Mixed Polymeric Micelles for Rapamycin Skin Delivery.

Bernard Do,Serge Bouaziz,Philippe-Henri Secretan,Guillaume Le Guyader,Karine Andrieux,Pascale Coric,Ivo B Rietveld,Jean-Michel Guigner,Muriel Paul

doi:10.3390/pharmaceutics14030569

Abstract

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.

Highlights

Introduction iationsTuberous sclerosis complex (TSC) is an autosomal dominant disorder, characterized by formation of hamartomas in various organs [1]
The results showed the influence of the vehicle and the thermodynamic activity on the cutaneous bioavailability of rapamycin
The inclusion of rapamycin in micelles was demonstrated by ATR-Fourier Transform Infrared Spectroscopy (FTIR) and

Summary

Introduction

Introduction iationsTuberous sclerosis complex (TSC) is an autosomal dominant disorder, characterized by formation of hamartomas in various organs [1]. Among the associated clinical signs, facial angiofibromas (FA) are one of the most obvious cutaneous manifestations of TSC, which can be disfiguring, causing substantial psychological distress with a major impact on quality of life [3,4]. Invasive procedural treatments such as surgery or laser involve pain and hypertrophic scars and are not entirely satisfactory due to the recurrence of skin lesions [4,5]. For this reason, medical treatment with topical rapamycin has so far been a studied option.

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