Using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo
Chunyan Qiao,1,* Kai Zhang,2,* Han Jin,1 Leiying Miao,3 Ce Shi,1 Xia Liu,1 Anliang Yuan,1 Jinzhong Liu,1 Daowei Li,1 Changyu Zheng,4 Guirong Zhang,5 Xiangwei Li,1 Bai Yang,2 Hongchen Sun11Department of Pathology, School of Stomatology, Jilin University, Changchun, 2State Key Laboratory of Supramolec...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/bbfcbb6400da4f049d0c097dfa11b630 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:bbfcbb6400da4f049d0c097dfa11b630 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:bbfcbb6400da4f049d0c097dfa11b6302021-12-02T00:37:47ZUsing poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo1176-91141178-2013https://doaj.org/article/bbfcbb6400da4f049d0c097dfa11b6302013-08-01T00:00:00Zhttp://www.dovepress.com/using-polylactic-co-glycolic-acid-microspheres-to-encapsulate-plasmid--a14022https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Chunyan Qiao,1,* Kai Zhang,2,* Han Jin,1 Leiying Miao,3 Ce Shi,1 Xia Liu,1 Anliang Yuan,1 Jinzhong Liu,1 Daowei Li,1 Changyu Zheng,4 Guirong Zhang,5 Xiangwei Li,1 Bai Yang,2 Hongchen Sun11Department of Pathology, School of Stomatology, Jilin University, Changchun, 2State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 3Institute and Hospital of Stomatology, Nanjing University Medical School, Nanjing, People's Republic of China; 4Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA; 5Department of Biochemistry, School of Basic Medicine, Jilin University, Changchun, People's Republic of China*These authors contributed equally to this workAbstract: Repair of large bone defects is a major challenge, requiring sustained stimulation to continually promote bone formation locally. Bone morphogenetic protein 2 (BMP-2) plays an important role in bone development. In an attempt to overcome this difficulty of bone repair, we created a delivery system to slowly release human BMP-2 cDNA plasmid locally, efficiently transfecting local target cells and secreting functional human BMP-2 protein. For transfection, we used polyethylenimine (PEI) to create pBMP-2/PEI nanoparticles, and to ensure slow release we used poly(lactic-co-glycolic acid) (PLGA) to create microsphere encapsulated pBMP-2/PEI nanoparticles, PLGA@pBMP-2/PEI. We demonstrated that pBMP-2/PEI nanoparticles could slowly release from the PLGA@pBMP-2/PEI microspheres for a long period of time. The 3–15 µm diameter of the PLGA@pBMP-2/PEI further supported this slow release ability of the PLGA@pBMP-2/PEI. In vitro transfection assays demonstrated that pBMP-2/PEI released from PLGA@pBMP-2/PEI could efficiently transfect MC3T3-E1 cells, causing MC3T3-E1 cells to secrete human BMP-2 protein, increase calcium deposition and gene expressions of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), SP7 and I type collagen (COLL I), and finally induce MC3T3-E1 cell differentiation. Importantly, in vivo data from micro-computed tomography (micro-CT) and histological staining demonstrated that the human BMP-2 released from PLGA@pBMP-2/PEI had a long-term effect locally and efficiently promoted bone formation in the bone defect area compared to control animals. All our data suggest that our PLGA-nanoparticle delivery system efficiently and functionally delivers the human BMP-2 cDNA and has potential clinical application in the future after further modification.Keywords: gene therapy, bone regeneration, biodegradable polymer, human BMP-2Qiao CZhang KJin HMiao LShi CLiu XYuan ALiu JLi DZheng CZhang GLi XYang BSun HDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 2985-2995 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine (General) R5-920 |
| spellingShingle |
Medicine (General) R5-920 Qiao C Zhang K Jin H Miao L Shi C Liu X Yuan A Liu J Li D Zheng C Zhang G Li X Yang B Sun H Using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo |
| description |
Chunyan Qiao,1,* Kai Zhang,2,* Han Jin,1 Leiying Miao,3 Ce Shi,1 Xia Liu,1 Anliang Yuan,1 Jinzhong Liu,1 Daowei Li,1 Changyu Zheng,4 Guirong Zhang,5 Xiangwei Li,1 Bai Yang,2 Hongchen Sun11Department of Pathology, School of Stomatology, Jilin University, Changchun, 2State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 3Institute and Hospital of Stomatology, Nanjing University Medical School, Nanjing, People's Republic of China; 4Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA; 5Department of Biochemistry, School of Basic Medicine, Jilin University, Changchun, People's Republic of China*These authors contributed equally to this workAbstract: Repair of large bone defects is a major challenge, requiring sustained stimulation to continually promote bone formation locally. Bone morphogenetic protein 2 (BMP-2) plays an important role in bone development. In an attempt to overcome this difficulty of bone repair, we created a delivery system to slowly release human BMP-2 cDNA plasmid locally, efficiently transfecting local target cells and secreting functional human BMP-2 protein. For transfection, we used polyethylenimine (PEI) to create pBMP-2/PEI nanoparticles, and to ensure slow release we used poly(lactic-co-glycolic acid) (PLGA) to create microsphere encapsulated pBMP-2/PEI nanoparticles, PLGA@pBMP-2/PEI. We demonstrated that pBMP-2/PEI nanoparticles could slowly release from the PLGA@pBMP-2/PEI microspheres for a long period of time. The 3–15 µm diameter of the PLGA@pBMP-2/PEI further supported this slow release ability of the PLGA@pBMP-2/PEI. In vitro transfection assays demonstrated that pBMP-2/PEI released from PLGA@pBMP-2/PEI could efficiently transfect MC3T3-E1 cells, causing MC3T3-E1 cells to secrete human BMP-2 protein, increase calcium deposition and gene expressions of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), SP7 and I type collagen (COLL I), and finally induce MC3T3-E1 cell differentiation. Importantly, in vivo data from micro-computed tomography (micro-CT) and histological staining demonstrated that the human BMP-2 released from PLGA@pBMP-2/PEI had a long-term effect locally and efficiently promoted bone formation in the bone defect area compared to control animals. All our data suggest that our PLGA-nanoparticle delivery system efficiently and functionally delivers the human BMP-2 cDNA and has potential clinical application in the future after further modification.Keywords: gene therapy, bone regeneration, biodegradable polymer, human BMP-2 |
| format |
article |
| author |
Qiao C Zhang K Jin H Miao L Shi C Liu X Yuan A Liu J Li D Zheng C Zhang G Li X Yang B Sun H |
| author_facet |
Qiao C Zhang K Jin H Miao L Shi C Liu X Yuan A Liu J Li D Zheng C Zhang G Li X Yang B Sun H |
| author_sort |
Qiao C |
| title |
Using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo |
| title_short |
Using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo |
| title_full |
Using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo |
| title_fullStr |
Using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo |
| title_full_unstemmed |
Using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo |
| title_sort |
using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo |
| publisher |
Dove Medical Press |
| publishDate |
2013 |
| url |
https://doaj.org/article/bbfcbb6400da4f049d0c097dfa11b630 |
| work_keys_str_mv |
AT qiaoc usingpolylacticcoglycolicacidmicrospherestoencapsulateplasmidofbonemorphogeneticprotein2polyethyleniminenanoparticlestopromoteboneformationinvitroandinvivo AT zhangk usingpolylacticcoglycolicacidmicrospherestoencapsulateplasmidofbonemorphogeneticprotein2polyethyleniminenanoparticlestopromoteboneformationinvitroandinvivo AT jinh usingpolylacticcoglycolicacidmicrospherestoencapsulateplasmidofbonemorphogeneticprotein2polyethyleniminenanoparticlestopromoteboneformationinvitroandinvivo AT miaol usingpolylacticcoglycolicacidmicrospherestoencapsulateplasmidofbonemorphogeneticprotein2polyethyleniminenanoparticlestopromoteboneformationinvitroandinvivo AT shic usingpolylacticcoglycolicacidmicrospherestoencapsulateplasmidofbonemorphogeneticprotein2polyethyleniminenanoparticlestopromoteboneformationinvitroandinvivo AT liux usingpolylacticcoglycolicacidmicrospherestoencapsulateplasmidofbonemorphogeneticprotein2polyethyleniminenanoparticlestopromoteboneformationinvitroandinvivo AT yuana usingpolylacticcoglycolicacidmicrospherestoencapsulateplasmidofbonemorphogeneticprotein2polyethyleniminenanoparticlestopromoteboneformationinvitroandinvivo AT liuj usingpolylacticcoglycolicacidmicrospherestoencapsulateplasmidofbonemorphogeneticprotein2polyethyleniminenanoparticlestopromoteboneformationinvitroandinvivo AT lid usingpolylacticcoglycolicacidmicrospherestoencapsulateplasmidofbonemorphogeneticprotein2polyethyleniminenanoparticlestopromoteboneformationinvitroandinvivo AT zhengc usingpolylacticcoglycolicacidmicrospherestoencapsulateplasmidofbonemorphogeneticprotein2polyethyleniminenanoparticlestopromoteboneformationinvitroandinvivo AT zhangg usingpolylacticcoglycolicacidmicrospherestoencapsulateplasmidofbonemorphogeneticprotein2polyethyleniminenanoparticlestopromoteboneformationinvitroandinvivo AT lix usingpolylacticcoglycolicacidmicrospherestoencapsulateplasmidofbonemorphogeneticprotein2polyethyleniminenanoparticlestopromoteboneformationinvitroandinvivo AT yangb usingpolylacticcoglycolicacidmicrospherestoencapsulateplasmidofbonemorphogeneticprotein2polyethyleniminenanoparticlestopromoteboneformationinvitroandinvivo AT sunh usingpolylacticcoglycolicacidmicrospherestoencapsulateplasmidofbonemorphogeneticprotein2polyethyleniminenanoparticlestopromoteboneformationinvitroandinvivo |
| _version_ |
1718403579160559616 |