Preparation, cellular transport, and activity of polyamidoamine-based dendritic nanodevices with a high drug payload

Dendrimer-Encapsulated Camptothecins: Increased Solubility, Cellular Uptake, and Cellular Retention Affords Enhanced Anticancer Activity In vitro

“…The dendrimer could be acting as (a) a depot for the camptothecin which releases the camptothecin into the aqueous solution over time for subsequent uptake by the cells-but this proposal is not consistent with the data observed between cell lines and the DMSO controls; (b) a vehicle that transports the camptothecin to the cell membrane for subsequent passive absorption of the camptothecin or the camptothecindendrimer complex via the intracellular junctions-although this transport route is generally accepted for smaller materials of <1.5 nm (48); or (c) a vehicle and its cargo that is taken up by the endocytosis pathway. The last proposal is more likely and would be consistent with reports on anionic carboxylated PAMAM and hydroxyl terminated PAMAM dendrimers which are proposed to enter the cell through fluid-phase endocytosis (49,50). Cell trafficking studies with labeled dendrimer with and without the camptothecin are planned to elucidate the role of the dendrimer in the delivery of camptothecins.…”

“…Three replicates were tested for each concentration. For IC 50 determinations, the formulations were diluted serially in half-log steps. Blank wells and wells with media but no cells were included for background correction because trichloroacetic acid (TCA)-precipitated proteins from serum alone result in some background SRB absorbance.…”

“…Absorbance measured on wells containing cells that did not receive the drug represented 100% growth, and absorbance measured on wells containing no cells represented 0% growth. For IC 50 calculations, survival data were evaluated by variable slope curve-fitting using Prism 4.0 software (GraphPad, San Diego, CA).…”

Dendrimers in Cancer Treatment and Diagnosis

“…Unsurprisingly, based on these many beneficial features, a wide range of biologically active molecules have already been covalently attached to dendrimers. These conjugates range from small molecule drugs, such as ibuprofen [85], fluorescent and radioactive imaging agents (Section 1.6.4), oligonucleotides, oligosaccharides and peptides, as well as much larger molecules such as monoclonal antibodies (Section 1.6.3). Biologically active molecules attached to dendrimers can have two fundamentally different relationships to the host molecule.…”

“…Once inside a cell, there are early indications that the precise properties of a dendrimer can influence subcellular trafficking. Eventually, if these processes can be better understood and controlled, their exploitation for drug delivery will be very attractive considering that some entities, such as dendrimerdelivered ibuprofen, need to only gain access to the cytosol [85], whereas other class of drugs, such as dendrimer-delivered plasmid DNAs, have the moredemanding task of reaching the nucleus [104].…”