TY - JOUR
T1 - Enhancing alendronate release from a novel PLGA/hydroxyapatite microspheric system for bone repairing applications
AU - Shi, Xuetao
AU - Wang, Yingjun
AU - Ren, Li
AU - Gong, Yihong
AU - Wang, Dong An
N1 - Funding Information:
This research was supported by China Scholarship Council (2007U33046), and the National Natural Science Foundation of China (Grant 50572029), the Key Programs of the Ministry of Education (Grant 305012), the Key Projects in the National Science & Technology Pillar Program in the Eleventh Five-year Plan Period (Grant 2006BA116B04), the State Key Program of National Natural Science of China (Grant 50732003), and also supported by Grant ARC 10/06, Ministry of Education, Singapore.
PY - 2009/2
Y1 - 2009/2
N2 - Purpose. The goal of this study was to exploit the multifunction of PLGA based microsphere as efficient alendronate delivery and also as potential injectable cell carrier for bone-repairing therapeutics. Materials and Methods. Novel poly (lactic-co-glycolic acid) (PLGA)-hybridizing -hydroxyapatite (HA) microspheres loaded with bisphosphonate-based osteoporosis preventing drugs, alendronate (AL), are prepared with solid/oil/water (s/o/w) or water/oil/water (w/o/w) technique. Macrophage resistance was evaluated by MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, DNA assay and Live/dead staining, and osteoblast proliferation and maturation was assessed by MTT assay, Alkaline phosphatase (ALP) activity assay and Real time-PCR. Results. In such fabricated AL laden PLGA/HA microspheric composites (abbreviated "PLGA/HA-AL"), the introduction of HA component has been proven capable of largely enhancing drug encapsulation efficiency especially when the single emulsion protocol is adopted. The in-vitro drug (AL) releasing profile of PLGA/HA-AL system was plotted basing over 30 days' data collection. It indicates a sustained releasing tendency despite a minimal burst at the very beginning. The in-vitro bone-repairing efficacy of PLGA/HA-AL system was first tested with macrophages that are identified as precursors of osteoclasts and potentially responsible for osteoporosis. The results indicated that the AL release significantly inhibited the growth of macrophages. Additionally, as a central executor for osteogenesis, osteoblasts were also treated with PLGA/HA-AL system in vitro. The outcomes confirmed that this controlled release system functions to improve osteoblast proliferation and also enables upregulation of a key osteogenic enzyme ALP. Conclusions. By pre-resisting osteoclastic commitment and promoting osteoblastic development in vitro, this newly designed PLGA/HA-AL controlled release system is promoting for bone-repairing therapeutics.
AB - Purpose. The goal of this study was to exploit the multifunction of PLGA based microsphere as efficient alendronate delivery and also as potential injectable cell carrier for bone-repairing therapeutics. Materials and Methods. Novel poly (lactic-co-glycolic acid) (PLGA)-hybridizing -hydroxyapatite (HA) microspheres loaded with bisphosphonate-based osteoporosis preventing drugs, alendronate (AL), are prepared with solid/oil/water (s/o/w) or water/oil/water (w/o/w) technique. Macrophage resistance was evaluated by MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, DNA assay and Live/dead staining, and osteoblast proliferation and maturation was assessed by MTT assay, Alkaline phosphatase (ALP) activity assay and Real time-PCR. Results. In such fabricated AL laden PLGA/HA microspheric composites (abbreviated "PLGA/HA-AL"), the introduction of HA component has been proven capable of largely enhancing drug encapsulation efficiency especially when the single emulsion protocol is adopted. The in-vitro drug (AL) releasing profile of PLGA/HA-AL system was plotted basing over 30 days' data collection. It indicates a sustained releasing tendency despite a minimal burst at the very beginning. The in-vitro bone-repairing efficacy of PLGA/HA-AL system was first tested with macrophages that are identified as precursors of osteoclasts and potentially responsible for osteoporosis. The results indicated that the AL release significantly inhibited the growth of macrophages. Additionally, as a central executor for osteogenesis, osteoblasts were also treated with PLGA/HA-AL system in vitro. The outcomes confirmed that this controlled release system functions to improve osteoblast proliferation and also enables upregulation of a key osteogenic enzyme ALP. Conclusions. By pre-resisting osteoclastic commitment and promoting osteoblastic development in vitro, this newly designed PLGA/HA-AL controlled release system is promoting for bone-repairing therapeutics.
KW - Alendronate
KW - Bone repair
KW - Drug delivery
KW - Hydroxyapatite
KW - Microspheres
KW - PLGA
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U2 - 10.1007/s11095-008-9759-0
DO - 10.1007/s11095-008-9759-0
M3 - Article
C2 - 18979188
AN - SCOPUS:58549091279
SN - 0724-8741
VL - 26
SP - 422
EP - 430
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 2
ER -