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Drug delivery with polybutylcyanoacrylate nanoparticles to the retina, brain and main organs of rats
Because the blood-brain barrier (BBB) is an obstacle for drug-delivery, carrier systems such as polybutylcyanoacrylate (PBCA) nanoparticles (NPs) have been studied. Yet, little is known of how physiochemical features such as size, surfactants and surface charge influence BBB passage in vivo. We used a rat model of in vivo imaging of the retina - which is brain tissue and can reflect the situation at the BBB - to study how size and surface charge determine NPs ability to cross the blood-retina barrier (BRB). The result showed that for poloxamer 188-modified, DEAE-dextran-stabilized PBCA NPs, decreasing the average zeta-size from 272 nm to 172 nm by centrifugation reduced the BRB passage of the NPs substantially. Varying the zeta potential within the narrow range of 0 15 mV by adding di erent amounts of stabilizer revealed that 0 mV and 15 mV were less desirable than 5 mV which facilitated the BRB passage. Then we removed and imaged the retina of the rats ex vivo to observe the detailed location of the NPs in retina tissue. Similar as the in vivo result, the NPs with larger zeta-size and 5 mV surface charge accumulated more in the vessel wall and in retina ganglion cells. Interestingly, the NPs with 0 mV surface charge accumulated unevenly in vessel wall and some agglomerates attached on the surface of the vessel wall. We also collected blood, brain, heart, kidneys, liver, lungs and spleen of the rats. The biological distribution of NPs in blood and brain is comparable to the results of in vivo imaging of blood vessel and retina tissue. Thus, minor changes in design of nanocarriers can alter physicochemical parameters such as size or zeta potential, thus substantially influencing NPs biological distribution in vivo.
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