| Chitosan (CS)-stearic acid (SA) conjugates (CS-SA) are prepared with stearicacid as the hydrophobic groups. The CS-SA nanoparticles are prepared by probesonication in aqueous media, and used as biodegradable carriers of conjugated linoleicacid (CLA) that can confer sustained oral release of CLA in addition to enhancing itsoverall dissolution and oral bioavailability. The CLA-loaded CS-SA nanoparticles areencapsulated into alginate microparticles for the preparation of nano/micro hybridparticles, which can improve the stability of CS-SA nanoparticles and the oralsustained release of silymarin.CS-SA conjugates with different degree of amino substitution (DS) issynthesized by EDC-mediated coupling reaction. CS-SA conjugates werecharacterized by1H NMR. The DS of CS-SA, as elemental analysis determined, is13.34,18.02, or21.36SA groups per hundred sugar residues of chitosan.The critical aggregation concentrations (CAC) of CS-SA nanoparticles aredetermined by fluorescence measurement using pyrene as a probe, which are0.037,0.031,0.027mg/ml, respectively. The CAC decreases with the increasing of DS. Theparticle size and zeta potential of CS-SA nanoparticles are measured by dynamic lightscattering (DLS) and a Zetasizer. With the increase of DS of CS-SA, the size and thezeta potential of CS-SA nanoparticles decrease. The average sizes of CS-SAnanoparticles are265.7,238.8,219.0nm. The zeta potentials of CS-SA nanoparticlesare27.8,25.5,23.6mV. The transmission electron micrograph of the nanoparticlesshows that they are spherical in shape.CLA is selected as a model nutrient to prepare CLA-loaded CS-SA nanoparticles.After encapsulating CLA, the size of CS-SA nanoparticles increases, while the zetapotential decreases. The CLA entrapment efficiency and in vitro drug release behaviorof CS-SA nanoparticles are investigated. With the increase of the feed weight ratio ofCLA to CS-SA conjugates, the encapsulation efficiency reduces, and the nutrient loading content increases. On the other hand, with the increase of DS of CS-SA, theencapsulation efficiency and nutrient loading content of CS-SA nanoparticles increase.The maximum loading content of CS-SA nanoparticles is10.77%. The nutrient israpidly released from the CS-SA nanoparticles in simulated gastric fluid due to therapid dissociation and degradation of CS-SA nanoparticles at low pH values.81.76%of the initial nutrient loading is found to be released in the duration of3h.A novel formulation of nano/micro hybrid particles is developed for thesustained release of CLA. Droplet generator is used for producing hybrid particles.The optical micrograph of the hybrid particles shows that they are spherical in shape.With the increase of the feed weight ratio of CS-SA nanoparticles to sodium alginate,the size of the hybrid particles increases. The average size of the hybrid particles is inthe range of130.208to164.965μm. The fluorescent image shows that the CS-SAnanoparticles lie within the matrix. The CLA-loading and release behavior of thehybrid particles are investigated. With increasing the percent of CLA-loaded CS-SAnanoparticles, the encapsulation efficiency and nutrient loading content of the hybridparticles increase. A lower release of CLA from the hybrid particles is observed insimulated gastric fluid, in which the minimum release is only14.65%in3h. After this,CLA is released in a continuous way in simulated intestinal fluid.The nano/micro hybrid particles are characterized using FTIR and SEM.Swelling characteristics at different pH values are investigated. The cytotoxicity ofhybrid particles is analyzed by the MTT assay. Furthermore, based on the drug releaseresults, the release mechanisms are analyzed and discussed. The FTIR spectra of thehybrid particles indicate that intermolecular hydrogen bands may exist in the hybridparticles. Compared with the SEM image of alginate microparticles, the hybridparticles have, in general, more spherical shapes and their surface is smoother.Increasing the percentage of CS-SA nanoparticles relative to that of alginate tends, ingeneral to increase the swelling values of the hybrid particles attained at equilibriumin both pH1.2and pH7.4. The hybrid particles attain relatively higher swelling valuesat equilibrium in pH7.4as compared to that in pH1.2. There are two different phasesof release mechanisms in the hybrid particles, namely diffusional transport within the first2h and anomalous transport during2~7h. The hybrid particles exhibit nocytotoxicity for Caco-2cells at the concentration range from50to500μg/ml. |
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