PEG-fibrinogen Hydrogel Controlled Release System Of Antisense Oligonucleotide for the Treatment of Duchenne Muscular Dystrophy

Therapy based on antisense oligonucleotide (AON) mediated exon-skipping is one of the most promising therapeutic strategies for treating Duchenne Muscular Dystrophy (DMD). Although much effort is underway in searching for optimal delivery systems for AONs, many disadvantages are still presented in terms of their clinical use. In this research, we developed an AON delivery system based on PEG-fibrinogen (PF) hydrogel microspheres for intramuscular injection. The microspheres were fabricated by a dual-photo-initiator, emulsion-based technique and characterized for their size and morphology. We investigated the effects of increased cross-linking on the encapsulation of AONs and the AONs release rate from the hydrogel. The cellular uptake and localization of AONs in mouse-derived C2C12 muscle cells were determined using confocal microscopy. The results indicated that the PEG-fibrinogen microspheres were spherical, with a diameter of approximately 90 µm and with a biphasic release profile of AONs. Cell penetration study demonstrated that AONs released from the microspheres well penetrated into the cells, indicating that this PF microspheres delivery system could represent a potential therapy for DMD.