# Antimicrobials in Dentistry
## 2 Antimicrobials Used in Dentistry
### Chlorlexidine  
Chlorlexidine (CHX) is a cationic compound with broad-spectrum antibacterial activity (Figure 1). It causes disruption of cellular membranes and has been used successfully as an antimicrobial agent in dentistry for the management of oral biofilms [20, 21, 22]. It is a key component in oral formulations such as mouthwashes and oral gels that can be used topically in the management of oral biofilms. Combining CHX in polymeric matrices have been attempted for sustained delivery specifically in polyalkenoate cements, commonly known as glass ionomer cements (GIC) that contain water soluble polymers such as poly (acrylic acid), poly (maleic) and poly(titaconic acid), which undergo an acid-base reaction to yield a cement. Although incorporation of CHX in GIC enables better protection against caries, it results in cements with inferior mechanical properties that exhibit a less than optimal period of sustained release [22,23]. Other derivatives of CHX such as CHXacetate and chloride have also been incorporated in GICs; however, using CHX diacetate exhibits release over a few days, whilst a very rapid release occurs with CHX chloride. [PERSON] et al. [24] reported a CHX hexametaphosphate salt that exhibited lower solubility, and laboratory studies showed that incorporation and release from GICs could be sustained over 48 months [23], this being dependent on dose. This compound was also explored for release from elastomeric ligatures [25] used in orthodontic treatments, and the experimental results showed that functionalisation of these elastomeric polymers with CHX hexametaphosphate under controlled conditions did not have detrimental effects on the mechanical properties; however, further work will be required to ascertain its appropriate function. Although there is clear evidence that CHX is effective for the control of specific conditions such as controlling plaque and gingivitis [26,27], it is important to consider antimicrobial resistance and adverse reactions when designing drug delivery systems despite the fact that controlled release from polymeric systems is potentially more efficacious, especially for targeted release.  
Apart from its antimicrobial activity, CHX has been shown to inhibit the activity of matrix metalloproteinases (MMPs) 2, 8 and 9 as well as cysteine cathepsins (CPs) [28,29]. At concentrations as low as 0.2%, CHX has been reported to preserve the collagen matrix in hybrid layers and reduce the degradation of resin-dentine bonds [30,31]. Since MMPs depend on calcium to maintain their tertiary structure and zinc to perform their catalytic activity [32,33], it is hypothesized that CHX acts by inhibiting the binding of calcium and zinc ions to the MMPs, thereby reducing their catalytic activity [34]. Since establishing the role of CHX as an efficient enzyme inhibitor, several efforts have been made to incorporate  
Figure 1: Chemical structure of chlorhexidine (CHX), a cationic compound with broad-spectrum antibacterial activity.  
it into the components of dental adhesive systems [35; 36]. However, since the binding of the cationic CHX to the anionic sites in mineralised and demineralised dentine (phosphate group in hydroxyapatite and carboxyl group in collagen) is electrostatic, this is found to be reversible within 18 months [37; 38]. Deterioration is further accelerated when \"wet bonding\" is performed with etch-and-rines adhesives or hydrophilic self-etch adhesives, as CHX may leach out due to the hydrolytic medium created by the incompletely removed water [39].