stability. Overall, these findings support dual-drug thermosensitive mucoadhesive gels as a feasible strategy for the local management of severe oral mucositis, especially in pediatrics.