TY - JOUR
T1 - 3D-printed dual drug delivery nanoparticle- loaded hydrogels to combat antibiotic-resistant bacteria
AU - Martínez-Pérez, David
AU - Guarch-Pérez, Clara
AU - Purbayanto, Muhammad Abiyyu Kenichi
AU - Choińska, Emilia
AU - Riool, Martijn
AU - Zaat, Sebastian A J
AU - Wojciech, Święszkowski
N1 - Copyright: © 2023 Martínez-Pérez D, Guarch-Pérez C, Purbayanto MAK, et al.
PY - 2023
Y1 - 2023
N2 - Implant-associated infections are not easy to diagnose and very difficult to treat, due to the ability of major pathogens, such as Staphylococcus aureus, to develop biofilms and escape the immune response and antibiotic treatment. We, therefore, aimed to develop a 3D-printed dual rifampicin (Rif)- and vancomycin (Van)-loaded polylactic- co-glycolic acid (PLGA) nanoparticles (NPs) delivery system based on hydrogels made of gelatin methacrylate (GelMA). The release of Rif and Van from NPs manufactured from different PLGA molecular weights was studied in phosphate-buffered saline for 21 days. Low molecular weight PLGA NPs exhibited the fastest release of Rif and Van within the first 7 days and were selected for antimicrobial evaluation. Four different GelMA-based 3D-printed samples were successfully produced, carrying non-loaded NPs, Rif-NPs, Van-NPs, or alternating layers of Rif-NPs and Van-NP. The exposition of S. aureus against increased concentrations of Rif or Van produced new resistant strains to Rif (Rif R) or Van (Van R). The GelMA hydrogel co-delivering Rif and Van eradicated S. aureus RN4220 Rif R and RN4220 Van R strains. S. aureus RN4220 and S. aureus AMC 201 colonies developed resistance to Rif after contact with the GelMA hydrogel containing only Rif-NPs which appeared to be due to known mutations in the rpoB gene. In conclusion, 3D-printed GelMA hydrogel loaded with PLGA Rif-Van-NPs drug delivery system show promising in vitro results to prevent implant-associated infections caused by antimicrobial-resistant bacteria.
AB - Implant-associated infections are not easy to diagnose and very difficult to treat, due to the ability of major pathogens, such as Staphylococcus aureus, to develop biofilms and escape the immune response and antibiotic treatment. We, therefore, aimed to develop a 3D-printed dual rifampicin (Rif)- and vancomycin (Van)-loaded polylactic- co-glycolic acid (PLGA) nanoparticles (NPs) delivery system based on hydrogels made of gelatin methacrylate (GelMA). The release of Rif and Van from NPs manufactured from different PLGA molecular weights was studied in phosphate-buffered saline for 21 days. Low molecular weight PLGA NPs exhibited the fastest release of Rif and Van within the first 7 days and were selected for antimicrobial evaluation. Four different GelMA-based 3D-printed samples were successfully produced, carrying non-loaded NPs, Rif-NPs, Van-NPs, or alternating layers of Rif-NPs and Van-NP. The exposition of S. aureus against increased concentrations of Rif or Van produced new resistant strains to Rif (Rif R) or Van (Van R). The GelMA hydrogel co-delivering Rif and Van eradicated S. aureus RN4220 Rif R and RN4220 Van R strains. S. aureus RN4220 and S. aureus AMC 201 colonies developed resistance to Rif after contact with the GelMA hydrogel containing only Rif-NPs which appeared to be due to known mutations in the rpoB gene. In conclusion, 3D-printed GelMA hydrogel loaded with PLGA Rif-Van-NPs drug delivery system show promising in vitro results to prevent implant-associated infections caused by antimicrobial-resistant bacteria.
U2 - 10.18063/ijb.683
DO - 10.18063/ijb.683
M3 - Article
C2 - 37273978
SN - 2424-8002
VL - 9
SP - 683
JO - International Journal of Bioprinting
JF - International Journal of Bioprinting
IS - 3
ER -