A biocompatible polyester dendrimer composed of the natural metabolites, glycerol and succinic acid, is described for the encapsulation of the antitumor camptothecins, 10-hydroxycamptothecin and 7-butyl-10-aminocamptothecin. The cytotoxicity of the dendrimer-drug complex toward four different human cancer cell lines [human breast adenocarcinoma (MCF-7), colorectal adenocarcinoma (HT-29), non-small cell lung carcinoma (NCI-H460), and glioblastoma (SF-268)] is also reported, and low nmol/L IC 50 values are measured. Cellular uptake and efflux measurements in MCF-7 cells show an increase of 16-fold for cellular uptake and an increase in drug retention within the cell when using the dendrimer vehicle.

Reichardt's dye, a highly solvatochromic dye, was encapsulated within poly (glycerol succinic acid) ([Gn]-PGLSA-OH) dendrimers to investigate the interior environment of these dendritic macromolecules. The absorption maximum for the encapsulated Reichardt's dye in water was indicative of a relatively high dielectric constant present within the dye/dendrimer complex. (1)H NMR of the encapsulated complex showed the presence of aromatic protons from Reichardt's dye along with the aliphatic protons of the dendrimer. Additionally, there were substantial changes in T(1) and T(2) times of the encapsulated dye when compared with the free dye, and (1)H NOESY spectra for the complex showed a significant number of intermolecular NOE cross-peaks. These data reveal the close through-space proximity of the dye to the dendrimer and the restricted motion of the encapsulated dye. To demonstrate the potential use of these macromolecules as drug delivery vehicles, the poorly water-soluble anticancer drug 10-hydroxycamptothecin (10HCPT) was encapsulated within a carboxylated PGLSA dendrimer ([G4]-PGLSA-COONa). Cytotoxicity assays with human breast cancer cells showed a significant reduction of cell viability, demonstrating that 10HCPT retains activity upon encapsulation.

Hyaluronan-based scaffolds are of interest for tissue-engineered cartilage repair due to an important role for hyaluronan in cartilage development and function. In this study, an in situ photocrosslinkable hyaluronan (HA-MA) was developed and evaluated as a scaffold for articular cartilage repair. Chondrocytes were encapsulated in crosslinked HA-MA and evaluated for their ability to synthesize cartilaginous matrix in vitro. The mechanical and physical properties of the crosslinked HA-MA hydrogels were similar to that of other hydrogels, with compressive and dynamic shear moduli of 0.6 and 0.3 kPa, respectively, and diffusion coefficients of 600-8000 microm2/s depending on molecular weight. Chondrocytes remained rounded in the HA-MA hydrogels in vitro, and accumulated significant amounts of cartilaginous matrix. Osteochondral defects filled with HA-MA were infiltrated with cells, appeared to integrate well with native tissue, and also accumulated substantial cartilaginous matrix by 2 weeks after surgery. In summary, photocrosslinkable HA-MA promoted the retention of the chondrocytic phenotype and cartilage matrix synthesis for encapsulated chondrocytes in vitro and accelerated healing in an in vivo osteochondral defect model.

Dendritic supramolecular assemblies were formed in water with Reichardt's dye or the anticancer drug 10-hydroxycamptothecin and the dendritic macromolecule, ([G4]-PGLSA-OH)2-PEG3400.