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Prosthetic joint infections (PJIs) ensued from total joint replacement (TJR) pose a severe threat to patients that involve poor health outcomes, severe pain, death (in severe cases), and negative influence patients’ quality of life. Antibiotic-loaded bone cement (ALBC) is frequently used for the prevention and treatment of PJI. This work aims to study gentamicin release from carbon nanotubes (CNTs) incorporated in polymethyl methacrylate (PMMA) bone cement to prolong release over several weeks to provide prophylaxis from PJIs after surgery. Different CNT concentrations were tested with the presence of gentamicin as a powder or preloaded onto carboxyl functionalized CNTs. The different types of bone cement were tested for drug release, mechanical properties, water uptake, antimicrobial properties, and cytocompatibility with human osteoblast cells (MTT, LDH, alizarin red, and morphology). Results showed prolonged release of gentamicin from CNT-loaded bone cements over several weeks compared to gentamicin-containing bone cement. Additionally, the presence of CNT enhanced the percentage of gentamicin released without adversely affecting the nanocomposite mechanical and antimicrobial properties needed for performance. Cytotoxicity testing showed non-inferior performance of the CNT-containing bone cement to the equivalent powder containing cement. Therefore, the developed nanocomposites may serve as a novel PMMA bone cement to prevent PJIs.

Prosthetic joint infections (PJIs) ensued from total joint replacement (TJR) pose a severe threat to patients that involve poor health outcomes, severe pain, death (in severe cases), and negative influence patients' quality of life. Antibiotic-loaded bone cement (ALBC) is frequently used for the prevention and treatment of PJI. This work aims to study gentamicin release from carbon nanotubes (CNTs) incorporated in polymethyl methacrylate (PMMA) bone cement to prolong release over several weeks to provide prophylaxis from PJIs after surgery. Different CNT concentrations were tested with the presence of gentamicin as a powder or preloaded onto carboxyl functionalized CNTs. The different types of bone cement were tested for drug release, mechanical properties, water uptake, antimicrobial properties, and cytocompatibility with human osteoblast cells (MTT, LDH, alizarin red, and morphology). Results showed prolonged release of gentamicin from CNT-loaded bone cements over several weeks compared to gentamicin-containing bone cement. Additionally, the presence of CNT enhanced the percentage of gentamicin released without adversely affecting the nanocomposite mechanical and antimicrobial properties needed for performance. Cytotoxicity testing showed non-inferior performance of the CNT-containing bone cement to the equivalent powder containing cement. Therefore, the developed nanocomposites may serve as a novel PMMA bone cement to prevent PJIs. [ABSTRACT FROM AUTHOR]

Introduction: Antibiotic-loaded poly(methyl methacrylate) bone cements (ALBCs) are widely used in total joint replacement (TJR), for local delivery of antibiotics to provide prophylaxis against prosthetic joint infections (PJI). One of the shortcomings of the current generation of ALBCs is that the antibiotic release profile is characterized by a burst over the first few hours followed by a sharp decrease in rate for the following several days (often below minimum inhibitory concentration (MIC)), and, finally, exhaustion (after, typically, ~ 20 d). This profile means that the ALBCs provide only short-term antimicrobial action against bacterial strains involved PJI. Rationale: The purpose of the present study was to develop an improved antibiotic delivery system for an ALBC. This system involved using a layer-by-layer technique to load the antibiotic (gentamicin sulphate) (GEN) on silica nanoparticles, which are then blended with the powder of the cement. Then, the powder was mixed with the liquid of the cement (NP-GEN cement). For controls, two GEN-loaded brands were used (Cemex Genta and Palacos R+G). Gentamicin release and a host of other relevant properties were determined for all the cements studied. Results: Compared to control cement specimens, improved GEN release, longer antimicrobial activity (against clinically-relevant bacterial strains), and comparable setting time, cytocompatibility, compressive strength (both prior to and after aging in PBS at 37 oC for 30 d), 4-point bend strength and modulus, fracture toughness, and PBS uptake. Conclusions: NP-GEN cement may have a role in preventing or treating PJI. [ABSTRACT FROM AUTHOR]

Layer-by-layer (LbL) deposition is a versatile technique that has been employed in numerous industrial applications i.e. biomaterials, drug delivery and electronics to confer peculiar properties to the system. When LbL is employed for drug delivery, the active molecule is sandwiched between layers of polyelectrolytes and the release is controlled by the diffusion of the drug through the layers and the possible hydrolysis of the coating (delamination). Poly-beta-amino-esters (PBAEs) are a class of hydrolysable polyelectrolytes that have been widely used in DNA delivery and for LbL on medical devices. Their use allowed the controlled release of antibiotics and other bioactive compounds from the surface of medical devices without cytotoxic effects. The general accepted consensus is that drug released from LbL coating assembled using PBAEs is the results of the polymer hydrolysis; however, no attention has been paid to the role of the electrostatic attraction between PBAE and the other polyelectrolyte utilised in the LbL assembly. In this work, we prepared LbL coatings on the surface of silica nanoparticles entrapping gentamicin as model drug and demonstrated that the drug release from PBAEs containing LbL coatings is predominantly controlled by the electrostatic attraction between opposite charged electrolytes. The positive charge of PBAE decreased from pH = 5 to pH = 7.4 while alginate negative charges remained unchanged in this pH range while PBAE hydrolysis kinetics was faster, as determined with Gel Permeation Chromatography (GPC), in acidic conditions. When PBAE were employed in the LbL construct higher levels of drug were released at pH = 7.4 than at pH = 5; additionally, replacing PBAE with chitosan (the charge of chitosan is not influenced in this pH range) resulted in comparable gentamicin release kinetics at pH = 5. [ABSTRACT FROM AUTHOR]

• Silica nanoparticles were loaded with gentamicin through various routes: Layer-by-layer (LbL), entrapment and adsorption. • LbL achieved better loading and control for release compared to the entrapment and adsorption methods. • Polyelectrolytes protonation increases charge accumulation and repulsion, leading to LbL coat swelling with enhanced drug permeability and release. • Deprotonation of ionizable groups causes decreased polymer interaction and LbL shrinkage, leading to lowered permeability and drug release. Controlling antibiotic release kinetics is essential for effective treatment and for many biomedical applications. Herein, silica nanoparticles were prepared and loaded with gentamicin through various routes (Layer-by-layer (LbL), entrapment, adsorption). LbL coatings involved the polyelectrolytes poly(styrene sulfonate) (PSS) and Poly(allylamine hydrochloride) (PAH), where the nanoparticles coated with quadruple layers (QL) of [PSS/gentamicin/PSS/PAH]. The nanoparticles were characterized by zeta potential, transmission electron microscope (TEM) and thermogravimetric analysis (TGA). Moreover, nanoparticles' gentamicin release was tested in different release media (acetate buffer pH 5 and PBS pH 7.4). The gentamicin LbL-coated nanoparticles were successful to sustain drug release over 2 weeks. Although the entrapment method was similarly able to sustain drug release over two weeks, it showed lower drug loading when compared to the LbL-coated nanoparticles. In contrast, simple adsorption on bare silica surface resulted in significantly lower drug loading and 90 % release on day 1. The release of gentamicin showed pH-responsive behavior, with higher release at pH 5. This work demonstrates that gentamicin release from silica nanocarriers can be controlled by the different approaches for loading gentamicin. This will give different release profiles tailored for many biomedical applications such as antibiotic-loaded bone cement or implant coatings. [ABSTRACT FROM AUTHOR]