Prolonged antimicrobial activity of PMMA bone cement with embedded gentamicin-releasing silica nanocarriers

Antibiotic laden bone cements are regularly employed to prevent infections after joint replacement surgeries. We have developed silica nanocarriers loaded with gentamicin as a drug delivery system to be dispersed in poly methyl-methacrylate (PMMA) bone cement for controlling and extending the release of the antibiotic from bone cements, thus proving a prolonged antimicrobial activity. Layer-by-layer self-assembly was used to deposit gentamicin between alginate layers and two different poly β-amino esters on the silica nanoparticles. The release of gentamicin from PMMA bone cement containing silica nanocarriers continued for about 30 days compared to 6 days when the same amount of antibiotic was added as a pure powder (as in commercial formulations); moreover, the medium containing the released antimicrobial drug was capable of preventing the growth of numerous bacteria species responsible for prosthetic joint infections (both catalogue strains and clinical isolates) for longer periods of time than in the case of commercial formulations, thus confirming the extended antimicrobial properties of the drug once released from the carrier. No detrimental effects toward human osteoblasts were also observed; moreover, bone cement material characteristics such as curing time, water uptake, and mechanical properties were unaffected when the silica nanocarriers were added

Prevention of biofilm accumulation on a light-activated antimicrobial catheter material

The colonization of catheters by microorganisms is a serious problem that can lead to the development of resistant biofilm-related infections. Lethal photosensitisation is a possible solution as it is capable of inactivating microorganisms through the generation of reactive oxygen species. Previously we have shown that a Methylene Blue and gold nanoparticle-embedded silicone material has antimicrobial properties against planktonic bacteria when exposed to laser light. In this work the material has been tested for its ability to reduce the formation of Staphylococcus epidermidis biofilms. Biofilm formation was observed over time using a flow cell which was arranged to allow laser irradiation in situ. The duration and frequency of light exposure were changed so that the same amount of energy was delivered during each experiment. Neither short (5 min) but frequent (every 30 min) irradiation nor long (20 min) and infrequent (every 120 min) exposure was able to significantly prevent biofilm formation; they resulted in 75% and 60%, respectively, of the surface covered by the biofilm after 6 hour of colonization compared to 100% coverage when no laser was used. However, when laser irradiation was performed for 10 min every 60 min, a reduction in biofilm coverage of greater than 50% was observed compared to untreated silicone. The properties of the materials post-irradiation were also evaluated; the surface roughness of the material, the asperity density and the asperity height showed a continuous decrease with energy dose. However, the elasticity (Young's module) was not affected by the irradiation. This appears to be a promising novel light-activated material which, as well as displaying antimicrobial activity, has been shown for the first time capable of reducing biofilm formation over time

Clinical and immunophenotypic aspects of common variable immunodeficiency in adults

Features of expression of differentiation markers of peripheral blood lymphocytes were studied by flow cytofluorimetry in combination with clinical manifestations in 30 adult patients (12 men and 18 women, mean age 37.5±12.3 years) with the established diagnosis of сommon variable immunodeficiency (CVID). The examination of patients was carried out in the period of obvious absence of infectious and inflammatory diseases. It was found that the dominant immunophenotype in adult patients with СVID is an increase in the blood content of T cytotoxic lymphocytes (CD3+CD8+) with high expression of activation markers HLA- DR+ and CD38+ and a decrease in isotype-switched B lymphocytes IgD-27+ (in almost 100% of the examined individuals). The maximum degree of increase in the number of T killers was observed in patients with a low level of B lymphocytes (CD19+ less than 6%, p = 0.005) and a minimum concentration of IgG in the blood serum (less than 2 g/l, p = 0.02). The content of isotype-switched B cells correlated with the level of IgG, as well as the total concentration of serum immunoglobulins A, M and G (p = 0.02; p = 0.003). In adult СVID patients with the combined clinical phenotype “infectious syndrome + autoimmune disease”, the content of isotype-switched B lymphocytes, IgG and the total concentration of Ig in the blood is significantly lower (p = 0.04; p = 0.03 and p = 0.02), and activated T killers with HLA-DR+ and CD38+ expression are higher (p% = 0.01; rabs = 0.02 and p% = 0.004; rabs = 0.001, respectively) compared to patients with isolated infectious – inflammatory syndrome. We also found that among patients with the lowest number of isotype-switched IgD- 27+ B cells (less than 5%) and serum IgG concentration (less than 2 g/l), the incidence of lymphoproliferative syndrome is higher (p = 0.04 and p = 0.01, respectively). Thus, the low content of isotype-switched memory B lymphocytes in peripheral blood is most characteristic of patients with a more severe clinical phenotype of СVID