Free amino groups on the surface of chitosan nanoparticles and its characteristics
Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou 510120, China.Yao xue xue bao = Acta pharmaceutica Sinica 04/2007; 42(3):323-8.
The relationship of free amino groups on the surface and the characteristics of chitosan nanoparticles (CS-NPs) prepared by ionic gelation method was investigated. Free amino groups on the surface of CS-NPs were determined by colloidal titration, and the effects of the amount of free amino groups and its ionizable level on the particle size, zeta potential, appearance, drug entrapment efficiency and drug release profile in vitro of CS-NPs were investigated. The result showed that the surface free amino groups reduced, the average size, zeta potential, stability of nanoparticles, and the drug release rate and degree all decreased while the drug entrapment efficiency was not affected with the increase of tripolyphosphate (TPP) concentration. With the increase of pH, the free amino groups could be deprotonated and the ionizable level was stepped down, correspondingly the particle size and zeta potential of CS-NPs decreased. Additionally, the drug release rate and degree were elevated in acid medium while descended in neutral or base medium. The amount and ionizable level of free amino groups on the surface are affected by the gelation degree and pH, which further affected the volume phase transitions (swelling/shrinking processes) of CS-NPs. The properties of CS-NPs have correlation with the surface free amino groups.
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ABSTRACT: The aim of the present work was to investigate the potential utility of chitosan nanoparticles surface modified with glycyrrhizin (CS-NPs-GL) as new hepatocyte-targeted delivery vehicles. For this purpose, chitosan nanoparticles (CS-NPs) were prepared previously by ionic gelation process and glycyrrhizin was oxidized by sodium periodate to be conjugated to the surface of CS-NPs. The CS-NPs-GL obtained were first characterized for their morphology, particle size, zeta potential, association efficiency and in vitro release of adriamycin (ADR), using as a model drug. The nanoparticles were also labeled with rhodamine B isothiocyanate and their interaction with rat hepatocytes was examined by flow cytometry (FCM) and confocal laser microscopy (CLSM). The spherical nanoparticles prepared with oxidized GL/CS ratio of 0.14:1 (w/w) were in the 147.2nm size range, and exhibited a positive electrical charge (+9.3mV), and associated ADR quite efficiently (association efficiency: 91.7%) and showed lower extent of release (28% over 72h) in vitro. FCM and CLSM studies showed that CS-NPs-GL were preferentially accumulated in hepatocytes and the cellular uptake amount were 4.9 times more than that in hepatic nonparenchymal cells, and the uptake process was dependent on incubation time and dose of nanoparticles, which indicated that the internalization of these nanoparticles into hepatocytes was mostly mediated by a ligand-receptor interaction. In conclusion, CS-NPs-GL as a promising hepatocyte-targeted delivery carrier holds promise for further effective studies.
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ABSTRACT: Chitosan and its derivatives are extensively studied as non-viral gene delivery vectors nowadays. Polyethylene glycol-chitosan (mPEG-CS) copolymers were synthesized by oxidation of mPEG-OH and then combined mPEG-CHO with amino groups on chitosan chains. The in vitro cytotoxicity of copolymers was evaluated by MTT method. The results showed > 70% cell viability of HeLa and A549 cells after incubation with mPEG-CS copolymer from concentration 5 to 100 microg x mL(-1). The mPEG-CS copolymers with various degrees of PEG substitution were combined with DNA and the properties of mPEG-CS/DNA complexes were investigated such as nanoparticle size, zeta potential and agarose gel analysis. The best one among all these mPEG-CS copolymers was mPEG (3.55) -CS, for its capability to condense plasmid DNA was most efficient. For this reason, mPEG (3.55) -CS was picked out to mediate plasmid enhanced green fluorescence protein (pEGFP) and transfect HeLa and A549 cells. The expression of green fluorescence protein was observed by fluorescence microscope and the transfection efficiency was detected by flow cytometry. The gene expression mediated by mPEG-CS was resistant to serum, and the optimal transfection efficiency (8.1% for HeLa cells and 4.8% for A549 cells) of mPEG-CS/EGFP system was obtained under the condition of N/P 40 and 48 h transfection time. These results indicate that mPEG-CS copolymer is an efficient non-viral gene vector.
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ABSTRACT: The development of an efficient targeted drug delivery system into cells is an important subject for the advancement of drug carriers. In this study, a novel hepatocyte-targeted delivery system with glycyrrhizin (GL) surface modification based on N-caproyl chitosan (CCS) has been developed. CCS was synthesized by acylation of amino group of chitosan, and GL was oxidized to be conjugated to the surface of N-caproyl chitosan nanoparticles (CCS-NPs-GL). The synthesized nanoparticles were first characterized for their morphology, particle size, zeta potential, in vitro stability in plasma, tissue distribution, and hepatocyte-targeting uptake in vivo. The obtained results showed that the spherical and discrete nanoparticles prepared with oxidized GL/CCS ratio of 0.14:1 (w/w) exhibited a positive electrical charge and associated adriamycin quite efficiently (association efficiency: 87.5%). The prepared nanoparticles also possessed dimensional and GL surface-binding stability and slow release property in plasma in vitro. The biodistribution of these particles after intravenous injections in mice revealed accumulating drug concentrations in the liver, spleen, and lungs while decreasing drug concentrations in the heart and kidney. The content of adriamycin-loaded CCS-NPs-GL in the liver was 1.6 times higher than that of non-GL-modified CCS-NPs. Furthermore, in vivo uptake of CCS-NPs-GL by rat hepatocytes showed 2.1 times higher nanoparticle uptake compared with non-GL-modified CCS-NPs, which suggested that CCS-NPs-GL were preferentially distributed in hepatocytes by a ligand-receptor interaction. This article indicated that CCS-NPs-GL was a stable and effective drug delivery vehicle for hepatocyte targeting.
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