Design and characterization of digluconate and diacetate chlorhexidine loaded-PLGA microparticles for dental applications

Abstract

Chlorhexidine solutions are widely used in dentistry, from caries prevention to endodontic disinfection. This biguadine presents a broad spectrum and can be bacteriostatic/bactericide depending on the concentration and time-lapse used. Chlorhexidine diacetate (CDA) and digluconate (CDG) are the most common salts used in dental practice. While CDA saturation occurs at 2%, CDG presents higher solubity and is therefore used as diluted solutions or gels. CDG is the antiseptic of choice for oral rinses because it is less likely to irritate mucous membranes. Although it is very efficient in bacterial control, it presents some drawbacks such as teeth and/or restoration staining, taste alterations and tongue discoloration. Therefore, technological improvement is very desirable to promote its sustained release and avoid those issues. This study aimed to develop and characterize microparticles of chlorhexidine loaded poly (D,L-lactide-co-glycolide) (PLGA) for dental applications. CDA and CDG microparticles were prepared by spray-drying technique and characterized in terms of particle size, polydispersity (pdI), morphology, stability, yield of production, encapsulation efficacy (EE), drug loading (DL), cumulative release and antibacterial response. The yield of production showed the best result for CDA (over 71.56%). Morphological appreciation showed homogenous, spherical and non-aggregated microparticles. Particle size ranged from 1.01 to 3.07 μm, while pdI remained below 0.3. The microencapsulation process resulted in EE in the range of 7.05–34.72% and DL between 0.41 and 4.08%. The microencapsulation resulted in a controlled release pattern for both salts. CDA microparticles presented a more sustained pattern, while CDG presented a more pronounced burst effect. Finally, CDA and CDG content of the microparticles were able to inhibit Streptococcus mutans in vitro. Accordingly, the PLGA-based microparticles represent a suitable alternative for oral health applications where CDA and CDG in the solid-state and a controlled release pattern of chlorhexidine up to 120 days is strategic, such as in the composition of new dental materials with anti-caries properties.