Synthesis and characterization of chitosan–poly(acrylic acid) nanoparticles
Introduction
Recently, polymer nanoparticles have been widely investigated as a carrier for drug delivery [1], [2], [3]. Among them, much attention has been paid to the nanoparticles made of synthetic biodegradable polymers such as poly-ε-caprolactone (PCL) [4], [5], polylactide (PLA) [6], and their copolymers [7], [8], [9] due to their good biocompatibility, biodegradability, and novel drug release behavior. However, these nanoparticles are not ideal carriers for hydrophilic drugs like peptides, protein and some anticancer drugs because of their strong hydrophobic property. To improve their hydrophilic property, many different hydrophilic nanoparticles have been developed as hydrophilic drug carriers. Among those hydrophilic systems, poly(ethylene glycol) (PEG) modified polyester nanoparticles are the promising carriers for the hydrophilic drugs due to the hydrophilic property and other outstanding physico-chemical and biological properties of PEG [10], [11], [12]. But these hydrophobic–hydrophilic nanoparticles have a limitation in their preparation procedure, which requires the use of organic solvents and surfactants as well as sonication or homogenization.
Chitosan, a kind of nature polysaccharide, having structural characteristics similar to glycosaminoglycans, is non-toxic and biodegradable [13], which has rendered it widely, applicable in the pharmaceutical and biomedical fields [14], [15], [16]. In the recent years, chitosan microspheres and beads have been investigated as drug delivery systems for anticancer drug or protein [17], [18], [19]. Many approaches have been developed to prepare the chitosan beads including water in oil method [20], [21], emulsion-droplet coalescence technique [22] and spray drying process [23]. Usually, these preparation procedures are complex and need to use some organic solvents or surfactants. In addition, by these techniques, the beads are not appropriate for the routes of administration; For example, vein injection due to their large size (larger than 2 μm) [20], [21], [23].
To overcome these drawbacks, many works have been done. Leong et al. [24] reported CS-DNA nanoparticles prepared by coacervation of CS and DNA in acidic solution. The size of the CS-DNA nanoparticles was in the range of 100–250 nm, and such nanoparticles can protect the encapsulated plasmid DNA from nuclease degradation. Alonso et al. [25] developed a kind of hydrophilic chitosan–polyethylene oxide nanoparticles prepared by the ionic interaction between positively charged CS and negatively charged polymer-tripolyphosphate (TPP), and the nanoparticles showed a great protein loading capacity and sustained release ability.
In the present work, we report a new approach to prepare hydrophilic nanoparticles based on polymerizing acrylic acid into chitosan template in aqueous solution [26]. We think that this system has some interesting features: (1) The nanoparticles are obtained spontaneously under very mild conditions without the need of high temperature, organic solvent, surfactant and some other special experimental technology; (2) the nanoparticles have small particle size and positive surface charges, which may improve their stability in the presence of biological cations [27], and is favorable for some drugs due to the interaction with negatively charged biological membranes and site-specific targeting in vivo [28], [29]; (3) The nanoparticles have pH-dependent dissolution behavior.
Section snippets
Materials
Chitosan (Nantong Shuanglin Biological Product Inc.) was refined twice by dissolving it in dilute acetic acid solution, filtered, precipitated with aqueous NaOH, and finally dried in vacuum at room temperature. The degree of deacetylation was about 90%, and the weight average molecular weights of chitosan were 40, 80, 100, 200 and 300 kDa, respectively, determined by viscometric methods [30]. Potassium persulfate (K2S2O8) was recrystallized from distilled water. Acrylic acid (AA) (Shanghai
Synthesis of CS–PAA nanoparticles
The CS–PAA nanoparticles were prepared by two methods in our study. One was polymerization of AA in CS solution. Another is mixture of positively charged CS and negatively charged PAA with dropping method. The polymerization of acrylic acid in the presence of chitosan is showed in Scheme 1. First, CS was dissolved in AA solution, and then the polymerization of AA was initiated by K2S2O8. When the polymerization of AA reached a certain level, the inter- and intra-molecular linkages occurred
Conclusion
The CS–PAA nanoparticles can be prepared by polymerizing acrylic acid into chitosan template. The remarkable advantage of this system is that it is solely made of hydrophilic polymers: chitosan and poly(acrylic acid), which are non-toxic, and biodegradable. All these CS–PAA nanoparticles are obtained under mild conditions without any organic solvents and surfactants. These nanoparticles are stable under acidic and neutral conditions ranging from 4 to 8, and aggregate at pH>9. Furthermore,
Acknowledgements
The authors are thankful to Natural Science Foundation of Jiangsu Province, China for the partial financial support of this study.
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