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article · International Journal of Pharmaceutics X

Functionalized surface of PLGA nanoparticles in thermosensitive gel to enhance the efficacy of antibiotics against antibiotic resistant infections in endodontics: A randomized clinical trial

202318 citationsOpen accessBritish University in Egypt

In plain language

Root canal infections linked to Enterococcus faecalis frequently resist standard therapies due to stubborn bacterial biofilms forming on dentin. To overcome this, researchers evaluated a thermosensitive hydrogel loaded with ciprofloxacin hydrochloride encapsulated within chitosan-coated PLGA nanoparticles. When tested as an endodontic medication, the formulation gels near body temperature and delivers sustained antibiotic release. In clinical evaluations on patients, this nanoparticle-gel system was compared to a free-antibiotic gel alongside traditional ciprofloxacin and calcium hydroxide pastes. The nanoparticle hydrogel demonstrated the highest rates of biofilm inhibition and bacterial reduction. By exploiting small particle size and surface positive charges to target bacterial cells, the nanocarrier system delivered the drug deep into the root canal, sustaining its therapeutic activity to effectively counter recurrent infections.

Key takeaways

  • Ciprofloxacin-loaded PLGA nanoparticles coated with chitosan were successfully incorporated into a Pluronic-based thermosensitive hydrogel.
  • The formulation demonstrated a gelation temperature close to human body temperature, high viscosity, and a sustained drug release of roughly fifty percent after 72 hours.
  • A randomised clinical trial demonstrated that the nanoparticle gel achieved the highest total bacterial reduction and biofilm inhibition against recurrent Enterococcus faecalis infections compared to standard treatments.

Why it matters

Persistent root canal infections are difficult to cure because bacteria form protective biofilms that withstand traditional disinfection pastes. By deploying temperature-responsive gels carrying antibiotic-loaded nanoparticles, clinicians can ensure medications reach deep into infected dental structures and remain active over extended periods. This approach offers a targeted strategy to eradicate difficult bacterial strains and reduce treatment failures in dental care.

Commercialisation angle

This technology represents an applied and clinically tested endodontic treatment. It is aimed at dental practitioners, endodontists, and manufacturers of specialised root canal therapeutics. Because the material has already demonstrated efficacy in human patient trials against standard pastes, it occupies an advanced stage of development. Moving towards market adoption would depend on formal regulatory approvals, scale-up of the nano-formulation, and broader clinical validation.

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Abstract

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.

Research topics

  • Endodontics and Root Canal Treatments
  • Oral microbiology and periodontitis research
  • Dental Anxiety and Anesthesia Techniques

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DOI: 10.1016/j.ijpx.2023.100219

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