Polycarbophil Calcium

Treating oral diseases remains challenging as API is quickly washed out of the application site by saliva turnover and mouth movements. In situ gels are a class of application forms that present sol-gel transition's ability as a response to stimuli. Their tunable properties are provided using smart polymers responsible for stimuli sensitivity, often providing mucoadhesivity. In this study, antimicrobial in situ gels of thermosensitive and pH-sensitive polymers loaded with silver nanoparticles were prepared and evaluated. The nanoparticles were prepared by green synthesis using Agrimonia eupatoria L. extract. According to the data analysis, the in situ gel with the most promising profile contained 15 % of Pluronic® F-127, 0.25 % of methylcellulose, and 0.1 % of Noveon® AA-1. Pluronic® F-127 and methylcellulose significantly increased the viscosity of in situ gels at 37 °C and shear rates similar to speaking and swallowing. At 20 °C, a behavior close to a Newtonian fluid was observed while being easily injectable (injection force 13.455 ± 1.973 N). The viscosity of the formulation increased with temperature and reached 2962.77 ± 63.37 mPa·s (37 °C). A temperature increase led to increased adhesiveness and rigidity of the formulation. The critical sol-gel transition temperature at physiological pH was 32.65 ± 0.35 °C. 96.77 ± 3.26 % of Ag NPs were released by erosion and dissolution of the gel after 40 min. The determination of MIC showed effect against E. coli and S. aureus (0.0625 mM and 0.5000 mM, respectively). The relative inhibition zone diameter of the in situ gel was 73.32 ± 11.06 % compared to gentamicin sulfate. This work discusses the optimization of the formulation of novel antibacterial in situ gel for oromucosal delivery, analyses the impact of the concentration of excipients on the dependent variables, and suggests appropriate evaluation of the formulation in terms of its indication. This study offers a promising dosage form for local treatment of oral diseases.

Periodontal diseases are a global oral health problem affecting almost 10% of the global population. Porphyromonas gingivalis is one of the main bacteria involved in the initiation and progression of inflammatory processes as a result of the action of the cysteine proteases lysin- and arginine-gingipain. Surelease/polycarbophil microparticles containing a lyophilized proanthocyanidin-enriched fraction from the rhizomes of Limonium brasiliense, traditionally named “baicuru” (ethyl acetate fraction), were manufactured. The ethyl acetate fraction was characterized by UHPLC by the presence of samarangenins A and B (12.10 ± 0.07 and 21.05 ± 0.44%, respectively) and epigallocatechin-3-O-gallate (13.44 ± 0.27%). Physiochemical aspects of Surelease/polycarbophil microparticles were characterized concerning particle size, zeta potential, entrapment efficiency, ethyl acetate fraction release, and mucoadhesion. Additionally, the presence of the ethyl acetate fraction-loaded microparticles was performed concerning potential influence on viability of human buccal KB cells, P. gingivalis adhesion to KB cells, gingipain activity, and P. gingivalis biofilm formation. In general, all Surelease/polycarbophil microparticles tested showed strong adhesion to porcine cheek mucosa (93.1 ± 4.2% in a 30-min test), associated with a prolonged release of the ethyl acetate fraction (up to 16.5 ± 0.8% in 24 h). Preincubation of KB cells with Surelease/polycarbophil microparticles (25 µg/mL) resulted in an up to 93 ± 2% reduced infection rate by P. gingivalis. Decreased activity of the P. gingivalis-specific virulence factors lysin- and arginine-gingipain proteases by Surelease/polycarbophil microparticles was confirmed. Surelease/polycarbophil microparticles decreased biofilm formation of P. gingivalis (97 ± 2% at 60 µg/mL). Results from this study prove the promising activity of Surelease/polycarbophil microparticles containing ethyl acetate fraction microparticles as a prophylaxis strategy to prevent the recurrence of P. gingivalis.