pH-triggered release of chlorhexidine and doxycycline by casein-coated calcium carbonate microparticles for oral health applications

Dental diseases present a significant global health challenge, affecting individuals across all age groups. This spectrum of oral health issues causes conditions like dental caries, gum disease, and oral infections. The selection of the antiseptic for this research was guided by feedback from potential customers, gathered through interviews conducted during the NSF I-Corps program. During these customer discovery interviews, dental patients expressed concerns about drug overexposure during and after procedures, citing fears of adverse effects, allergic reactions, and the rising prevalence of antibiotic and anesthesia use. Reducing the use of chlorhexidine, one of the most commonly used antiseptics in dentistry, due to its potential side effects such as tooth staining and taste alteration was emphasized by periodontists. Additionally, dentists highlighted a growing emphasis on reducing opioid and steroid-based medications due to their associated side effects and addiction risks. This study explores an innovative approach to targeted drug delivery in the dental environment using eco-friendly and non-toxic CaCO 3 microparticles (CCMPs) as the core material. These particles serve as drug carriers delivering medications to the sites of bacterial infection. The casein (CAS) coated CCMPs disintegrate in the acidic environment produced by bacteria, facilitating precise drug release at the infection site. Unused particles can be safely eliminated from the mouth by rinsing or degrading into non-toxic compounds in the stomach’s acidic environment. In vitro experiments with encapsulated drugs of interest, including chlorhexidine (CHX), and doxycycline (DXC) within CCMPs, have demonstrated substantially enhanced drug release under acidic conditions. Considering the measured loading values, we estimate that 60 mg of CHX-loaded CCMPs in 1 mL media would supply 1.56 mg/mL of CHX, which is the same CHX concentration found in commercially available Peridex mouthwash. This suggests that our product could match the therapeutic outcome of current treatments, while also offering the advantage of releasing the drug only at the infection site. Currently we are exploring enzyme-triggered drug release from CCMP-Drug-CAS that would pave the way for targeting inflamed dental tissues overexpressing various Matrix Metalloproteinases such as MMP-9. Incorporating these CCMPs based on non-toxic calcium carbonate cores into dentifrices has the potential to reduce oral drug doses, addressing concerns of drug overexposure while expanding at-home oral care options.