Design of an Antibacterial/Analgesic Drug Delivery System for Oral Applications

Objectives: To synthesize and characterize a drug delivery system (DDS) with antimicrobial and analgesic properties for oral application.
Methods: The interaction index (II) of a chlorhexidine(CHX) - dexketoprofen(DEX) combination was determined by the formalin model in Wistar rats. PLGA-CHX microspheres (MS-CHX) were prepared by double emulsion method, dissolving PLGA(50:50) and adding 2%CHX plus 2%PVA. The combination was homogenized with ultrasonication, and the drying process was performed for 24 hours. The MS-CHX were characterized by SEM, EDS, DSC, TGA and FT-IR; and its antimicrobial effect was evaluated by Kirby-Bauer diffusion test on ATCC® strains (29212, 90028, 8739 and 25923), using 20µL of dissolved MS-CHX. A PEG hydrogel loaded with DEX (HG-DEX) was synthetized using a PEG combination (400/4000 mw) containing 2,5% DEX. The preparation process was performed at 97°C. Analgesic hydrogel was characterized by microscopy, DSC and TGA; and its cytotoxic effect was evaluated by MTS method with human osteoblasts culture. A HG-DEX + MS-CHX DDS was prepared and characterized. The release profile of both drugs was determined by HPLC. All statistical tests were determined with 95% of confidence, the data normality was assessed by Shapiro-Wilks test, and the between-groups differences were evaluated by ANOVA planned contrast.
Results: The CHX/DEX combination showed pharmacological synergism (II=0.3112, p<0.05) determined by Tallarida method. The MS-CHX showed homogeneous spherical/porous surface and antimicrobial effect when compared with blank MS (p<0.05). No alteration of the CHX antimicrobial effect during the preparation process was confirmed. The HG-DEX showed acceptable homogeneity, and didn’t showed to be cytotoxic when compared with control group (p<0.05). The drug release profile was quantified, and could be adjusted for optimal concentrations by customizing the HG:MS proportions.
Conclusions: The MS-CHX/HG-DEX DDS showed optimal physical and chemical characteristics; with promising antimicrobial and analgesic properties to be use in different oral lesions or surgical interventions.