Abstract
A significant obstacle to the healing process of periodontitis is the development of bacterial biofilms within the periodontal pockets. The efficacy of bacterial biofilm therapy is often hindered by the inadequate penetration of antibacterial agents and the nonspecific targeting of bacteria. This study proposes a novel strategy involving the utilization of pH-sensitive microparticles (MPs) of doxycycline (DOX) to enhance biofilm penetration and enable targeted delivery of DOX to infection sites associated with periodontitis. The MPs were developed using a double-emulsion technique with poly(d,l-lactide-co-glycolide) and chitosan in a 1:1 ratio. The morphology of DOX-MP exhibits a spherical form with a particle size of 3.54 ± 0.32 μm and a PDI of 0.221 ± 0.02. The DOX-MP also had great encapsulation efficiency (69.43% ± 5.32) and drug loading efficiency (14.81% ± 1.32) with regulated drug release kinetics and accelerated release rates under low-pH conditions. The antimicrobial activity was evaluated against Escherichia coli and Staphylococcus aureus, and the results indicated the absence of any viable bacterial colonies after 18 h at twice the minimum inhibitory concentration value. Hydrogel-based MPs deliver DOX to the periodontal pocket infection site for ease of use. In situ hydrogels used Pluronic F127 and F68 as the main polymer composition and hydroxypropyl methylcellulose as the adhesion polymer. This formulation exhibited a liquid state at room temperature (25 °C) but went through gelation at 36 °C. The formulation also had good mucoadhesive characteristics (42.65 ± 3.53 dyn/cm(2)) and good drug permeation at acidic pH in Mueller-Hinton Broth media with the addition of E. coli and S. aureus bacteria. Ex vivo antibacterial activity significantly reduced the microbial count, biofilm quantity, and metabolic activity, confirming the desired antibacterial effect. Hence, the utilization of free drugs and DOX-MPs did not exhibit a notable dissimilarity, showing that integrating the drug into the matrix was not hindering its antibacterial efficacy.