J Korean Med Sci.  2019 Feb;34(5):e37. 10.3346/jkms.2019.34.e37.

Alendronate-Anionic Clay Nanohybrid for Enhanced Osteogenic Proliferation and Differentiation

• Piao H
• Kim MH
• Cui M
• Choi G
• Choy JH

• KMID: 2440138
• DOI: http://doi.org/10.3346/jkms.2019.34.e37

Abstract

BACKGROUND
Alendronate (AL), a drug for inhibiting osteoclast-mediated bone-resorption, was intercalated into an inorganic drug delivery nanovehicle, layered double hydroxide (LDH), to form a new nanohybrid, AL-LDH, with 1:1 heterostructure along the crystallographic C-axis. Based on the intercalation reaction strategy, the present AL-LDH drug delivery system (DDS) was realized with an enhanced drug efficacy of AL, which was confirmed by the improved proliferation and osteogenic differentiation of osteoblast-like cells (MG63).
METHODS
The AL-LDH nanohybrid was synthesized by conventional ion-exchange reaction and characterized by powder X-ray diffraction (PXRD), high-resolution transmission electron microscopy (HR-TEM), and Fourier transform infrared (FT-IR) spectroscopy. Additionally, in vitro efficacy tests, such as cell proliferation and alkaline phosphatase (ALP) activity, were analyzed.
RESULTS
The AL was successfully intercalated into LDH via ion-exchange reaction, and thus prepared AL-LDH DDS was X-ray single phasic and chemically well defined. The accumulated AL content in MG63 cells treated with the AL-LDH DDS nanoparticles was determined to be 10.6-fold higher than that within those treated with the intact AL after incubation for 1 hour, suggesting that intercellular permeation of AL was facilitated thanks to the hybridization with drug delivery vehicle, LDH. Furthermore, both in vitro proliferation level and ALP activity of MG63 treated with the present hybrid drug, AL-LDH, were found to be much more enhanced than those treated with the intact AL. This is surely due to the fact that LDH could deliver AL drug very efficiently, although LDH itself does not show any effect on proliferation and osteogenic differentiation of MG63 cells.
CONCLUSION
The present AL-LDH could be considered as a promising DDS for improving efficacy of AL.

Keyword

Drug Delivery System; Inorganic Delivery Vehicle; Layered Double Hydroxide; Alendronate; Osteogenic Proliferation and Differentiation; Drug-Clay Nanohybrid

MeSH Terms

Alendronate
Alkaline Phosphatase
Cell Proliferation
Drug Delivery Systems
Fourier Analysis
In Vitro Techniques
Microscopy, Electron, Transmission
Nanoparticles
Spectrum Analysis
X-Ray Diffraction
Alendronate
Alkaline Phosphatase