(303k) Periodontal Biofilm Eradication By Doxycycline Loaded Magnetic Microfibers.

Periodontitis is a chronic inflammation of the soft tissue surrounding the teeth that leads to the formation of multi-species bacterial biofilms. The disease affects a large portion of the global population and is associated with an increased risk of stroke, hypertension and inflammatory bowel disease. Current treatment of periodontitis is challenging due to the high antibiotic resistance of biofilms, and the difficulty to sustain a sufficient antimicrobial concentration in the oral cavity. Therefore, there is a need to identify novel treatment strategies capable of eradicating established biofilms. Magnetic hyperthermia induced by superparamagnetic iron oxide nanoparticles (SPIONs) has been demonstrated to be effective against bacterial infection.¹ The thermogenic bactericidal approach can facilitate an increased uptake of antibiotics to the bacterial cells and also overcome the limitations of chemical biocides. This study presents a potential local treatment of periodontitis using microfiber composite, which induces local magnetic hyperthermia and antibiotic release for a synergistic biofilm treatment.

Manganese ferrite nanoparticles (Mn_0.5Fe_2.5O₄) of size 18 nm were synthesized using flame spray pyrolysis (FSP). These doped SPIONs show greater magnetic hyperthermia compared to undoped SPIONs.² Thus, Mn_0.5Fe_2.5O₄ nanoparticles were incorporated into poly(methyl methacrylate) (PMMA) microfibers by electrospinning. Electrospun microfibers were also prepared using poly(lactic-co-glycolic acid) (PLGA) and loaded with doxycycline hyclate (DXY). The PMMA/SPION and PLGA/DXY microfibers were combined into a composite structure and evaluated for their effect on periodontal biofilms.

PMMA/SPION microfibers reached a temperature of 42-43 °C upon exposure to an alternating magnetic field (AMF), at clinically relevant AMF amplitude and frequency. The PLGA/DXY microfiber showed a cumulative release of 35.3% of the loaded drug in the first 5 min of the in vitro drug release study and plateaued at an accumulated dose of 47 μgmL^−1 after 24 h. The two microfiber materials were successfully joined by compacting them at 65 °C.

Electrospinning was successfully used to produce PMMA/SPION and PLGA/DXY microfibers. The magnetic and drug loaded microfibers show mild hyperthermia and sufficient drug release, respectively. This study demonstrates that DXY loaded magnetic microfibers can be used to eradicate periodontal biofilms.

Acknowledgement:

The authors would like to acknowledge the financial support from the Science for Life Laboratory. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 101002582).

References:

(1) Alumutairi, L.; Yu, B.; Filka, M.; Nayfach, J.; Kim, M.-H. Mild Magnetic Nanoparticle Hyperthermia Enhances the Susceptibility of Staphylococcus Aureus Biofilm to Antibiotics. Int. J. Hyperth., 2020, 37 (1), 66–75.

(2) Ansari, S. R.; Hempel, N. J.; Asad, S.; Svedlindh, P.; Bergström, C. A. S.; Löbmann, K.; Teleki, A. Hyperthermia-Induced in Situ Drug Amorphization by Superparamagnetic Nanoparticles in Oral Dosage Forms. ACS Appl. Mater. Interfaces, 2022, 14 (19), 21978–21988.