Abstract
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.
Highlights
Localized gene therapy approaches have found increasing popularity in the fields of tissue engineering, immune therapy, localized disease therapy, long-term depots for drugs, and localized site production “factories” for proteins [1,2,3]
The hydrogel systems with a sol-to-gel transition at the desired temperature were obtained by optimizing the polymer concentration in the system and weight ratio of inner:outer polymers (PLLA-PEI-PLLA/PLLA-polyethylene glycol (PEG)-PLLA) during the 3-layered micelle (3LM) formation
The mechanical strength of the hydrogels improved through the use of PDLA-PEG-PDLA micelles with mixed PEG block length
Summary
Localized gene therapy approaches have found increasing popularity in the fields of tissue engineering, immune therapy, localized disease therapy, long-term depots for drugs, and localized site production “factories” for proteins [1,2,3]. Hydrogels have been utilized as coating materials for implants, intravascular stents, thin films (membrane), porous scaffolds, and in-situ forming hydrogel depots. Hydrogels are produced outside of the body (after incorporating genetic material), and implanted into the body. The disadvantage of such approach is that the matrix must be implanted through surgical means. Some of the advantages of these injectable delivery systems include minimal invasiveness and surgery related complication, and the materials can be molded to fit specific shapes and crevices [4,5]
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