A self-destroying polycationic polymer: Biodegradable poly(4-hydroxy-L-proline ester)

A self-destroying, biodegradable, and polycationic polyester, poly(trans-3- hydroxy-L-proline ester) (PHP ester), was synthesized, and the interaction of the polymer with polyanion DNA was investigated. Degradation of the poly mer in aqueous solution was investigated by matrix-assisted laser desorptio n/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and by measuri ng the pH change as carboxylic acids are formed as products of the degradat ion of the polymer backbone ester bond. It was shown from MALDI-MS data tha t the polymer degraded to less than half of the intact polymer molecular we ight in less than 2 h. But a Blower degradation rate after initial rapid de gradation (within 1 day) was apparent. A self-destroying mechanism at the i nitial stage is proposed. The polymer was gradually degraded to near comple tion in 3 months in an aqueous solution to monomer, hydroxyproline, a major constituent of collagen, which could easily be detected by using MALDI-MS. Although the polymer degraded very quickly in an aqueous solution, it form ed stable PHP ester/DNA complexes by electrostatic interaction when the pol ymer was mixed with the polyanionic DNA solution. The condensation behavior of DNA with the polymer to form self-assembled PHP ester/DNA complexes was characterized by electrophoretic mobility shift assay, dynamic light scatt ering, xi potential, and nuclease resistance assay. These results show that PHP ester forms a strong complex with DNA by means of electrostatic intera ction. Transfection of beta-galactosidase gene into mammalian cell using PH P ester/DNA complexes was successful, showing the possibility of using PHP ester as a biodegradable gene delivery carrier.