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Injectable gellan gum-based nanoparticles-loaded system for the local delivery of vancomycin in osteomyelitis treatment.

Posadowska U, Brzychczy-Wloch M, Pamula E - J Mater Sci Mater Med (2015)

Bottom Line: The resulting system was found to be injectable (extrusion force 11.3 ± 1.1 N), reassembled its structure after breaking as shown by rheology tests and ensured required burst release followed by sustained Vanc delivery.The system was cytocompatible with osteoblast-like MG-63 cells (no significant impact on cells' viability was detected).As a result we obtained a biocompatible system displaying ease of application (low extrusion force), self-healing ability after disruption, adjustable drug release and antimicrobial properties.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomaterials, Faculty of Materials Science and Ceramics, AGH University of Science and Technology, al. A. Mickiewicza 30, 30-059, Krakow, Poland. uposadow@agh.edu.pl.

ABSTRACT
Infection spreading in the skeletal system leading to osteomyelitis can be prevented by the prolonged administration of antibiotics in high doses. However systemic antibiotherapy, besides its inconvenience and often low efficacy, provokes numerous side effects. Thus, we formulated a new injectable nanoparticle-loaded system for the local delivery of vancomycin (Vanc) applied in a minimally-invasive way. Vanc was encapsulated in poly(L-lactide-co-glycolide) nanoparticles (NPs) by double-emulsification. The size (258 ± 11 nm), polydispersity index (0.240 ± 0.003) and surface potential (-25.9 ± 0.2 mV) of NPs were determined by dynamic light scattering and capillary electrophoresis measurements. They have a spherical morphology and a smooth topography as observed using atomic force microscopy. Vanc loading and encapsulation efficiencies were 8.8 ± 0.1 and 55.2 ± 0.5 %, respectively, based on fluorescence spectroscopy assays. In order to ensure injectability, NPs were suspended in gellan gum and cross-linked with Ca(2+); also a portion of dissolved antibiotic was added to the system. The resulting system was found to be injectable (extrusion force 11.3 ± 1.1 N), reassembled its structure after breaking as shown by rheology tests and ensured required burst release followed by sustained Vanc delivery. The system was cytocompatible with osteoblast-like MG-63 cells (no significant impact on cells' viability was detected). Growth of Staphylococcus spp. reference strains and also those isolated from osteomyelitic joints was inhibited in contact with the injectable system. As a result we obtained a biocompatible system displaying ease of application (low extrusion force), self-healing ability after disruption, adjustable drug release and antimicrobial properties.

No MeSH data available.


Related in: MedlinePlus

Metabolic activity of MG-63 cells evaluated by reduction of Alamar Blue (a) and live/dead staining (b) on 1 day or day 6 in contact with GG-Vanc-NPs extracts diluted in EMEM by the factors of 1/1, 1/2 or 1/4 and pure EMEM—Control; green are viable cells, red are dead cells (Olympus Carl Zeiss Axiovert, Germany). Scale bar 100 μm. Mean ± SEM; ***p < 0.001 (Color figure online)
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Fig5: Metabolic activity of MG-63 cells evaluated by reduction of Alamar Blue (a) and live/dead staining (b) on 1 day or day 6 in contact with GG-Vanc-NPs extracts diluted in EMEM by the factors of 1/1, 1/2 or 1/4 and pure EMEM—Control; green are viable cells, red are dead cells (Olympus Carl Zeiss Axiovert, Germany). Scale bar 100 μm. Mean ± SEM; ***p < 0.001 (Color figure online)

Mentions: Metabolic activity studies performed on MG-63 osteoblast-like cells on day 1 and 6 showed that cell function was not significantly altered by incubation in GG-Vanc-NPs extracts (Fig. 5a). Regarding more concentrated extracts, a slight tendency to down regulate cells’ activity was seen, but the differences were not significant. On day 6 the cells increased their activity significantly as compared to day 1.


Injectable gellan gum-based nanoparticles-loaded system for the local delivery of vancomycin in osteomyelitis treatment.

Posadowska U, Brzychczy-Wloch M, Pamula E - J Mater Sci Mater Med (2015)

Metabolic activity of MG-63 cells evaluated by reduction of Alamar Blue (a) and live/dead staining (b) on 1 day or day 6 in contact with GG-Vanc-NPs extracts diluted in EMEM by the factors of 1/1, 1/2 or 1/4 and pure EMEM—Control; green are viable cells, red are dead cells (Olympus Carl Zeiss Axiovert, Germany). Scale bar 100 μm. Mean ± SEM; ***p < 0.001 (Color figure online)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4666281&req=5

Fig5: Metabolic activity of MG-63 cells evaluated by reduction of Alamar Blue (a) and live/dead staining (b) on 1 day or day 6 in contact with GG-Vanc-NPs extracts diluted in EMEM by the factors of 1/1, 1/2 or 1/4 and pure EMEM—Control; green are viable cells, red are dead cells (Olympus Carl Zeiss Axiovert, Germany). Scale bar 100 μm. Mean ± SEM; ***p < 0.001 (Color figure online)
Mentions: Metabolic activity studies performed on MG-63 osteoblast-like cells on day 1 and 6 showed that cell function was not significantly altered by incubation in GG-Vanc-NPs extracts (Fig. 5a). Regarding more concentrated extracts, a slight tendency to down regulate cells’ activity was seen, but the differences were not significant. On day 6 the cells increased their activity significantly as compared to day 1.

Bottom Line: The resulting system was found to be injectable (extrusion force 11.3 ± 1.1 N), reassembled its structure after breaking as shown by rheology tests and ensured required burst release followed by sustained Vanc delivery.The system was cytocompatible with osteoblast-like MG-63 cells (no significant impact on cells' viability was detected).As a result we obtained a biocompatible system displaying ease of application (low extrusion force), self-healing ability after disruption, adjustable drug release and antimicrobial properties.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomaterials, Faculty of Materials Science and Ceramics, AGH University of Science and Technology, al. A. Mickiewicza 30, 30-059, Krakow, Poland. uposadow@agh.edu.pl.

ABSTRACT
Infection spreading in the skeletal system leading to osteomyelitis can be prevented by the prolonged administration of antibiotics in high doses. However systemic antibiotherapy, besides its inconvenience and often low efficacy, provokes numerous side effects. Thus, we formulated a new injectable nanoparticle-loaded system for the local delivery of vancomycin (Vanc) applied in a minimally-invasive way. Vanc was encapsulated in poly(L-lactide-co-glycolide) nanoparticles (NPs) by double-emulsification. The size (258 ± 11 nm), polydispersity index (0.240 ± 0.003) and surface potential (-25.9 ± 0.2 mV) of NPs were determined by dynamic light scattering and capillary electrophoresis measurements. They have a spherical morphology and a smooth topography as observed using atomic force microscopy. Vanc loading and encapsulation efficiencies were 8.8 ± 0.1 and 55.2 ± 0.5 %, respectively, based on fluorescence spectroscopy assays. In order to ensure injectability, NPs were suspended in gellan gum and cross-linked with Ca(2+); also a portion of dissolved antibiotic was added to the system. The resulting system was found to be injectable (extrusion force 11.3 ± 1.1 N), reassembled its structure after breaking as shown by rheology tests and ensured required burst release followed by sustained Vanc delivery. The system was cytocompatible with osteoblast-like MG-63 cells (no significant impact on cells' viability was detected). Growth of Staphylococcus spp. reference strains and also those isolated from osteomyelitic joints was inhibited in contact with the injectable system. As a result we obtained a biocompatible system displaying ease of application (low extrusion force), self-healing ability after disruption, adjustable drug release and antimicrobial properties.

No MeSH data available.


Related in: MedlinePlus