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3D-printed dual drug delivery nanoparticle- loaded hydrogels to combat antibiotic-resistant bacteria.

ABSTRACT: 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.

SUBMITTER: Martinez-Perez D

PROVIDER: S-EPMC10236340 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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3D-printed dual drug delivery nanoparticle- loaded hydrogels to combat antibiotic-resistant bacteria.

Martínez-Pérez David D Guarch-Pérez Clara C Purbayanto Muhammad Abiyyu Kenichi MAK Choińska Emilia E Riool Martijn M Zaat Sebastian A J SAJ Wojciech Święszkowski Ś

International journal of bioprinting 20230213 3

Implant-associated infections are not easy to diagnose and very difficult to treat, due to the ability of major pathogens, such as <i>Staphylococcus aureus,</i> 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 m ...[more]

PMID: 37273978

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Project description:Hydrogels allow for controlling the diffusion rate and amount of solute according to the hydrogel network and thus have found many applications in drug delivery, biomaterials, toxicology, and tissue engineering. This paper describes a 3D-printed microfluidic chip for the straightforward partitioning of hydrogel barriers between microchannels. We use a previously-reported 3-channel architecture whereby the middle channel is filled with a hydrogel - acting like a porous barrier for diffusive transport - and the two side channels act as sink and source; the middle channel communicates with the side channels via orthogonal, small capillary channels that are also responsible for partitioning the hydrogel during filling. Our 3D-printed microfluidic chip is simple to fabricate by stereolithography (SL), inexpensive, reproducible, and convenient, so it is more adequate for transport studies than a microchip fabricated by photolithographic procedures. The chip was fabricated in a resin made of poly(ethylene glycol) diacrylate (PEG-DA) (MW = 258) (PEG-DA-258). The SL process allowed us to print high aspect ratio (37 : 1) capillary channels (27 μm-width and 1 mm-height) and enable the trapping of liquid-phase hydrogels in the hydrogel barrier middle channel. We studied the permeability of hydrogel barriers made of PEG-DA (MW = 700) (PEG-DA-700, 10% polymer content by wt. in water) - as a model of photopolymerizable barriers - and agarose (MW = 120 000, 2% polymer content by wt. in water) - as a model of thermally-gelled barriers. We measured the diffusion of fluorescein, 10k-dextran-Alexa 680 and BSA-Texas Red through these barriers. Fluorescein diffusion was observed through both 10% PEG-DA-700 and 2% agarose barriers while 10k-dextran-Alexa 680 and BSA-Texas Red diffused appreciably only through the 2% agarose hydrogel barrier. Our microfluidic chip facilitates the tuning of such barriers simply by altering the hydrogel materials. The straightforward trapping of selective barriers in 3D-printed microchannels should find wide applicability in drug delivery, tissue engineering, cell separation, and organ-on-a-chip platforms.

Dataset Information

3D-printed dual drug delivery nanoparticle- loaded hydrogels to combat antibiotic-resistant bacteria.

Publications

3D-printed dual drug delivery nanoparticle- loaded hydrogels to combat antibiotic-resistant bacteria.

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