Facial
angiofibromas (FA) are one of the most obvious cutaneous manifestations of
tuberous sclerosis complex. Topical
rapamycin for
angiofibromas has been reported as a promising treatment. Several types of vehicles have been used hitherto, but polymeric
micelles and especially those made of d-α-
tocopherol polyethylene glycol 1000 succinate (
TPGS) seem to have shown better skin bioavailability of
rapamycin than the so far commonly used
ointments. To better understand the influence of polymeric
micelles on the behavior of
rapamycin, we explored it through mixed polymeric
micelles combining
TPGS and
poloxamer, evaluating stability and skin bioavailability to define an optimized formulation to effectively treat FA. Our studies have shown that
TPGS improves the physicochemical behavior of
rapamycin, i.e., its solubility and stability, due to a strong inclusion in
micelles, while
poloxamer P123 has a more significant influence on skin bioavailability. Accordingly, we formulated mixed-
micelle hydrogels containing 0.1%
rapamycin, and the optimized formulation was found to be stable for up to 3 months at 2-8 °C. In addition, compared to hydroalcoholic gel formulations, the studied system allows for better biodistribution on human skin.