Poly(amino acids) for drug and gene delivery

Three classes of biodegradable poly(amino acids) have been developed for the potential application to drug and gene delivery. Hyperbranched polylysine has been synthesized by four methods to obtain molecular weights up to 16,000 g/mol and degrees of branching approaching 0.64. The initial investigation into the DNA complexation capability of hyperbranched polylysine led to their use as “macro-cores” in the design of a second class of materials. These polymers were used to graft short linear polylysine chains to provide a macromolecule effective in DNA condensation, but ineffective in the release of the genetic material. To improve the delivery ability, histidine units were introduced into the polymer to provide imidazole units to promote DNA release. As expected, the histidine-containing materials formed weaker complexes with DNA compared to the all lysine polymer.; One class of molecules investigated for drug delivery are amphiphilic polymers that are degradeable and biocompatible such as the previously synthesized hydraamphiphiles consisting of a Boc-terminated lysine dendrimer grown from a monofunctional PEG chain. The asymmetric nature of the lysine repeat unit may prevent the hydrophobic end groups from perfectly aligning at the periphery since the termini are non-equivalent. To investigate the effect this has on the surfactant properties, a hydraamphiphile isomeric to the PEG supported lysine dendrimer has been synthesized using isolysine, the symmetric isomer of lysine, as the dendritic building block. The dendrimer was grown onto a PEG chain using a Boc-protected isolysine monomer, which was prepared in 5 steps from 2-pyrollidinone and 2-bromoethylamine hydrobromide. The surfactant properties of generations 1–4 of these Boc-terminated dendrimers were examined and compared to those previously obtained for the lysine dendrons. Micelle size was somewhat dependent on generation and dendrimer symmetry as were the critical micelle concentrations (cmcs) and micelle aggregation numbers. The stability of oil in water emulsions using the PEG supported Boc-terminated isolysine dendrimers as the surfactant was also explored.