Mechanistic analysis of PLGA/HPMC-based in-situ forming implants for periodontitis treatment

Abstract

In-situ forming implant formulations based on poly(lactic-co-glycolic acid) (PLGA), acetyltributyl citrate (ATBC), minocycline HCl, N-methyl pyrrolidone (NMP) and optionally hydroxypropyl methylcellulose (HPMC) were prepared and thoroughly characterized in vitro. This includes electron paramagnetic resonance (EPR), nuclear magnetic resonance (1H NMR), mass change and drug release measurements under different conditions, optical microscopy, size exclusion chromatography (SEC) as well as antibacterial activity tests using gingival crevicular fluid samples from periodontal pockets of periodontitis patients. Based on these results, deeper insight into the physico-chemical phenomena involved in implant formation and the control of drug release could be gained. For instance, the effects of adding HPMC to the formulations, resulting in improved implant adherence and reduced swelling, could be explained. Importantly, the in-situ formed implants effectively hindered the growth of bacteria present in the patients’ periodontal pockets. Interestingly, the systems were more effectively hindering the growth of pathogenic bacterial strains (e.g., Fusobacterium nucleatum) than that of strains with a lower pathogenic potential (e.g., Streptococcus salivarius). In vivo, such a preferential action against the pathogenic bacteria can be expected to give a chance to the healthy flora to re-colonize the periodontal pockets.