In situ gel forming graft copolymers of a polyaspartamide and polylactic acid: Preparation and characterization

In situ gel forming systems have been prepared by linking polylactic acid (PLA) to a water soluble and polyfunctional polymer, such as α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA). Three graft copolymers PHEA-PLA with a different derivatization degree in PLA, have been synthesized and characterized. PHEA-PLA graft copolymer with the highest amount in PLA has been used to prepare solutions in organic solvents able to give rise to gel-like matrices when injected into phosphate buffered saline solution. The chemical degradation of these gels has been evaluated and in vitro tests have been performed to evaluate the cell compatibility of the hydrolysis products. The possibility to use these gels for drug release has been investigated by incorporating leuprolide as a peptide model drug and by evaluating its in vitro release. To improve the drug release profile, PHEA-PLA graft copolymer has been derivatized with pendant carboxylic groups that are able to form an ion pair with the leuprolide thus reducing the burst effect and prolonging its release.