Enhancing alendronate release from a novel PLGA/hydroxyapatite microspheric system for bone repairing applications.
OBJECTIVE
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.


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.
Shi
Xuetao
X
School of Materials Science & Engineering, South China University of Technology, Guangzhou, 510641, People's Republic of China.
Wang
Yingjun
Y
Ren
Li
L
Gong
Yihong
Y
Wang
Dong-An
DA
D019386:Alendronate / Q000737:chemistry / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000737:chemistry / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D017886:Durapatite / Q000737:chemistry*; D004655:Emulsions; D006801:Humans; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects; D008863:Microspheres; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology; D010012:Osteogenesis / Q000187:drug effects; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D013499:Surface Properties
D050071:Bone Density Conservation Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017886:Durapatite; D000469:Alkaline Phosphatase; D019386:Alendronate