Le Guyader Guillaume, Do Bernard, Rietveld Ivo B, Coric Pascale, Bouaziz Serge, Guigner Jean-Michel, Secretan Philippe-Henri, Andrieux Karine, Paul Muriel
Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, F-94010 Créteil, France.
Centre Hospitalier Intercommunal de Créteil, F-94010 Créteil, France.
Pharmaceutics. 2022 Mar 4;14(3):569. doi: 10.3390/pharmaceutics14030569.
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.
面部血管纤维瘤（FA）是结节性硬化症最明显的皮肤表现之一。外用雷帕霉素治疗血管纤维瘤已被报道是一种有前景的治疗方法。迄今为止，已使用了几种类型的载体，但聚合物胶束，尤其是由聚乙二醇1000琥珀酸酯-α-生育酚（TPGS）制成的聚合物胶束，似乎比目前常用的软膏显示出更好的雷帕霉素皮肤生物利用度。为了更好地理解聚合物胶束对雷帕霉素行为的影响，我们通过将TPGS和泊洛沙姆混合制成的聚合物胶束进行了探索，评估其稳定性和皮肤生物利用度，以确定一种有效治疗FA的优化配方。我们的研究表明，由于TPGS强烈包封在胶束中，它改善了雷帕霉素的物理化学行为，即其溶解度和稳定性，而泊洛沙姆P123对皮肤生物利用度有更显著的影响。因此，我们制备了含有0.1%雷帕霉素的混合胶束水凝胶，发现优化后的配方在2-8℃下可稳定保存3个月。此外，与水醇凝胶制剂相比，所研究的系统在人体皮肤上具有更好的生物分布。
