Dendrimers biodistribution

Antibodies are powerful tools in pharmaceutical development, and as den-drimers are incorporated into various drugs and medical devices, antibodies such as described should be useful to study dendrimer biodistribution and pharmacokinetic properties. We have not attempted to detect PAMAM de-ndrimers in biological fluids (blood, urine, sputum, etc.), but expect that it would work. Additionally, the antibodies might be used in immunohistochemistry to study the tissue and cellular distribution of dendrimer therapeutics. 

Kobayashi, H., Wu, C., Kim, M.K., Paik, C.H., Carrasquillo, J.A., and Brechbiel, M.W. (1999) Evaluation of the in vivo biodistribution of indium-111 and yttrium-88 labeled dendrimer-1 B4M-DTPA and its conjugation with anti-Tac monoclonal antibody. Bioconjug. Chem. 10, 103-111. 

Gadolinium-dendrimer conjugates have been used as blood pool contrast agents in vivo for nuclear magnetic resonance imaging (MRI) of tumors [65]. The efficacy of the conjugates in such applications is dependent on their biodistribution properties, and these properties vary as a function of dendrimer molecular weight and chemical composition [50]. Dendrimer architecture and synthesis... 

The application of dendritic polymers as drug delivery systems has gained interest mainly due to their inertness relative to temperature, solvent, and pH extremes [38]. However, dendritic polymers require further improvements in biocompability and biodistribution profiles. The cytotoxicity of dendrimers currently has been primarily studied in vitro. 

Malik, N., et al. 2000. Dendrimers Relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 1251-labelled polyamidoamine dendrimers in vivo. 

Roberts, J.C. Bhalgat, M.K. Zera, R.T. Preliminary biological evaluation of polyamidoamine (PAMAM) star-burst dendrimers. J. Biomed. Mater. Res. 1996, 30, 53-65. Malik, N. Wiwattanapatapee, R. Klopsch, R. Lorenz, K. Frey, H. Weener, J.W. Meijer, E.W. Paulus, W. Duncan, R. Dendrimers relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of l-Labeled polyamidoamine dendrimers in vivo. J. Control. Release 2000, 65, 133-148. 

S.T. Lo, S. Stem, J.D. Clogston, J. Zheng, P.P. Adiseshaiah, M. Dobrovolskaia, J. Lim, A.K. Patri, X. Sun, E.E. Simanek, Biological assessment of triazine dendrimer toxicological profiles, solution behavior, biodistribution, drug release and efficacy in a PEGylated, paclitaxel construct. Mol. Pharm. 7 (4) (2010) 993-1006. 

The pharmacokinetics and biodistribution of dendrimers primarily depend on their size and surface composition. While lower generation dendrimers are more rapidly cleared through renal clearance due to lower molecular weight and smaller size, larger dendrimers induce more effective uptake by the RES and leads to increased RES clearance.[76,77] With an increase of PAMAM dendrimer generation (G2-G9), plasma circulation time increases, peaking at G7.[78,79] Due to the increased uptake of G8 and G9 dendrimers in liver and spleen, their plasma circulation times were reported to be shorter than that of G7. 

The size of dendritic supramolecules and hybrid nanoparticles (typically 20-200 nm in diameter) affects their biodistribution in vivo. As their hydrodynamic diameters are larger than threshold of kidney ( 5.5 nm), their elimination rate from the body is typically slower and circulation time in the body is longer than dendrimers.[80] Another clearance mechanism via RES following intravenous administration is inversely dependent on their size, i.e., more efficient macrophage uptake of 90 nm nanoparticles than that of 15 nm nanoparticles.[81]... 

Boyd, B.J., Kaminskas, L.M., Karellas, P., Krippner, G., Lessene, R., Porter, C.J.H. Cationic poly-L-lysine dendrimers Pharmacokinetics, biodistribution, and evidence for metabolism and bioresorption after intravenous administration to rats. Mol. Pharmaceut. 3(5), 614-627 (2006). doi 10.1021/Mp060032e... 

Dendrimers offer precise control over pharmacokinetics and biodistribution (BioD), which is achieved by tuning dendrimer size, conformation, and surface function. 

In general, at least three major (hydrophobicity, electronic, and steric) parameters and possibly other minor parameters (such as rigidity, adaptability of the dendrimers, etc) influence biodistribution. However, we will not be able to study all the parameters unless we have a working model, and perform all the necessary in vivo experiments. There is no systematic study on the effect of hydrophilicity. Electronic factors are characterized by charge — as described by the zeta potential of the particle,... 

DISPOSITION OF DENDRIMER COMPOSITE NANOPARTICLES (CELLULAR UPTAKE, BIODISTRIBUTION AND EXCRETION)... 

We have previously published on the detailed biodistribution of tritium-labeled 5nm dendrimers with neutral and positive-charged surface. This was the first quantitative biodistribution data on dendrimers in tumor model systems, and we found that both dendrimers cleared rapidly from blood, and localized to... 

Chandrasekar, D., R. Sistla, R J. Ahmad, R. K. Khar, and P V. Diwan. 2007. The development of folate-PAMAM dendrimer conjugates for targeted delivery of anti-arthritic drugs and their pharmacokinetics and biodistribution in arthritic rats. Biomaterials 28(3) 504-12. 

PEGylation of the PEL dendrimers results in enhanced control over the pharmacokinetics and degradability of these materials, as well as the biodistribution, and rate of renal clearance. " The blood circulation ti/2 of the dendrimer could be manipulated based on the MW of the peripheral PEG chains that are conjugated to the PEL core. 

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