Drug complexation, in vitro release and cellular entry of dendrimers and hyperbranched polymers

Highly branched, functionalized polymers have potential to act as efficient drug carrier systems. Dendrimers are ideal candidates among model hyperbranched polymers because of their well-defined structure and high density of functional groups. Using ibuprofen as a model drug, we studied the interaction between the drug and Polyamidoamine (PAMAM) dendrimers (generations 3 and 4 with -NH2 functionality) and Perstrop Polyol (generation 5, hyperbranched polyester with -OH functionality). FTIR and NMR studies suggest that ibuprofen predominantly forms a complex with PAMAM dendrimers because of the ionic interaction between the -NH2 end groups and the carboxyl group of ibuprofen. On an average, up to 78 molecules of ibuprofen could be incorporated into one molecule of PAMAM-G4-NH2 with 64 end groups. This complex is stable in deionized water and methanol. The in vitro release of ibuprofen from drug-dendrimer complex is appreciably slower compared to pure ibuprofen. The complexed drug enters A549 cells much more rapidly than pure drug suggesting that dendrimers may be able to cam, the complexed drug inside cells efficiently. Hyperbranched Polyol (with 128 -OH end groups) appears to encapsulate approximately 24 drug molecules. Perhaps the lack of strong interactions between the -OH end groups and the drugs prevents complex formation. (C) 2003 Elsevier Science B.V. All rights reserved.