Formulation and clinical evaluation of hyaluronic acid nanogel in treatment of tear trough: nano-flipping from injectable fillers to topical nanofillers

Tear trough deformity (TTD) is a significant cosmetic concern, with current treatments relying primarily on invasive injectable fillers, which are costly and carry risks of complications. Despite the widespread use of hyaluronic acid (HA) in cosmetic applications, its poor dermal permeation has limited the development of effective topical fillers for TTD. This study aim to develop and evaluate a novel hyaluronic acid nanogel (nanofiller, NF) as a non-invasive topical filler for TTD. The hyaluronic acid NF was formulated and characterized for size, zeta potential, and skin permeation using the Franz diffusion method. The nanofiller demonstrated a particle size of 213.28 +/- 4.15 nm and a zeta potential of -22.1 +/- 1.07 mV, with a tenfold superior permeation compared to conventional HA gel. Thirty adult female patients aged 21-50 years with TTD were enrolled in a clinical trial and randomly assigned to receive either the NF or a conventional HA gel (control). Participants were randomly assigned to receive either the NF or a conventional HA gel (control). Clinical evaluation included subjective assessments and objective photomorphometric measurements of TTD parameters such as skin roughness (fine lines), indentation index, mean density, and percentage of the affected area. The NF group showed a significant improvement in TTD parameters, including up to a 40-fold reduction in skin roughness and indentation index, with 100% patient satisfaction and no adverse effects, compared to the control group. "To conclude; this study demonstrates the efficacy and safety of the HA nanofiller as the first effective topical treatment for TTD, offering a non-invasive alternative to injectable fillers.