Colloids and Surfaces B: Biointerfaces 85 (2011) 221–228
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Colloids and Surfaces B: Biointerfaces
journal homepage: www.elsevier.com/locate/colsurfb
Development and evaluation of cyclodextrin complexed hydroxyapatite
nanoparticles for preferential albumin adsorption
Sunita Prem Victor, Chandra P. Sharma
∗
Division of Biosurface technology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Science and Technology, Poojappura, Thiruvananthapuram 695012,
Kerala, India
article info
Article history:
Received 23 November 2010
Received in revised form 23 February 2011
Accepted 23 February 2011
Available online 16 March 2011
Keywords:
Hydroxyapatite
-Cyclodextrin
Protein adsorption
Blood compatibility
abstract
Our study focuses on the incorporation of -CD into the HA structure, its effects on the phase of HA and the
biological responses to proteins and blood cells. Hydroxyapatite (HA) containing levels of -cyclodextrin
(-CD) of upto 0.9 wt% has been produced by co-precipitation method. The complexes were analyzed
by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR)
spectroscopy, thermal gravimetric analysis (TG) and differential scanning analysis (DSC) methods. The
size of the complexes as analyzed using DLS (dynamic light scattering) was between 150 nm and 350 nm.
The results show that an increase in concentration of -CD in the prepared samples that leads to an
increase in hydrophobicity seems to promote an affinity for albumin adsorption. The PAGE results were
substantiated by Lowry measurements and the results reveal that the H2 (containing 0.7 wt% -CD)
sample shows around 40% increase in albumin adsorption when compared to the H1 (containing 0.5 wt%
-CD) sample. The preferential adsorption of albumin has not been demonstrated in vivo. The ability
to design particles that can preferentially interact with particular protein can obtain desired targeting
effects. So the results indicate that HA/-CD complexes have immense potential in targeted delivery of
drugs. The in vivo potential of the developed samples was further confirmed in vitro by the results of cell
aggregation and haemolytic activity.
© 2011 Elsevier B.V. All rights reserved.
1. 1 Introduction
Hydroxyapatite (Ca
10
(PO
4
)
6
(OH)
2
, HA) is one of the most exten-
sively employed calcium phosphates owing to its similarity to the
main mineral constituent of bone tissue [1]. The substitution and
incorporation of ions affect various properties of apatite including
crystalline size. The hydroxyl ions in the HA crystal play an impor-
tant role in ion exchange, ionic conductance, solubility and surface
modification [2]. The excellent biological properties of HA, such as
the lack of toxicity, inflammatory responses, and high bio resorba-
bility can be significantly increased by lowering their crystallinity
[3]. The dissolution rate of HA has also been found to be affected
by changes in crystallinity and crystalline size [4]. So it is advan-
tageous to prepare HA with properties such as low crystallinity,
crystalline disorder and the presence of carbonate ions in the lattice
[5]. Various methods have been employed to bring about changes in
properties of the synthesised HA particles [6–8]. A recent study also
reported the structural and biological effects of the incorporation
of titanium into the HA lattice [9].
∗
Corresponding author. Tel.: +91 4712520214/264; fax: +91 471 2341814.
E-mail address: sharmacp@sctimst.ac.in (C.P. Sharma).
-Cyclodextrin, a macrocyclic oligosaccharides contains seven
-(1,4) linked glycosyl unit and has a unique molecular structure
that makes them sparingly water soluble but suitable candidates
to accommodate hydrophobic moieties/molecules in the cavity.
They can be visualised as hollow truncated cones with hydrophilic
rims on the exterior with an interior hydrophobic cavity [10].
This special molecular arrangement makes them ideal candidates
for drug delivery and for stabilisation of proteins against aggre-
gation, thermal denaturing and degradation [11]. They thus find
numerous applications such as chiral chromatographic separa-
tions, solubilization of lipophilic compounds, improvement of drug
bioavailability, increasing the shelf life of therapeutic proteins,
enzyme mimicking and drug delivery [12,13].
HA possesses two different binding sites, the C and the P sites
respectively on its surface and this provide proteins a multiple site
binding opportunity [14]. The C sites are rich in calcium ions or
positive charge and thus bind to acidic groups of proteins, but the
P sites lack calcium ions or positive charge and therefore attach to
basic groups of proteins. Specific recognition of proteins is a major
ambition in the application of nanoparticles in the biological field.
The specificity of nanoparticles- protein interactions is essential in
a wide variety of processes including biodistribution, cell adhesion,
inflammation and compatibility [15]. Proteins bind the surface of
nanoparticles as soon as they are introduced into a physiological
0927-7765/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.colsurfb.2011.02.032