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Enhancing Alendronate Release from a Novel PLGA/Hydroxyapatite Microspheric System for Bone Repairing Applications

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Abstract

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.

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Acknowledgements

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.

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Authors and Affiliations

  1. School of Materials Science & Engineering, South China University of Technology, Guangzhou, 510641, People’s Republic of China

    Xuetao Shi, Yingjun Wang & Li Ren

  2. Division of Bioengineering, School of Chemical & Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, N1.3-B2-13, Singapore, 637457, Republic of Singapore

    Xuetao Shi, Yihong Gong & Dong-An Wang

  3. Key Laboratory of Specially Functional Materials and Advanced Manufacturing Technology, South China University of Technology, Ministry of Education, Guangzhou, 510641, People’s Republic of China

    Xuetao Shi, Yingjun Wang & Li Ren

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  1. Xuetao Shi
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Correspondence to Dong-An Wang.

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Shi, X., Wang, Y., Ren, L. et al. Enhancing Alendronate Release from a Novel PLGA/Hydroxyapatite Microspheric System for Bone Repairing Applications. Pharm Res 26, 422–430 (2009). https://doi.org/10.1007/s11095-008-9759-0

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