Journal Article

LbL-assembled gentamicin delivery system for PMMA bone cements to prolong antimicrobial activity

Yang, Lirong, Perni, Stefano, Prokopovich, Polina, Jones, Steve A, Al Thaher, Yazan

2018

Overview

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. 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. 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. NP-GEN cement may have a role in preventing or treating PJI.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aging / Aminoglycosides / Analysis / Anti-Infective Agents - administration & dosage / Anti-Infective Agents - pharmacokinetics / Anti-Infective Agents - toxicity / Antibiotics / Antiinfectives and antibacterials / Antimicrobial activity / Antimicrobial agents / Bend strength / Biocompatibility / Biofilms / Biology and Life Sciences / Biomedical materials / Bone cements / Bone Cements - chemistry / Bone Cements - toxicity / Cell cycle / Cell Line / Cell Survival - drug effects / Cement / Compressive Strength / Dosage and administration / Drug Delivery Systems / Drugs / Engineering and Technology / Exhaustion / Fracture toughness / Fractures / Gene expression / Gentamicin / Gentamicins / Gentamicins - administration & dosage / Gentamicins - pharmacokinetics / Gentamicins - toxicity / Humans / Implants, Artificial / Infection / Infections / Joint replacement / Joint surgery / Knee / Materials Testing / Mechanical properties / Medicine and Health Sciences / Methyl methacrylate / Microbial Sensitivity Tests / Minimum inhibitory concentration / Nanoparticles / Nanoparticles - chemistry / Nanostructured materials / Nanotechnology / Osteoblasts - cytology / Osteoblasts - drug effects / Osteoblasts - metabolism / Pharmaceutical sciences / Pharmacy / Physical Sciences / Polymerization / Polymethyl methacrylate / Polymethyl Methacrylate - chemistry / Polymethyl Methacrylate - toxicity / Polymethylmethacrylate / Powder / Powders (Particulate matter) / Prevention / Prophylaxis / Prostheses / Prostheses and implants / Prosthesis / Prosthesis-Related Infections - prevention & control / Research and Analysis Methods / Rheology / Risk factors / Silica / Silicon Dioxide / Sodium / Strains (organisms) / Surgery / Surgical wound infections / Time compression / Vehicles