Chlorhexidine-loaded microneedles for treatment of oral diseases

Chlorhexidine (CHX) is a gold standard therapeutic agent against clinical oral pathogens. However, its oral use is limited due to unpleasant taste, alteration in taste buds, staining of teeth and mucous membranes. Therefore, CHX-loaded PLGA microneedles (MNs) were fabricated for local and controlled release in the oral cavity, using a casting mold method. The MNs were well-formed with sharp MN tips and flat baseplates, showing quadrangular pyramidal shapes with average needle height and base width of about 500 and 200 µm, respectively. CHX was successfully incorporated into the PLGA-based MNs, exhibiting high encapsulation efficiency. CHX-PLGA MNs were further characterized in terms of ATR-FTIR and DSC, indicating intermolecular interactions between CHX and PLGA. In vitro CHX release exhibited an initial burst release within the first 24 h, accompanied by a slower release rate, reaching cumulative release of ca. 56 % after 10 days. The antibacterial effect of CHX-PLGA MNs on Streptococcus mutans (S. mutans) was evaluated using different techniques. In agar diffusion assay, the MNs displayed sustained antimicrobial activity over 8 days, while they significantly reduced the bacterial growth of S. mutans on the first 4 days in a planktonic experimental setup. No antibacterial effect was recorded for the blank PLGA MNs that served as a control group. Interestingly, CHX-PLGA MNs eliminated biofilm formation and metabolic activity for 3 days compared with biofilm formed in the presence of blank MNs. Then, a rebound effect was recorded. A weak antibiofilm effect and anti-metabolic activity was observed when MNs tested against pre-formed biofilm. Taken together, CHX-PLGA MNs hold promise as a viable delivery modality for localized and sustained antimicrobial activity in the oral cavity. Further research is required to optimize the formulation and assess efficacy and safety in clinical settings.