Chapter 5. Mitochondria Targeting Nanogel System for Drug Delivery
5.5 Conclusions and Future Work
In this research, we synthesize mitochondrial target ligand start from hexaethylene glycol. The ethylene glycol moiety was expected to show high flexibility with biocompatibility in the biological environment. Each end of ligand was modified with mitochondrial targeting functional group. The ligand molecule was assigned by proton NMR spectroscopy. The thiol group of the ligand molecule performed thiol exchange on the surface of self-crosslinked nanogel.
Simple solvent displacement method was performed to encapsulate model drug molecule.
Successful encapsulation in the self-crosslinked nanogel was identified through UV spectroscopy. In this system, DTT was treated for surface crosslinking. However, DiI and DiO co-encapsulated model showed poor surface modification degree with unknown reason. There are several hypotheses regarding this result. In this system, if DiO molecule was not encapsulated in the core of nanogel, but intercalate with polymer molecule makes inhibit to thiol-exchange reaction between surface of nanogel and targeting ligand molecule. The amount of DTT for cross-linking of nanogel also can be the other reason of this phenomenon. To make clear the reason of this result, further experiments regarding DTT concentration is planned to be performed.
Finally, the ability of targeting mitochondria was investigated through confocal microscopy. The result indicates that the nanogel system has an effect on delivering their cargo to mitochondria.
Through this result, we planned detail experiments to get more clear evidence by adjusting concentration of nanogel solution. Further investigation with drug molecule and targeting efficiency will be examined as future work with in vivo experiments.
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