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Functionalized surface of PLGA nanoparticles in thermosensitive gel to enhance the efficacy of antibiotics against antibiotic resistant infections in endodontics: A randomized clinical trial.
International journal of pharmaceutics: X. 2023 December 16
Enterococcus faecalis plays the key role in endodontic infections and is responsible for the formation of biofilm on dentin, which causes a resistance against periradicular lesions treatment, consequently the aim of this study is to use nanoparticles entrapping anibacterial agents coated with chitosan that in authors previous study showed a successful in vitro biofilm inhibition, additionally incorporated in thermoresponsive gel.to benefit nanoparticles` small size, and the positive charge of their surfaces that binds with the negatively charged surface of bacterial cell causing its destruction, in addition to the sustained release pattern of the drug based nanoparticles in gel. Therefore, Ciprofloxacin hydrochloride (CIP) encapsulated in PLGA nanoparticles coated with chitosan (CIP-CS-PLGA-NPs), in addition to free CIP, were incorporated in Pluronic® 407/188 to form thermosensitive gels (F1) and (F2), respectively. The thermosensitive gels were tested with regards to rheology, gelling temperature and the release pattern of the drug. A clinical study of the efficacy of F1 and F2 as antibacterial treatments was conducted on patients followed by a comparative studies against CIP and Ca(OH)2 pastes in terms of biofilm inhibition assay and total bacterial reduction count and percent.The results revealed that F1 and F2 exhibited gelation temperature of 36.9 ± 0.3 °C and 36.0 ± 0.4 °C, viscosity was 15,000 ± 360.6 and 7023.3 ± 296.8 cP respectively. The cumulative release of F1 and F2 after 72 h was 50.03% ± 0.7345 and 77.98% ± 3.122 respectively. F1 was the most efficient treatment against recurrent E.faecalis infection in endodontics that was evident by the highest total bacterial reduction count and percent and biofilm inhibition percent that were recorded in the group treated with F1followed by the group treated with F2. Nanocarriers succeeded in carrying the drug deeply in the root canal and sustaining its effect to abolish the obstinate E. faecalis recurrent infection and its biofilm formation.
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