In vitro and in vivo performance of nanosized hydroxyapatite particles coated with poly-dl-lactide-co-glycolide as systems for drug delivery of tigecycline
Authors
Ignjatović, Nenad
Ninkov, Petar
Sabetrasekh, Roya
Lyngstadaas, Staale Petter
Uskoković, Dragan

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Calcium-phosphate/poly(dl-lactide-co-glycolide) (CP/PLGA) composite biomaterial in granular form showed a high potential in the reconstruction of bone tissue. Compared to pure polymers, the combination of CP with biodegradable polymers used in bone drug delivery systems shows certain advantages. Composite biomaterials in nano particulate (NPs) form may have significant advantages over those in micro- or submicro-particulate form. The purpose of the study presented in this paper has been to examine the possibility of the synthesis of a new nanoparticulate system for controlled and systemic drug delivery with double effect. In the first step, a drug is released from bioresorbable polymer; in the second stage, after resorption of the polymer, non-bioresorbable calcium phosphate remains the chief part of the particle and takes the role of a filler, filling a bone defect. The obtained tigecycline-loaded calcium-phosphate(CP)/poly(dl-lactide-co-glycolide)(PLGA) nano particles contain calcium... phosphate coated with bioresorbable polymer and 0.6, 2 and 5wt% tigecycline. The composite was analyzed by FT-IR, XRD, HPLC and AFM methods. The average particle size of the nanocomposite increases with the augmentation of the part of antibiotics, and it ranges from 65 to 95 nm. Release profiles of tigecycline were obtained by UV-VIS spectroscopy in physiological solution at 37oC. Experimental results were analyzed using Peppas and Weibull mathematical models. Based on kinetic parameters, tigecycline release was defined as non-Fickian transport. The in vitro cytotoxicity of the nanocomposite was examined on standard cell lines of MC3T3-E1, in vitro. The obtained low values of LDH activity (under 37%) indicate low cytotoxicity level. Inhibition of bacteria in aerobic and anaerobic conditions in vitro was analyzed after 1, 2 and 3 weeks. The behaviour of the composite under real-life conditions was analyzed through implantation of the nanocomposite into living organisms, in vivo. The system with the lowest tigecycline content proved to be an adequate system for local and controlled release.
Keywords:
Calcium-phosphate/poly(dl-lactide-co-glycolide) / CP/PLGA / composite biomaterials / bone tissue reconstructionSource:
Programme and The Book of Abstracts / Eleventh Annual Conference YUCOMAT 2009, Herceg Novi, August 31 – September 4, 2009, 2009, 71-71Publisher:
- Belgrade : Institute of Technical Sciences of SASA
Funding / projects:
- Sinteza funkcionalnih materijala sa kontrolisanom strukturom na molekularnom i nano nivou (RS-142006)
Institution/Community
Институт техничких наука САНУ / Institute of Technical Sciences of SASATY - CONF AU - Ignjatović, Nenad AU - Ninkov, Petar AU - Sabetrasekh, Roya AU - Lyngstadaas, Staale Petter AU - Uskoković, Dragan PY - 2009 UR - https://dais.sanu.ac.rs/123456789/4932 AB - Calcium-phosphate/poly(dl-lactide-co-glycolide) (CP/PLGA) composite biomaterial in granular form showed a high potential in the reconstruction of bone tissue. Compared to pure polymers, the combination of CP with biodegradable polymers used in bone drug delivery systems shows certain advantages. Composite biomaterials in nano particulate (NPs) form may have significant advantages over those in micro- or submicro-particulate form. The purpose of the study presented in this paper has been to examine the possibility of the synthesis of a new nanoparticulate system for controlled and systemic drug delivery with double effect. In the first step, a drug is released from bioresorbable polymer; in the second stage, after resorption of the polymer, non-bioresorbable calcium phosphate remains the chief part of the particle and takes the role of a filler, filling a bone defect. The obtained tigecycline-loaded calcium-phosphate(CP)/poly(dl-lactide-co-glycolide)(PLGA) nano particles contain calcium phosphate coated with bioresorbable polymer and 0.6, 2 and 5wt% tigecycline. The composite was analyzed by FT-IR, XRD, HPLC and AFM methods. The average particle size of the nanocomposite increases with the augmentation of the part of antibiotics, and it ranges from 65 to 95 nm. Release profiles of tigecycline were obtained by UV-VIS spectroscopy in physiological solution at 37oC. Experimental results were analyzed using Peppas and Weibull mathematical models. Based on kinetic parameters, tigecycline release was defined as non-Fickian transport. The in vitro cytotoxicity of the nanocomposite was examined on standard cell lines of MC3T3-E1, in vitro. The obtained low values of LDH activity (under 37%) indicate low cytotoxicity level. Inhibition of bacteria in aerobic and anaerobic conditions in vitro was analyzed after 1, 2 and 3 weeks. The behaviour of the composite under real-life conditions was analyzed through implantation of the nanocomposite into living organisms, in vivo. The system with the lowest tigecycline content proved to be an adequate system for local and controlled release. PB - Belgrade : Institute of Technical Sciences of SASA C3 - Programme and The Book of Abstracts / Eleventh Annual Conference YUCOMAT 2009, Herceg Novi, August 31 – September 4, 2009 T1 - In vitro and in vivo performance of nanosized hydroxyapatite particles coated with poly-dl-lactide-co-glycolide as systems for drug delivery of tigecycline SP - 71 EP - 71 UR - https://hdl.handle.net/21.15107/rcub_dais_4932 ER -
@conference{ author = "Ignjatović, Nenad and Ninkov, Petar and Sabetrasekh, Roya and Lyngstadaas, Staale Petter and Uskoković, Dragan", year = "2009", abstract = "Calcium-phosphate/poly(dl-lactide-co-glycolide) (CP/PLGA) composite biomaterial in granular form showed a high potential in the reconstruction of bone tissue. Compared to pure polymers, the combination of CP with biodegradable polymers used in bone drug delivery systems shows certain advantages. Composite biomaterials in nano particulate (NPs) form may have significant advantages over those in micro- or submicro-particulate form. The purpose of the study presented in this paper has been to examine the possibility of the synthesis of a new nanoparticulate system for controlled and systemic drug delivery with double effect. In the first step, a drug is released from bioresorbable polymer; in the second stage, after resorption of the polymer, non-bioresorbable calcium phosphate remains the chief part of the particle and takes the role of a filler, filling a bone defect. The obtained tigecycline-loaded calcium-phosphate(CP)/poly(dl-lactide-co-glycolide)(PLGA) nano particles contain calcium phosphate coated with bioresorbable polymer and 0.6, 2 and 5wt% tigecycline. The composite was analyzed by FT-IR, XRD, HPLC and AFM methods. The average particle size of the nanocomposite increases with the augmentation of the part of antibiotics, and it ranges from 65 to 95 nm. Release profiles of tigecycline were obtained by UV-VIS spectroscopy in physiological solution at 37oC. Experimental results were analyzed using Peppas and Weibull mathematical models. Based on kinetic parameters, tigecycline release was defined as non-Fickian transport. The in vitro cytotoxicity of the nanocomposite was examined on standard cell lines of MC3T3-E1, in vitro. The obtained low values of LDH activity (under 37%) indicate low cytotoxicity level. Inhibition of bacteria in aerobic and anaerobic conditions in vitro was analyzed after 1, 2 and 3 weeks. The behaviour of the composite under real-life conditions was analyzed through implantation of the nanocomposite into living organisms, in vivo. The system with the lowest tigecycline content proved to be an adequate system for local and controlled release.", publisher = "Belgrade : Institute of Technical Sciences of SASA", journal = "Programme and The Book of Abstracts / Eleventh Annual Conference YUCOMAT 2009, Herceg Novi, August 31 – September 4, 2009", title = "In vitro and in vivo performance of nanosized hydroxyapatite particles coated with poly-dl-lactide-co-glycolide as systems for drug delivery of tigecycline", pages = "71-71", url = "https://hdl.handle.net/21.15107/rcub_dais_4932" }
Ignjatović, N., Ninkov, P., Sabetrasekh, R., Lyngstadaas, S. P.,& Uskoković, D.. (2009). In vitro and in vivo performance of nanosized hydroxyapatite particles coated with poly-dl-lactide-co-glycolide as systems for drug delivery of tigecycline. in Programme and The Book of Abstracts / Eleventh Annual Conference YUCOMAT 2009, Herceg Novi, August 31 – September 4, 2009 Belgrade : Institute of Technical Sciences of SASA., 71-71. https://hdl.handle.net/21.15107/rcub_dais_4932
Ignjatović N, Ninkov P, Sabetrasekh R, Lyngstadaas SP, Uskoković D. In vitro and in vivo performance of nanosized hydroxyapatite particles coated with poly-dl-lactide-co-glycolide as systems for drug delivery of tigecycline. in Programme and The Book of Abstracts / Eleventh Annual Conference YUCOMAT 2009, Herceg Novi, August 31 – September 4, 2009. 2009;:71-71. https://hdl.handle.net/21.15107/rcub_dais_4932 .
Ignjatović, Nenad, Ninkov, Petar, Sabetrasekh, Roya, Lyngstadaas, Staale Petter, Uskoković, Dragan, "In vitro and in vivo performance of nanosized hydroxyapatite particles coated with poly-dl-lactide-co-glycolide as systems for drug delivery of tigecycline" in Programme and The Book of Abstracts / Eleventh Annual Conference YUCOMAT 2009, Herceg Novi, August 31 – September 4, 2009 (2009):71-71, https://hdl.handle.net/21.15107/rcub_dais_4932 .