Multi-scale strategy to eradicate Pseudomonas aeruginosa on surfaces using solid lipid nanoparticles loaded with free fatty acids.

Infections are both frequent and costly in hospitals around the world, leading to longer hospital stays, overuse of antibiotics, and excessive costs to the healthcare system. Moreover, antibiotic resistant organisms, such as Pseudomonas aeruginosa are increasing in frequency, leading to 1.7 million infections per year in USA hospitals, and 99,000 deaths, both due to the evolution of antibiotic resistance and the formation of biofilms on medical devices. In particular, respiratory infections are costly, deadly to 4.5 million persons per year worldwide, and can spread to the lungs through the placement of endotracheal tubing. In this study, towards a reduction in infections, solid lipid nanoparticles were formulated from free fatty acids, or natural lipophilic constituents found in tissues of the body. A strategy was developed to target infections by producing coatings made of non-toxic chemistries lauric acid and oleic acid delivered by core-shell solid lipid nanoparticles that act against bacteria by multiple mechanisms at the nanoscale, including disruption of bacteria leading to DNA release, and reducing the adhesion of dead bacteria to ~1%. This is the first such study to explore an anti-infection surface relying on these multi-tier strategies at the nanoscale.

Enhanced efficacy of superparamagnetic iron oxide nanoparticles against antibiotic-resistant biofilms in the presence of metabolites.

Antibiotic resistance and the lack of new antibacterial agents cause major challenges for the treatment of infections. Here, we describe a simple, broad-spectrum, and low-cost dual-sided approach which uses superparamagnetic iron oxide particles (SPION) in combination with fructose metabolites as an alternative to existing antibacterial strategies. This strategy offers further improved efficacy of SPION against persistent gram-positive and gram-negative bacteria infections by manipulating the biofilm metabolic microenvironment and outperforms vancomycin (the antibiotic of last resort), creating a new nanotechnology-driven approach.

Decreased cervical cancer cell adhesion on nanotubular titanium for the treatment of cervical cancer.

Cervical cancer can be treated by surgical resection, chemotherapy, and/or radiation. Titanium biomaterials have been suggested as a tool to help in the local delivery of chemotherapeutic agents and/or radiation to cervical cancer sites. However, current titanium medical devices used for treating cervical cancer do not by themselves possess any anticancer properties; such devices act as carriers for pharmaceutical agents or radiation sources and may even allow for the growth of cancer cells. Based on studies, which have demonstrated decreased lung, breast, and bone cancer cell functions on nanostructured compared to nanosmooth polymers, the objective of the present in vitro study was to modify titanium to possess nanotubular surface features and determine cervical cancer cell adhesion after 4 hours. Here, titanium was anodized to possess nanotubular surface features. Results demonstrated the ability to decrease cervical cancer cell adhesion by about a half on nanotubular compared to currently used nanosmooth titanium (without the use of chemotherapeutics or radiation), opening up numerous possibilities for the use of nanotubular titanium in local drug delivery or radiation treatment of cervical cancer.

Effects of different sterilization techniques and varying anodized TiO2 nanotube dimensions on bacteria growth.

Infection of titanium (Ti)-based orthopedic implants is a growing problem due to the ability of bacteria to develop a resistance to today's antibiotics. As an attempt to develop a new strategy to combat bacteria functions, Ti was anodized in the present study to possess different diameters of nanotubes. It is reported here for the first time that Ti anodized to possess 20 nm tubes then followed by heat treatment to remove fluorine deposited from the HF anodization electrolyte solution significantly reduced both S. aureus and S. epidermidis growth compared to unanodized Ti controls. It was further found that the sterilization method used for both anodized nanotubular Ti and conventional Ti played an important role in the degree of bacteria growth on these substrates. Overall, UV light and ethanol sterilized samples decreased bacteria growth, while autoclaving resulted in the highest amount of bacteria growth. In summary, this study indicated that through a simple and inexpensive process, Ti can be anodized to possess 20 nm tubes that no matter how sterilized (UV light, ethanol soaking, or autoclaving) reduces bacteria growth and, thus, shows great promise as an antibacterial implant material.

Superparamagnetic iron oxide nanoparticles (SPION) for the treatment of antibiotic-resistant biofilms.

Bacterial infections caused by antibiotic-resistant strains are of deep concern due to an increasing prevalence, and are a major cause of morbidity in the United States of America. In particular, medical device failures, and thus human lives, are greatly impacted by infections, where the treatments required are further complicated by the tendency of pathogenic bacteria, such as Staphylococcus aureus, to produce antibiotic resistant biofilms. In this study, a panel of relevant antibiotics used clinically including penicillin, oxacillin, gentamicin, streptomycin, and vancomycin are tested, and although antibiotics are effective against free-floating planktonic S. aureus, either no change in biofilm function is observed, or, more frequently, biofilm function is enhanced. As an alternative, superparamagnetic iron oxide nanoparticles (SPION) are synthesized through a two-step process with dimercaptosuccinic acid as a chelator, followed by the conjugation of metals including iron, zinc, and silver; thus, the antibacterial properties of the metals are coupled to the superparamagnetic properties of SPION. SPION might be the ideal antibacterial treatment, with a superior ability to decrease multiple bacterial functions, target infections in a magnetic field, and had activity better than antibiotics or metal salts alone, as is required for the treatment of medical device infections for which no treatment exists today.

Fructose-enhanced reduction of bacterial growth on nanorough surfaces.

Patients on mechanical ventilators for extended periods of time often face the risk of developing ventilator-associated pneumonia. During the ventilation process, patients incapable of breathing are intubated with polyvinyl chloride (PVC) endotracheal tubes (ETTs). PVC ETTs provide surfaces where bacteria can attach and proliferate from the contaminated oropharyngeal space to the sterile bronchoalveolar area. To overcome this problem, ETTs can be coated with antimicrobial agents. However, such coatings may easily delaminate during use. Recently, it has been shown that changes in material topography at the nanometer level can provide antibacterial properties. In addition, some metabolites, such as fructose, have been found to increase the efficiency of antibiotics used to treat Staphylococcus aureus (S. aureus) infections. In this study, we combined the antibacterial effect of nanorough ETT topographies with sugar metabolites to decrease bacterial growth and biofilm formation on ETTs. We present for the first time that the presence of fructose on the nanorough surfaces decreases the number of planktonic S. aureus bacteria in the solution and biofilm formation on the surface after 24 hours. We thus envision that this method has the potential to impact the future of surface engineering of biomaterials leading to more successful clinical outcomes in terms of longer ETT lifetimes, minimized infections, and decreased antibiotic usage; all of which can decrease the presence of antibiotic resistant bacteria in the clinical setting.

Decreased Staphylococcus aureus biofilm growth on anodized nanotubular titanium and the effect of electrical stimulation.

Infection is a major problem in orthopedics leading to implant failure. It is a challenging task to treat orthopedic implant infection, which may lead to implant replacement and, in severe cases, may result in amputation and mortality. Infection poses an even further risk as bacteria are beginning to develop resistance against commonly used antibiotics. Therefore, in this research a combination of various approaches was used to fight implant infection without resorting to the use of antibiotics. Specifically, conventional titanium was altered through a process of anodization and electrical stimulation to reduce Staphylococcus aureus growth. It was shown that when a 15-30 V electrical stimulation was coupled with anodized nanotubular titanium a significant decrease in S. aureus biofilm formation was observed, compared with non-anodized and non-electrically stimulated titanium after 2 days culture. The decrease in biofilm formation observed here was explained by the presence of fluorine on the surfaces of anodized nanotubular titanium. Thus, coupling the positive influences of anodization and electrical stimulation could be a promising way to fight titanium-based orthopedic device-related infections.