The development of liposome encapsulated calcium phosphates for bone regeneration
- Publication Type:
- Thesis
- Issue Date:
- 2010
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Osteoporosis, a degenerative bone disorder, is one of the leading causes of morbidity in the
elderly. Proper nutrition plays a role in the prevention and treatment of osteoporosis. Intake
of calcium and Vitamin D are some of the most important nutritional factors, and
supplementation remains the gold standard and first line of treatment for low bone mineral
density and osteoporosis. Supplementation can prevent bone loss and reduce fracture risk.
This work set about to produce, characterise and encapsulate for direct delivery to the bone
various micro and nano sized calcium based mineral compounds which may be beneficial to
bone health, using the precipitation method and biomimetic processes.
Calcium phosphate mineral was produced and characterised, including hydroxyapatite (Hap),
dicalcium phosphate dihydrate (DCPD), as well as multiphase and substituted calcium
phosphates using biomimetic process. Standard simulated body Fluid (SBF) solution was
modified, creating a high carbonate solution which better mimics the bone environment, and
produces precipitates more similar to bone than traditional low carbonate SBF, as confirmed
using Fourier Tansform Infrared Spectroscopy (FTIR) and X-Ray Diffraction (XRD).
The use of liposomes as a delivery vesicle for the calcium mineral was evaluated usmg
FTIR, XRD, Electron Dispersive Spectroscopy, Mass Spectrometry Transmission and
Scanning Electron Microscopy, and X-Ray Mapping. The calcium mineral from aqueous
solutions and prepared HAp and DCPD was incorporated into the liposome.
Functional groups were synthesised based on a published structure used to target the bone
marrow macrophage, and incorporation into liposomes was confitmed using Nuclear
Magnetic Resonance Spectroscopy and FTIR. Preliminary cell culture studies showed no
direct effect on osteoblast like Mg63 or Saos-2 cells or osteoclast resorption, measured by
bone collagen release.
Macrophage response was explored using U93 7 cell line. Expression of TNF-a and IL-1 ,
markers of inflammation, increased with liposome treatments compared to the negative control
but decreased compared the positive control. The Mg63 cells given U937 supematants showed
liposomes increased OPG production, but this was regardless of mineralisation.
The calcium based mineral compounds were produced, characterised, successfully
encapsulated using liposomes and functionalised to improve uptake at the bone site . This
shows the potential to deliver calcium to the bone, however further work to inhibit
inflammation and increase the calcium dose to elicit greater cell response is required before
this approach can be developed as a treatment option.
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