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Enhancing alendronate release from a novel PLGA/hydroxyapatite microspheric system for bone repairing applications
Xuetao Shi1, Yingjun Wang, Li Ren
1School of Materials Science & Engineering, South China University of Technology, Guangzhou, 510641, People's Republic of China.
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.
