In-situ forming implants for dual controlled release of chlorhexidine and ibuprofen for periodontitis treatment: Microbiological and mechanical key properties

Abstract

In-situ forming implants (ISFI) which simultaneously release an antimicrobial and anti-inflammatory drug in a controlled manner offer an interesting potential for local periodontitis treatment. In this study, poly(lactic-co-glycolic acid) (PLGA)-based implants loaded with chlorhexidine and ibuprofen were investigated, in particular with respect to their antimicrobial and mechanical key properties. PLGA (Resomer RG 502H) was dissolved in N-methyl pyrrolidone (NMP). Chlorhexidine dihydrochloride and ibuprofen (free acid) were added as well as acetyltributyl citrate (ATBC) as plasticizer and hydroxypropyl methylcellulose (HPMC, Methocel, E50) as adhesion enhancer. Upon contact with aqueous fluids, the NMP diffuses out and water into the formulation, causing polymer precipitation and drug entrapment. The antimicrobial activity against periodontal pathogens was studied using the agar-well diffusion test, time-kill studies and growth curve method. The syringeability of the liquid formulations and mechanical key properties of the in-situ formed implants were investigated using a texture analyzer. A commercially available gel used for local periodontitis treatment, loaded with chlorhexidine dihydrochloride and chlorhexidine digluconate (Chlo-site) was studied for reasons of comparison. Importantly, the investigated ISFIs showed a strong and rapid antibacterial activity against all the selected pathogens, while maintaining suitable mechanical properties. The simultaneous release of ibuprofen did not reduce the desired antimicrobial effect of chlorhexidine.