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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

Vanc release profiles from a Vanc-loaded nanoparticles (1 ml of 0.1 % w/v NPs suspension, antibiotic content 0.9 mg) b gellan gum with antibiotic (1 ml of GG-Vanc, antibiotic content 1.0 mg) and c injectable system (1 ml of GG-Vanc-NPs, antibiotic content 1.9 mg). Merged pictures presenting cumulative release (left axes, squares) and 10-day doses (right axes, bars)
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Fig3: Vanc release profiles from a Vanc-loaded nanoparticles (1 ml of 0.1 % w/v NPs suspension, antibiotic content 0.9 mg) b gellan gum with antibiotic (1 ml of GG-Vanc, antibiotic content 1.0 mg) and c injectable system (1 ml of GG-Vanc-NPs, antibiotic content 1.9 mg). Merged pictures presenting cumulative release (left axes, squares) and 10-day doses (right axes, bars)

Mentions: For NPs (Fig. 3a) an initial burst release on day 1 amounting to ~260 μg was measured, which was ~26 % of the total encapsulated antibiotic. Thereafter, the delivery was more sustained: 220–100 μg/10-day interval (in total ~83 % of the whole Vanc dose was liberated within 40 days). For GG-Vanc (Fig. 3b), a burst release after day 1 was also observed, which amounted to ~340 μg (~34 % of total encapsulated antibiotic). Thereafter, the release kinetics were less sustained than for NPs: the delivered amount varied between 110 and 10 μg/10-day interval and the whole Vanc dose almost exhausted up to day 20. For GG-Vanc-NPs (Fig. 3c) a burst release of ~900 μg (~47 % of Vanc content) was obtained that was followed by balanced delivery of ~120 μg/10-day interval. Up to day 40 a sustained delivery phase was observed. In total, the system delivered ~1.5 mg, i.e. ~80 % of Vanc.


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)

Vanc release profiles from a Vanc-loaded nanoparticles (1 ml of 0.1 % w/v NPs suspension, antibiotic content 0.9 mg) b gellan gum with antibiotic (1 ml of GG-Vanc, antibiotic content 1.0 mg) and c injectable system (1 ml of GG-Vanc-NPs, antibiotic content 1.9 mg). Merged pictures presenting cumulative release (left axes, squares) and 10-day doses (right axes, bars)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: Vanc release profiles from a Vanc-loaded nanoparticles (1 ml of 0.1 % w/v NPs suspension, antibiotic content 0.9 mg) b gellan gum with antibiotic (1 ml of GG-Vanc, antibiotic content 1.0 mg) and c injectable system (1 ml of GG-Vanc-NPs, antibiotic content 1.9 mg). Merged pictures presenting cumulative release (left axes, squares) and 10-day doses (right axes, bars)
Mentions: For NPs (Fig. 3a) an initial burst release on day 1 amounting to ~260 μg was measured, which was ~26 % of the total encapsulated antibiotic. Thereafter, the delivery was more sustained: 220–100 μg/10-day interval (in total ~83 % of the whole Vanc dose was liberated within 40 days). For GG-Vanc (Fig. 3b), a burst release after day 1 was also observed, which amounted to ~340 μg (~34 % of total encapsulated antibiotic). Thereafter, the release kinetics were less sustained than for NPs: the delivered amount varied between 110 and 10 μg/10-day interval and the whole Vanc dose almost exhausted up to day 20. For GG-Vanc-NPs (Fig. 3c) a burst release of ~900 μg (~47 % of Vanc content) was obtained that was followed by balanced delivery of ~120 μg/10-day interval. Up to day 40 a sustained delivery phase was observed. In total, the system delivered ~1.5 mg, i.e. ~80 % of Vanc.

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