The development of thermogelling azithromycin for periodontitis treatment

Abstract

The objective of this study was to develop an efficient dosage form of azithromycin (AZM) for intra-periodontal pocket administration in periodontitis treatment. A niosome system of span 60 (S60) and cholesterol (CHL) was utilized to improve the bioavailability of AZM. AZM-loaded niosome (NAZ) was fabricated by the modified reverse phase evaporation method. The influence of S60 and CHL on physicochemical properties was investigated. The 32 full factorial experimental design was employed. The results indicated that niosome with S60:CHL at the molar ratio of 3:3 exerted nano-sized with adequate charged stability. Controlled release of AZM was achieved for 8 hrs following the zero-order kinetic. NAZ exhibited biocompatibility with low toxicity. NAZ was further developed into the injectable formulation, thermoresponsive AZM-loaded niosome gel (AZG), utilizing poloxamer 407 (P407) and hyaluronic acid (HA) interactions. At the concentration of 19% P407 and 2% HA, AZG exhibited phase transition within the periodontal pocket temperature, acceptable drug content, stability, and injectability with the pseudoplastic flow. Textural properties indicated proper gel strength without interfering with the tissue-repairing process. AZG exhibited bioadhesive to mucosa and tooth structure which aids in the retention time in the pocket. The release was sustained for 3 days with enhanced drug retention in the biological tissue. The gel-state of AZG gradually degraded within 5 days. AZG accelerated cell proliferation contributed to scratch wound closure. AZG showed biocompatibility and antibacterial activity against periodontal pathogens. The anti-inflammatory effects investigation revealed significant decreases in the inflammatory cytokines (IL-1β, TNF-α) expression with the tendency to reduce inflammatory cytokines secretion. The developed AZG provided optimal physicochemical with potential therapeutic properties for intra-periodontal pocket administration for adjunctive periodontitis treatment.