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  • Title: Investigations on biodistribution of technetium-99m-labeled carbohydrate-coated poly(propylene imine) dendrimers.
    Author: Agashe HB, Babbar AK, Jain S, Sharma RK, Mishra AK, Asthana A, Garg M, Dutta T, Jain NK.
    Journal: Nanomedicine; 2007 Jun; 3(2):120-7. PubMed ID: 17572354.
    Abstract:
    The purpose of this work was to study the biodistribution pattern of the fifth generation of poly(propylene imine) dendrimer (PPI-5.0G)-based carbohydrate (mannose and lactose)-coated glycodendrimers in mice so as to explore the potential of these systems as drug carriers. Plain dendrimers were synthesized and coated with carbohydrates following the reported procedures. The formulations were labeled with radioactive technetium (sodium pertechnetate; 99mTcO4-) and characterized for labeling efficiency as well as in vitro and in vivo stability of the labeled complexes. The blood clearance study was performed in female New Zealand rabbits. The periodic in vivo biodistribution profile of the formulations was investigated in female Balb/c mice. The dendrimeric formulations were labeled with 95% labeling efficiency. The labeled complexes were found to be stable in vitro (97% to 98% stability) and in vivo (89% to 94% stability). All the formulations were cleared rapidly from circulation; clearance of mannose-coated poly (propylene imine) dendrimer (M-PPI) and lactose-coated poly(propylene imine) dendrimer (L-PPI) was faster than PPI-5.0G. All the formulations accumulated in liver to a significant extent, but only those with terminal carbohydrate moieties were retained for a longer period. Significant accumulation of PPI-5.0G and M-PPI was observed in kidneys as against very less activity in the case of L-PPI. Rapid clearance of the dendrimers was in accordance with the earlier reports. Higher and prolonged retention of M-PPI and L-PPI in liver was attributed to lectin-carbohydrate interactions. Lesser accumulation of L-PPI in kidneys was suggestive of its lesser excretion. This observation can be explained on the basis of the molecular weight of L-PPI, which was greater than the threshold of glomerular excretion. In general, it was observed that the carbohydrate-coated dendrimers were distributed in liver to a significant extent. This information could serve as a useful platform in designing carbohydrate-coated dendrimers for selective delivery of bioactive agents to liver.
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