Yolk @ cage-Shell Hollow Mesoporous Monodispersion Nanospheres of Amorphous Calcium Phosphate for Drug Delivery with High Loading Capacity
Huang et al. Nanoscale Research Letters (2017) 12:275
DOI 10.1186/s11671-017-2051-7
NANO EXPRESS
Open Access
Yolk @ cage-Shell Hollow Mesoporous
Monodispersion Nanospheres of
Amorphous Calcium Phosphate for Drug
Delivery with High Loading Capacity
Suping Huang1*, Chunxia Li1 and Qi Xiao2
Abstract
In this paper, yolk-shell hollow nanospheres of amorphous calcium phosphate (ACP) are prepared, and its loading
capacity is investigated by comparing with that of solid-shell hollow structure ACP and cage-shell hollow structure
ACP. Results show that the products are yolk @ cage-shell of ACP with large shell’s pores size (15-40 nm) and large
cavity volume. Adsorption results show that the loading capacity of yolk @ cage-shell hollow spherical ACP is very
high, which is more than twice that of hollow ACP and 1.5 times of cage-like ACP. The main reasons are that the big
shell’s pore size contributes the large molecular doxorubicin hydrochloride (DOX · HCl) to enter the inner of hollow
spheres easier, and the yolk-shell structure provides larger interior space and more adsorption sites for loading drugs.
Keywords: Amorphous calcium phosphate, Yolk @ cage-shell hollow nanospheres, DOX · HCl, Loading capacity
Background
Over the past decades, many efforts have been devoted
to design novel controlled drug-delivery systems, which
are superior to commercial administrated drugs in terms
of dosage, due to their high delivery efficiency [1], low
side effects [2], and low toxicity [3]. To date, various
polymer [4], inorganic [5], and inorganic/organic hybrid
materials [6] with diverse structures and shapes have
been employed as vehicles for drug delivery. Particularly,
calcium phosphate salts have gained considerable attention
in the delivery of different drugs due to their excellent
biocompatibility, low toxicity, excellent nonimmunogenicity
and osteoconductive properties [7–10]. However, the relatively low surface area and small pore volume may limit
their application. Thus, developing a kind of functional hollow calcium phosphate spheres should be highly potential,
not only due to their biomedical characteristics but for their
large interior space and tunable porous shell, which is
suitable for loading more drugs and diffusing the drug
molecules through the channels freely.
* Correspondence:
1
State Key Lab of Powder Metallurgy, Central South University, Changsha
410083, Hunan, China
Full list of author information is available at the end of the article
In order to enhance the loading capacity, various
calcium phosphate materials with diverse morphologies
and size have been prepared [11–14], such as calcium phosphate composite nanoparticles [15, 16], hydroxyapatite
hollow microspheres [17–19], hydroxyapatite microtubes
[20, 21], hydroxyapatite assembled hollow fibers [22], hydroxyapatite nanowires [23], and flower-like hierarchically
nanostructured hydroxyapatite hollow spheres [24]. Among
the different morphological nanostructures, yolk-shell
hollow spheres with porosity [25] are more advantageous
for applications in biomedical fields such as loading drug,
protein or DNA molecules, due to their different specific
surface areas and morphologies [26, 27]. However, the
reports about yolk-shell calcium phosphate particles are
very little, and the particles reported previously could not
meet the loading requires because their big yolk size compared with the shell, which results in the smaller interior
space and low loading capacity [25].
On the other hand, the shell’s pore sizes of hollow
sphere nanoparticles are very important for the delivery
of drugs into cells. Large molecular/volume drugs are
difficult to enter the small shell’s pores, and mostly
adsorb on the surface of hollow spheres. It is a challenge
to synthesize yolk-shell hollow structures of ACP with
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
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Huang et al. Nanoscale Research Letters (2017) 12:275
small particle sizes but simultaneously bigger pore
sizes and larger interior space for the delivery of large
molecular weight therapeutics.
In this paper, we will prepare a kind of yolk-shell
hollow mesoporous nanospheres of calcium phosphate
with bigger pore sizes and large interior space, and
compare the loading capacity of yolk-shell structure
with the solid-shell hollow structure and cage-like hollow
structure. At the same time, the effect of yolk-shell structure’s pore sizes and cavity volume on the loading capacity
will be investigated.
Methods
Materials
All chemicals used throughout the experiments were of
analytical grade and without further purification. Calcium
nitrate [Ca(NO3)2 · 4H2O, 99 wt%] as a source of Ca was
purchased from Tianjin Hengxing Chemical Co., Ltd.,
China. Phosphorus pentoxide (P2O5, 98 wt%) as a
source of P was purchased from Tianjin Kermel Chemical
Reagent Co., Ltd., China, and an ammonia solution
(NH3·H2O, 25–28 wt%) was purchased from Zhuzhou
Quartzification Glass Co., Ltd., China. Anhydrous ethanol
(CH3CH2OH, 99.7 wt%) was purchased from Tianjin
Zhiyuan Chemical Reagent Co., Ltd., China.
Page 2 of 7
5 min), followed by drying at 50 °C for at least 24 h. Finally,
the dried powder was calcinated up to 500 °C under air
atmosphere with heating rate 2 °C/min and 10 °C/min
(named ACP-24-2, ACP-48-2 and ACP-48-10, respectively, the number denotes the process parameter). In
the process of calcination, the temperature was to keep
heat-preservation at 100, 250, 500 °C for 1, 1, and 4 h
respectively.
Drug Loading
DOX · HCI was dissolved in deionized water to a concentration of 10 mg mL−1. Twenty milligrams of ACP
nanoparticles was dispersed in 10 mL of the DOX solution. The mixture was stirred at room temperature for
24 h. Then, the DOX · HCI concentration of the supernatant was measured by UV-visible spectrophotometry at
480 nm. Then, the loading capacity was calculated by the
equation as follows:
Q ¼ ðC 0 −C Þ V =m
In the equation, Q (in mg g−1) is the amount of
DOX · HCl adsorbed; C0 and C (in mg mL−1) are the
concentrations of the solution containing of DOX before
and after adsorption, respectively; V (in mL) is the volume
of the solution; and m (in g) is the amount of ACPs.
Synthesis of Phenol-Formaldehyde Resin Spheres (PRs)
Monodisperse phenol-formaldehyde resin spheres (PRs)
were synthesized by using resorcinol and formaldehyde
solution as precursors. Generally, ammonia aqueous
solution (NH4OH, 25 wt%, 0.1~0.3 mL) was mixed with
a solution containing absolute ethanol (EtOH, 0~28 mL)
and deionized water (H2O, 0~28 mL) (with totally amount
of 28 mL) to prepare PRs with different sizes. After stirring for more (...truncated)
