Thermoresponsive Azithromycin-Loaded Niosome Gel Based on Poloxamer 407 and Hyaluronic Interactions for Periodontitis Treatment

Azithromycin (AZM) is a potential antimicrobial drug for periodontitis treatment. However, a potential sustained-release system is needed for intra-periodontal pocket delivery. This study focused on the development and evaluation of a thermoresponsive azithromycin-loaded niosome gel (AZG) to search for a desirable formulation for periodontitis treatment. AZG was further developed from an AZM-loaded niosomal formulation by exploiting the advantages of poloxamer 407 (P407) and hyaluronic acid (HA) interactions. The results showed that the addition of HA decreased the gelation temperature and gelation time of AZG. HA was found to increase the viscosity as well as mucoadhesive and tooth-root surface adhesive properties. The AZG solution state was injectable and exhibited pseudoplastic shear-thinning behavior. P407-HA interactions in AZG could contribute to gel strength. AZG showed 72 h of continuous drug release following the Korsmeyer-Peppas model and potentially enhanced drug permeation. The formulations apparently presented more efficient antibacterial activity against major periodontal pathogens than the standard AZM solution. AZM intra-periodontal pocket formulation and the remarkable properties of niosomes exhibited potential characteristics, including ease of administration, bioadhesion to the anatomical structure of the periodontal pocket, and sustained drug release with competent antimicrobial activity, which could be beneficial for periodontitis treatment.