Influence of excipients on characteristics and release profiles of poly(epsilon-caprolactone) microspheres containing immunoglobulin G

Protein instability during microencapsulation has been one of the major drawbacks of protein delivery systems. In this study, the effects of various excipients (poly vinyl alcohol, glucose, starch, heparin) on the stability of encapsulated human immunoglobulin G (IgG) in poly(epsilon-caprolactone) (PCL) microspheres and on microsphere characteristics were investigated before and after gamma-sterilization. Microspheres formulated without any excipients and with glucose had a mean particle size around 3-4 mu m whereas the mean particle sizes of other microspheres were around 5-6 mu m. Use of PVA significantly increased the IgG-loading and encapsulation efficiency of microspheres. After gamma-irradiation, IgG stability was mostly maintained in the microspheres with excipients compared to microspheres without any excipients. According to the mu BCA results, microspheres without any excipient showed a high initial burst release as well as a fast release profile among all groups. Presence of PVA decreased the loss in the activity of IgG released before (completely retained after 6 h and 15.69% loss after 7 days) and after gamma-irradiation (26.04% loss and 52.39% loss after 6 h and 7 days, respectively). The stabilization effect of PVA on the retention of the activity of released IgG was found more efficient compared to other groups formulated with carbohydrates

Characteristics and release profiles of MPEG-PCL-MPEG microspheres containing immunoglobulin G

Polyester-polyether type block copolymers have attracted attention in the area of drug delivery systems with their capability in providing a broad range of amphiphilic characteristics. The aim of the present work was to prepare and characterize immunoglobulin G (IgG) loaded methoxy poly(ethylene glycol)-poly(epsilon-caprolactone)-methoxy poly(ethylene glycol) (MPEG-PCL-MPEG) microspheres as potential carrier for therapeutic monoclonal antibodies used in clinics. MPEG-PCL-MPEG triblock copolymer was synthesized by ring-opening polymerization of epsilon-caprolactone initiated by MPEG and then characterized. Microspheres were prepared by double emulsion-solvent evaporation method and their properties were compared with those of PCL microspheres. Microspheres had spherical shape with a mean particle size around 6 pm. MPEG-PCL-MPEG microspheres had higher encapsulation efficiency than PCL microspheres. After 90 days of release, 30 +/- 2% and 57 +/- 3% of the bioactivity of IgG released from non-irradiated PCL and MPEG-PCL-MPEG microspheres were protected, respectively. Presence of MPEG in microspheres provided more controlled IgG release rate and protected IgG from denaturation during gamma-irradiation (20 +/- 3% and 49 +/- 2% for PCL and MPEG-PCL-MPEG microspheres, respectively). In vitro cytotoxicity tests revealed that both MPEG-PCL-MPEG and PCL microspheres had no toxic effect on cells. This study showed that MPEG-PCL-MPEG microspheres are promising delivery systems for therapeutic monoclonal antibodies

One-pot facile synthesis of silk sericin-capped gold nanoparticles by UVC radiation: Investigation of stability, biocompatibility, and antibacterial activity

Erdemli, Ozge/0000-0001-8606-8863; GUN GOK, Zehra/0000-0001-6426-0395WOS: 000481781400001PubMed: 31393664Herein, an easy one-pot synthesis method for gold nanoparticles (AuNPs), involving only gold salt and sericin extracted from silkworm cocoon in the presence of ultraviolet C (UVC) radiation, was developed. Nanoparticle formation was confirmed by characteristic surface plasmon resonance peaks at 520-540 nm wavelengths, and the influence of silk sericin on enhancing the colloidal stability of AuNPs was confirmed. Transmission electron microscopy examination showed the average size (100%) and no sign of any detectable apoptosis or necrosis in 1-day incubation. Also, high real-time cell proliferation results of AuNPs competitive with positive control groups implied excellent in vitro biocompatibility. These results evidenced that sericin enhanced the colloidal stability of AuNPs and the biological activities of sericin-capped AuNPs reported here could render them suitable nanoscale vehicles for biomedical applications.Kirikkale University Scientific Research Projects (BAP) Coordination UnitKirikkale University [2016/141]Kirikkale University Scientific Research Projects (BAP) Coordination Unit, Grant/Award Number: 2016/14

Public Service Motivation From The Point Of View Of Teachers And School Administrators: A Qualitative Study

Teachers and school administrators as public servants are people who devote themselves to the education of young people and raise up future generations. Due to their role in the transformation of the society and building of the future for new generations, it is important to what extent they adopt the ideals and motivation of public service. In this study, it is aimed to investigate how teachers and school administrators working in public primary and secondary schools conceptualize the public service motivation. The study was designed as qualitative research and the data were collected through interviews with teachers and administrators who worked at public schools for at least five years. Data were analyzed by using NVivo 10 package program and content analysis method. According to the findings obtained in the study, what participants understand from the concept of “public duty”, why they have chosen to work in the public service, the challenging issues they come face to face with while performing their public service, the reasons which lower their public service motivations and the suggestions in terms of increasing the level of motivation have been explained.Wo

Clinoptilolite/PCL-PEG-PCL composite scaffolds for bone tissue engineering applications

The aim of this study was to prepare and characterize highly porous clinoptilolite/poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) composite scaffolds. Scaffolds with different clinoptilolite contents (10% and 20%) were fabricated with reproducible solvent-free powder compression/particulate leaching technique. The scaffolds had interconnective porosity in the range of 55-76%. Clinoptilolite/poly(epsilon-caprolactone)-poly(ethylene glycol)poly(epsilon-caprolactone) scaffolds showed negligible degradation within eight weeks and displayed less water uptake and higher bioactivity than poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) scaffolds. The presence of clinoptilolite improved the mechanical properties. Highest compressive strength (5.6 MPa) and modulus (114.84 MPa) were reached with scaffold group containing 20% clinoptilolite. In vitro protein adsorption capacity of the scaffolds was also higher for clinoptilolite/poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) scaffolds. These scaffolds had 0.95 mg protein/g scaffold adsorption capacity and also higher osteoinductivity in terms of enhanced ALP, OSP activities and intracellular calcium deposition. Stoichiometric apatite deposition (Ca/P = 1.686) was observed during cellular proliferation analysis with human fetal osteoblasts cells. Thus, it can be suggested that clinoptilolite/poly(epsilon-caprolactone)poly(ethylene glycol)-poly(epsilon-caprolactone) composite scaffolds could be promising carriers for enhancement of bone regeneration in bone tissue engineering applications

Synthesis and characterization of sericin-capped gold nanoparticles

Erdemli, Ozge/0000-0001-8606-8863;WOS: 000435972700023In this study, sericin-capped gold nanoparticles (S-AuNP) were synthesized by using the silk sericin isolated from Bombyx mori silkworm cocoon. Sericin solutions having different concentrations (0.25%, 0.5 ve 1) and pH values (8 and 12) were added to fixed amount of gold salt (1 mM) to obtain experimental groups (S-AuNP0.25, S-AuNP0.5, S-AuNP1). Red color shift and distinct surface plasmon resonance (SPR) peaks observed at 520-530 nm wavelenghts in all groups were indicative of nanoparticle synthesis. However, these red color shift and peaks were not clear in pH 12. According to FTIR analyses, N-H, O-H and C=0 functional groups of sericin might have played a role in reduction reaction. In TEM images, both the average particle size and distribution of S-AuNPs increased with increasing sericin concentration. Sericin rendered the surface charge of nanoparticles negative and the increase in negative zeta potential of S-AuNP0.5 and S-AuNP1 showed that they were more stable in water than S-AuNP0.25. This result was confirmed with stability in salt experiments. S-AuNP0.25 lost its stability in salt after 1 day incubation, but the other groups remained stable as long as 7 days. As a whole, the most convenient group was assumed to be S-AuNP0,5. Such nanoparticles sythesized in this manner could have potential applications in biomedical sector such as nanosized drug delivery systems and so on

In vitro/in vivo comparison of cefuroxime release from poly(epsilon-caprolactone)-calcium sulfate implants for osteomyelitis treatment

This study aimed to investigate the release of cefuroxime axetil (CF) and calcium from poly(epsilon-caprolactone) (PCL)-calcium sulfate (CaS) implants (PCL:CaS 2:1-10% CF; PCL:CaS 2:1-20% CF; PCL:CaS 1:1-10% CF) for treating infectious bone diseases. Bioactivity, crystallinity and strength, and release profiles under standard and pressurized release conditions were studied. PCL:CaS 2:1-20% CF had slower release than 10% loading. These groups had no significant change in CF and Ca release in response to pressure. The PCL:CaS 1:1 group had the slowest release despite having higher CaS, probably due to more compaction of discs. In contrast, pressure caused significant differentiation of CF and Ca2+ release. The presence of CaS enhanced mechanical properties and bioactivity of discs. SEM and XPS results showed calcium-phosphate containing accumulations on surfaces upon SBF incubation. CF-loaded implants were applied in a rabbit osteomyelitis model. In vivoCF release was enhanced with increased CaS proportions, suggesting that in vivo release conditions are closer to pressurized in vitro conditions. In the control group, there was still some inflammation in the bone and no complete coverage with bone was achieved in the defect site. Discs provided a suitable surface for regeneration of bone. However, bone formation in the PCL:CaS 1:1 disc implanted group was more complete and regular than in the 2:1 group. (C) 2013 International Union of Biochemistry and Molecular Biology, Inc. Volume 60, Number 6, Pages 603-616, 201

Composite clinoptilolite/PCL-PEG-PCL scaffolds for bone regeneration: In vitro and in vivo evaluation

In this study, clinoptilolite (CLN) was employed as a reinforcement in a polymer-based composite scaffold in bone tissue engineering and evaluated in vivo for the first time. Highly porous, mechanically stable, and osteogenic CLN/PCL-PEG-PCL (CLN/PCEC) scaffolds were fabricated with modified particulate leaching/compression molding technique with varying CLN contents. We hypothesized that CLN reinforcement in a composite scaffold will improve bone regeneration and promote repair. Therefore, the scaffolds were analyzed for compressive strength, biodegradation, biocompatibility, and induction of osteogenic differentiation in vitro. CLN inclusion in PC-10 (10% w/w) and PC-20 (20% w/w) scaffolds revealed 54.7% and 53.4% porosity, higher dry (0.62 and 0.76 MPa), and wet (0.37 and 0.45 MPa) compressive strength, greater cellular adhesion, alkaline phosphatase activity (2.20 and 2.82 mg/g(DNA)/min), and intracellular calcium concentration (122.44 and 243.24 g Ca/mg(DNA)). The scaffolds were evaluated in a unicortical bone defect at anterior aspect of proximal tibia of adult rabbits 4 and 8 weeks postimplantation. Similar to in vitro results, CLN-containing scaffolds led to efficient regeneration of bone in a dose-dependent manner. PC-20 demonstrated highest quality of bone union, cortex development, and bone-scaffold interaction at the defect site. Therefore, higher CLN content in PC-20 permitted robust remodeling whereas pure PCEC (PC-0) scaffolds displayed fibrous tissue formation. Consequently, CLN was proven to be a potent reinforcement in terms of promoting mechanical, physical, and biological properties of polymer-based scaffolds in a more economical, easy-to-handle, and reproducible approach

In vitro evaluation of effects of sustained anti-TNF release from MPEG-PCL-MPEG and PCL microspheres on human rheumatoid arthritis synoviocytes

Anti-tumor necrosis factor (TNF) drugs such as etanercept (ETN) have been mostly used in systemic treatment of rheumatoid arthritis. To eliminate the side effects in long-term treatments and to achieve a local sustained anti-inflammatory effect, a controlled drug delivery system is needed for anti-TNF drugs. This study aims to develop novel injectable microcarriers of ETN that can provide long-term controlled release of this protein drug upon intra-articular application. In this study, poly(epsilon-caprolactone) (PCL) and its copolymer with poly(ethylene glycol), methoxypoly(ethylene glycol)-poly(epsilon-caprolactone)-methoxypoly(ethylene glycol) microspheres (MPEG-PCL-MPEG) were compared for their prospective success in rheumatoid arthritis treatment. Microspheres with smooth surface of a mean particle diameter of approximately 5m were prepared with both polymers. MPEG-PCL-MPEG microspheres had higher encapsulation efficiency than PCL microspheres. The activity of encapsulated ETN within MPEG-PCL-MPEG microspheres also retained while 90% of the activity of ETN within PCL microspheres could retain during 90-day release. MPEG-PCL-MPEG microspheres showed faster ETN release compared to PCL microspheres in various release media. Cumulative amounts of ETN released from both types of microspheres were significantly lower in cell culture medium and in synovial fluids than in phosphate buffered saline. This was mainly due to protein adsorption onto microspheres. Hydrophilic MPEG segment enhanced ETN release while preventing protein adsorption on microspheres compared to PCL. Sustained ETN release from microspheres resulted with a significant decrease in pro-inflammatory cytokines (TNF, IFN, IL-6, IL-17) and MMP levels (MMP-3, MMP-13), while conserving viability of fibroblast-like synoviocytes compared to the free drug. Results suggest that MPEG-PCL-MPEG is a potential copolymer of PCL that can be used in development of biomedical materials for effective local treatment purposes in chronic inflammatory arthritis owing to enhanced hydrophilicity. Yet, PCL microspheres are also promising systems having good compatibility to synoviocytes and would be especially the choice for treatment approach requiring longer term and slower release

On the Infectivity of Bacteriophages in Polyelectrolyte Multilayer Films: Inhibition or Preservation of Their Bacteriolytic Activity?

International audienc