Preparation, characterization and biodistribution of ultrafine chitosan nanoparticles.

Chitosan nanoparticles cross-linked with glutaraldehyde have been prepared in AOT/n hexane reverse micellar system. The cross-linking in the polymeric network has been confirmed from FTIR data. Because of the adhesive nature of these particles, their sizes, as measured by QELS, have been found dependent on the particle density in aqueous buffer. The particle size has also been found to vary with the amount of cross-linking. The actual particle size of these chitosan nanoparticles with a particular degree of cross-linking has been determined at infinite dilution of particles in water. The particle size at infinite dilution is approximately 30 nm diameter, when 10% of the amine groups in the polymeric chains have been cross-linked and it shoots up to 110 nm diameter when all the amine groups are cross-linked (100% cross-linked). TEM pictures show that these particles are spherical in shape and remain in the form of aggregation. The biodistribution of these particles after intravenous injections in mice showed that these particles readily evade the RES system and remain in the blood for a considerable amount of time. The gamma image of the rabbit after administration of (99m)Technetium (99mTc) tagged chitosan nanoparticles also confirms the above observation, as the blood pool is readily visible even after 2 h. The gamma picture shows distribution of particles in the heart, liver, kidneys, bladder and the vertebral column. Interestingly, the biodistribution studies of the chitosan nanoparticles have indicated that these particles are distributed in the bone marrow also, implying the possibility of using these nanoparticles for bone imaging and targeting purpose. Copyright 2002 Elsevier Science B.V.