ROUTE-DEPENDENT ASTAXANTHIN DELIVERY MODULATES GRANULOCYTE MITOCHONDRIAL STRESS RESPONSES

Astaxanthin is a potent natural lipophilic antioxidant with mitochondrial protective and anti-inflammatory properties. Its oral bioavailability is limited by poor aqueous solubility and first-pass metabolism. Alternative delivery routes may alter systemic and cellular availability. We aimed to compare the effects of sublingual, transdermal, and oral astaxanthin administration on granulocyte functional parameters associated with mitochondrial stress.

A prospective comparative study included 60 healthy volunteers divided into three groups (n=20 per group). Participants received astaxanthin for 30 days by sublingual administration (6 mg/day), transdermal administration (6 mg/day), or oral administration (12 mg/day). Granulocyte phenotypic profiling was performed at baseline and after one month using fluorescence microscopy. The assessed parameters included mitochondrial activity, protein metabolism, oxidative stress, oxygen and energy metabolism, and phagocytic activity. Mitochondrial activity was evaluated by the proportion of cells demonstrating mitochondrial accumulation, while oxidative stress was assessed based on spontaneous membrane damage. Oxygen metabolism was evaluated using the nitroblue tetrazolium (NST) test, and phagocytic activity using a latex particle assay.

Sublingual and transdermal administration produced greater improvements than oral administration. Mitochondrial activity increased by 25, 22, and 11 percentage points, respectively; protein metabolism by 22, 21, and 11 points; oxygen and energy metabolism by 13, 11, and 7 points; and phagocytic activity by 8, 6, and 4 points. Oxidative stress decreased by 21, 18, and 10 points, respectively. The greatest improvements in mitochondrial activity and reductions in oxidative stress were observed following sublingual and transdermal delivery.

The route of astaxanthin administration influences granulocyte mitochondrial and functional responses. Sublingual and transdermal delivery were associated with greater improvements in mitochondrial activity, metabolic function, oxygen metabolism, and phagocytic activity, together with reduced oxidative stress, compared with oral administration. Granulocyte phenotypic profiling may provide a functional approach for evaluating antioxidant delivery strategies and formulations aimed at mitochondrial protection.