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Phase Inversion-Induced Rosin In Situ Forming Matrix Using Various Organic Biocompatible Solvents for Periodontitis Treatment

In situ forming matrix (ISM) is an injectable drug delivery system containing a drug-loaded polymeric solution. It was applied for local drug administration such as into a periodontal pocket for periodontitis treatment with an antimicrobial agent. ISM can transform with phase inversion into the solid-like matrix after contact an aqueous environment by solvent exchange mechanism. This study aims to develop ISM which various concentrations of rosin (R) as matrix former dissolved in organic biocompatible and biodegradable solvents such as N-methyl-2-pyrrolidone, dimethyl sulfoxide and 2-pyrrolidone. Physicochemical characterization and matrix formation behavior owing to phase inversion of R ISM were evaluated including pH, density, viscosity, contact angles, surface tension, expelling force through a syringe, matrix formation behavior and morphological change. The density of all R ISM exhibited in the range of 1.03-1.11 g/cm3 and contact angles (9.04-44.13°) indicated a good wetting property. Higher R concentration decreased pH of ISM owing to increased amount of abietic and pimaric acid from R while the viscosity, contact angles and force for expelling a syringe were increased. The viscosity of R ISM in dimethyl sulfoxide was less than that in 2-pyrrolidone; thus, ISM using dimethyl sulfoxide as a solvent exhibited good injectability. ISM comprising R concentration > 30%w/w promoted a faster matrix growth in which the amount of occurred R matrix was enhanced with time and the rate of matrix formation was lower with time. Doxycycline Hyclate (Dx)-loaded 40%w/w ISM in dimethyl sulfoxide (Dx-DR) had pH of 3.70, density of 1.1084 ± 0.0005 g/ml, viscosity of 35.72 ± 0.00 cPs, contact angles of 26.87 ± 2.40°, surface tension of 37.11 ± 0.11 mN/m and expelling force of 23.98 ± 0.18 N. It showed the sustainable Dx release in simulated crevicular fluid and the efficient antimicrobial activity against Staphylococcus aureus and Porphyromonas gingivalis. Thus, this phase inversion induced R ISM using dimethyl sulfoxide as a solvent showed potential as an antimicrobial agent-loaded drug delivery system for periodontitis treatment.