TY - JOUR
T1 - 3D-printed dual drug delivery nanoparticleloaded 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 - Święszkowski, Wojciech
N1 - Funding Information: This work was funded by the research project PRINT-AID within the EU Framework Programme for Research and Innovation Horizon 2020 – Marie Skłodowska-Curie Innovative Training Networks under grant agreement No. 722467 and by the National Centre for Research and Development under the grant no. Funding Information: This work was funded by the research project PRINTAID within the EU Framework Programme for Research and Innovation Horizon 2020 – Marie Skłodowska-Curie Innovative Training Networks under grant agreement No. 722467 and by the National Centre for Research and Development under the grant no. TECHMATSTRATEG2/407770/2/NCBR/2020 entitled New functional MATerials for 3D printing in UROlogy needs, acronym MATURO 3D Publisher Copyright: © 2023 Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution License, permitting distribution, and reproduction in any medium, provided the original work is properly cited
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 polylacticco-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 (RifR) or Van (VanR). The GelMA hydrogel co-delivering Rif and Van eradicated S. aureus RN4220 RifR and RN4220 VanR 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.
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 polylacticco-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 (RifR) or Van (VanR). The GelMA hydrogel co-delivering Rif and Van eradicated S. aureus RN4220 RifR and RN4220 VanR 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.
KW - 3D printing
KW - Antibiotic resistance
KW - Controlled drug delivery
KW - Gelatin methacrylate
KW - Nanoparticles
KW - Staphylococcus aureus
UR - http://www.scopus.com/inward/record.url?scp=85150858583&partnerID=8YFLogxK
U2 - https://doi.org/10.18063/IJB.683
DO - https://doi.org/10.18063/IJB.683
M3 - Article
SN - 2424-8002
VL - 9
SP - 64
EP - 79
JO - International Journal of Bioprinting
JF - International Journal of Bioprinting
IS - 3
ER -