Calcium phosphate/block copolymer hybrid porous nanospheres: Preparation and application in drug delivery
Introduction
As the principal inorganic component of bones and teeth, calcium phosphate (CaP) is considered as an ideal biomaterial for various biomedical applications due to its excellent biocompatibility and biodegradability [1], [2]. In the past few years, CaP nanomaterials have attracted a great deal of attention in the field of biomedicine. Recently, uniform and well-dispersed CaP nanoparticles were synthesized under the concept of van der Waals chromatography (vdW-HPLC laundering), and these CaP nanoparticles performed well in the application of in vitro imaging and drug delivery after binding with various kinds of organic molecules [3], [4], [5]. Polymer-functionalized CaP nanoparticles were also prepared and they were used as efficient carriers for photodynamic therapy [6].
CaP hollow nanostructures are considered to be advantageous because of their large specific surface area and high capacity for loading drug, protein or DNA molecules. Several methods have been employed to prepare CaP hollow nanostructures, for example, polyelectrolyte-mediated mineralization [7], [8], template approaches [9], [10], [11], ultrasonic-assisted route [12], etc. However, there have been few fabrication methods reported for CaP porous nanostructures. To satisfy the increasing demand of biomedical applications, it is essential to develop facile ways for the synthesis of CaP porous nanostructures.
Herein, we report a facile room-temperature solution method for the synthesis of calcium phosphate (CaP)/block copolymer hybrid porous nanospheres using CaCl2 and (NH4)2HPO4 in the presence of a block copolymer. The as-prepared CaP/PLLA-mPEG hybrid porous nanospheres were explored as drug carriers, and showed high ibuprofen loading capacity and in vitro prolonged drug release behavior in a simulated body fluid.
Section snippets
Experimental section
The block copolymers used in this work were poly(dl-lactide-co-glycolide)-block-monomethoxy(polyethyleneglycol) (PLGA-mPEG), poly(l-lactide)-block-monomethoxy(polyethyleneglycol) (PLLA-mPEG), and poly(l-lactide)-block-polyethyleneglycol-block-poly(l-lactide) (PLLA-PEG-PLLA), and they were synthesized according to a method reported in the previous publication [13]. For PLGA-mPEG, the molecular weight of the PEG segment was 2000, and the molar ratio of lactide to glycolide repeat units LA/GA was
Results and discussion
Fig. 1 displays the morphologies of the samples investigated with transmission electron microscopy (TEM, JEOL JEM-2100F). As shown in Fig. 1(a)–(c), porous nanospheres were formed in the presence of any of three PEG-based block copolymers. The average diameter of the porous nanospheres was less than 100 nm for all three samples. By contrast, if PEG was used instead of the block copolymer, only irregular nanoparticles were obtained, as shown in Fig. 1(d).
To investigate the composition of the
Conclusions
In summary, the calcium phosphate (CaP)/block copolymer hybrid porous nanospheres were synthesized by a simple solution method using CaCl2 and (NH4)2HPO4 in the presence of a block copolymer at room temperature. X-ray diffraction showed that calcium phosphate in the hybrid porous nanospheres was amorphous (ACP). The as-prepared CaP/PLLA-mPEG hybrid porous nanospheres were explored as drug carriers, and showed high ibuprofen loading capacity and in vitro prolonged drug release behavior in a
Acknowledgments
This work was financially supported by the Science and Technology Commission of Shanghai (1052 nm06200, 0852 nm05800), the National Natural Science Foundation of China (50772124, 50821004), and the Shanghai-Unilever Research and Development Fund (09520715200). We thank Professor Yourong Duan from the Cancer Institute of Shanghai Jiao Tong University for her kind provision of the block copolymers.
References (18)
- et al.
J. Mater. Chem.
(2010) Chem. Rev.
(2008)- et al.
Nano Lett.
(2009) - et al.
Nano Lett.
(2008) - et al.
Nano Lett.
(2008) - et al.
Biomaterials
(2009) - et al.
Angew. Chem. Int. Ed.
(2002) - et al.
Colloid Poly Sci
(2002) - et al.
J. Mater. Chem.
(2008)
Cited by (25)
(NaPO<inf>3</inf>)<inf>6</inf>-assisted formation of dispersive casein-amorphous calcium phosphate nanoparticles: An excellent platform for curcumin delivery
2020, Journal of Drug Delivery Science and TechnologyTargeted polymeric therapeutic nanoparticles: Design and interactions with hepatocellular carcinoma
2015, BiomaterialsCitation Excerpt :A t-test was used to detect differences between groups, and p < 0.05 was considered statistically significant in all evaluations. We synthesized three polymers, PDLA-CS (Supplementary Fig. 1) [13–15], PEG-PLGA-PLL (Supplementary Fig. 2) [6–8], and PEG-PS (Supplementary Fig. 3) [9–12]. Each of these polymers has hydrophilic and hydrophobic chains that allow them to easily self-assemble to form NPs.
Selective binding and magnetic separation of histidine-tagged proteins using Ni<sup>2+</sup>-decorated Fe<inf>3</inf>O<inf>4</inf>/hydroxyapatite composite nanoparticles
2014, Materials LettersCitation Excerpt :These approaches, although promising, are often limited by complicated synthesis routes and time-consuming experiment techniques. Due to its favorable biocompatibility and adsorption capacity, HAP NPs have been studied for drug delivery, tissue engineering and protein adsorption [15,16]. Especially, HAP has rich surface active sites, and can immobilize metal ions through chelating bond.
Naturally and synthetic smart composite biomaterials for tissue regeneration
2013, Advanced Drug Delivery ReviewsCitation Excerpt :When the proteins were encapsulated within the inner PLGA part the release rate was further reduced. A delivery system of drugs within the CaP microspheres was also developed, where alendronate was in-situ loaded [163]. A sustainable release pattern of drug over 40 days was evident, and the release rate was controllable by modulation of the proportion of amorphous phase and the consequent degradation rate.
Peptide decorated calcium phosphate/carboxymethyl chitosan hybrid nanoparticles with improved drug delivery efficiency
2013, International Journal of PharmaceuticsCitation Excerpt :For example, poly(ethylene glycol)-b-poly(aspartic acid) was used to control the crystallization of Ca–P and form a hybrid vector with improved gene transfection efficiency (Kakizawa et al., 2004). Tri-block and di-block copolymers containing poly(ethylene glycol) and polylactide segments could form hybrid nanoparticles with Ca–P with various sizes (Wang et al., 2010a,b). Carboxylmethyl cellulose was utilized to form hybrid particles with CaCO3 with controllable sizes (Peng et al., 2010; Zhao et al., 2007).