Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles.

Nenad Filipović, Ljiljana Veselinović, Slavica Ražić, Sanja Jeremić, Metka Filipič, Bojana Žegura, Sergej Tomić, Miodrag Čolić, Magdalena Stevanović
Author Information
  1. Nenad Filipović: Institute of Technical Sciences of the Serbian Academy of Sciences and Arts, Knez Mihailova 35/IV, 11000 Belgrade, Serbia.
  2. Ljiljana Veselinović: Institute of Technical Sciences of the Serbian Academy of Sciences and Arts, Knez Mihailova 35/IV, 11000 Belgrade, Serbia.
  3. Slavica Ražić: Faculty of Pharmacy - Department of Analytical Chemistry, University of Belgrade, 11000 Belgrade, Serbia.
  4. Sanja Jeremić: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11000 Belgrade, Serbia.
  5. Metka Filipič: Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, 1000 Ljubljana, Slovenia.
  6. Bojana Žegura: Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, 1000 Ljubljana, Slovenia.
  7. Sergej Tomić: Institute for the Application of Nuclear Energy, University of Belgrade, 11000 Belgrade, Serbia.
  8. Miodrag Čolić: Institute for the Application of Nuclear Energy, University of Belgrade, 11000 Belgrade, Serbia; Medical Faculty of the Military Medical Academy, University of Defence, 11000 Belgrade, Serbia.
  9. Magdalena Stevanović: Institute of Technical Sciences of the Serbian Academy of Sciences and Arts, Knez Mihailova 35/IV, 11000 Belgrade, Serbia. Electronic address: magdalena.stevanovic@itn.sanu.ac.rs.

Abstract

Poly (ε-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1-4 μm with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants.

Keywords

MeSH Term

Animals
Delayed-Action Preparations
Materials Testing
Metal Nanoparticles
Microspheres
Pancreas
Polyesters
Pseudomonas aeruginosa
Selenium
Swine

Chemicals

Delayed-Action Preparations
Polyesters
polycaprolactone
Selenium

Word Cloud

Created with Highcharts 10.0.0releaseSeNPsmicrospheresPCL/SeNPsPCLPBSnanoparticlesinvestigatedimplantwellPolyε-caprolactoneantibacterialseleniumrangedegradationsolutionPseudomonasaeruginosaPAO1extractexudateinflammatoryreactionconcentrationresultssuggestcelllineStaphylococcusATCCprolongedcarriersustainedagentdevelopedobtained1-4 μmencapsulationefficiency90%processbehaviorfivedifferentmedia:phosphatebufferlipaseisolatedporcinepancreas01 MhydrochloricacidHClcell-freefluidsubcutaneouslyimplantedsterilepolyvinylspongesinduceforeign-bodysamplesthoroughlycharacterizedSEMTEMFTIRXRDPSADSCconfocalmicroscopyICP-OEStechniquesphysiologicalconditionsneutralpHslowoccurred38%casePBS + lipaserespectively660 daysacidicenvironmentpresencedetectedhandmediumbacterialmuchpronouncedeven24 h13%7 daysreachedmaximumaround30%Also37%released11 daysincubationtriggeredbacteriumforeignbodyFurthermoretermsbiocompatibilitypurposecytotoxicityformationreactiveoxygenspeciesROSgenotoxicityevaluatedHepG2interactionphagocyticRaw2647macrophagesmonitoredfoundacutecytotoxiceffectsFinallyshowedconsiderableactivityGram-positivebacteria:aureus25923epidermidis1228PCL/SeNPs-basedsystemattractiveplatformpreventioninfectionsaccompanyingimplantsBiodegradationMicrospheresProlongedSelenium

Similar Articles

Cited By