Hyaluronan-Based Nanohydrogels as Effective Carriers for Transdermal Delivery of Lipophilic Agents: Towards Transdermal Drug Administration in Neurological Disorders

We suggest a convenient nanoemulsion fabrication method to create hyaluronan (HA)-based nanohydrogels for effective transdermal delivery. First, hyaluronan-conjugated dodecylamine (HA-Do) HA-based polymers to load the lipophilic agents were synthesized with hyaluronan (HA) and dodecylamine (Do) by varying the substitution ratio of Do to HA. The synthetic yield of HA-Do was more than 80% (HA-Do (A): 82.7 +/- 4.7%, HA-Do (B): 87.1 +/- 3.9% and HA-Do (C): 81.4 +/- 4.5%). Subsequently, nanohydrogels were fabricated using the nanoemulsion method. Indocyanine green (ICG) simultaneously self-assembled with HA-Do, and the size depended on the substitution ratio of Do in HA-Do (nanohydrogel (A): 118.0 +/- 2.2 nm, nanohydrogel (B): 121.9 +/- 11.4 nm, and nanohydrogel (C): 142.2 +/- 3.8 nm). The nanohydrogels were delivered into cells, and had excellent biocompatibility. Especially, nanohydrogel (A) could deliver and permeate ICG into the deep skin layer, the dermis. This suggests that nanohydrogels can be potent transdermal delivery systems.