Designing a trifunctional hydroxyapatite based nanocapsule with bone targeting properties

• Main Author: Cho, Xing Ling.
• Other Authors: Loo Say Chye Joachim
• Format: Final Year Project
• Language: English
• Published: 2011
• Subjects: DRNTU::Engineering
• Online Access: http://hdl.handle.net/10356/44558
• Institution: Nanyang Technological University

Hydroxyapatite (HA) and Bisphosphonate (BP) are well known for their close resemblances to natural bone and have been widely used in medical treatments for bone deprivation diseases for many years. As such, a hybrid model encompassing the qualities of both HA and BP would serve as a promising tool for effective drug delivery with specific bone targeting. In this project, a new methodological approach via surface silanisation chemistry was proposed to construct such hybrid material. HA nanocapsules were first fabricated using Sodium Dodecyl Sulfate (SDS) micelles as a template to synthesise nanoparticles with hollow cores. The surfaces of the nanocapsules were then chemically treated with a silane agent, embedded with Polyethylene-glycol (PEG) and an N-Hydroxysuccinimide (NHS) ester end group. The presence of NHS esters would enhance further coupling of BP moieties whereas the formation of PEG layer would conceal the native hydroxyl groups of HA to minimise any undesired non-specific cellular uptake. BP moieties were then grafted onto the surfaces of the silane functionalised HA nanocapsules via carbodiimide mechanism. Surface characterisations of these nanocapsules were analysed using FTIR, FESEM, TEM, XRD, XPS and DLS. To further validate its bone targeting potentials, pig bone surfaces were incubated with these BP-tagged HA nanocapsules. FESEM analysis of the bone slides had evidently proven that these modified nanocapsules would bind strongly to bone surfaces compared to the unmodified HA nanocapsules. We predict that the synergy of individual virtues between HA and BP would render the proposed construct a trifunctional attribute; 1) HA would assist in recovery of bone bioactivity, 2) BPs would aid in the arrestment of further bone deprivation and 3) the potential of drug encapsulation within the hollow core of the nanocapsule.