Characterization and Optimization of PLA Stereocomplexed Hydrogels for Local Gene Delivery Systems

Localized gene delivery still remains as a challenging therapeutic method due to the multiple hurdles to overcome. One of the significant factors is a development of a matrix to carry and safely deliver genes at the local site in a controlled manner and then exit and disintegrate harmlessly. This report describes the structural and mechanistic studies on the in-situ forming hydrogels composed of the PEI/DNA multi-layered micelles to apply for gene therapy. The stereocomplexation-driven hydrogel systems from the DNA-loaded and DNA-free PLA-PEG-PLA triblock copolymer micelles that include enantiomeric polylactide blocks exhibited a sol-to-gel transitions between room and body temperatures. These hydrogels have well-described structure and compositions, and improved mechanical properties. Furthermore, the investigation of their degradation profiles and chemical analysis indicated the faster acidic degradation and stepwise degradation process of these micelle–hydrogel systems.