Carvalho Vanessa F, de Lemos Debora P, Vieira Camila S, Migotto Amanda, Lopes Luciana B
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, São Paulo, São Paulo, Brazil.
Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
AAPS PharmSciTech. 2017 Jul;18(5):1739-1749. doi: 10.1208/s12249-016-0643-7. Epub 2016 Oct 18.
In this study, non-aqueous microemulsions were developed because of the challenges associated with finding pharmaceutically acceptable solvents for topical delivery of drugs sparingly soluble in water. The formulation irritation potential and ability to modulate the penetration of lipophilic compounds (progesterone, α-tocopherol, and lycopene) of interest for topical treatment/prevention of skin disorders were evaluated and compared to solutions and aqueous microemulsions of similar composition. The microemulsions (ME) were developed with BRIJ, vitamin E-TPGS, and ethanol as surfactant-co-surfactant blend and tributyrin, isopropyl myristate, and oleic acid as oil phase. As polar phase, propylene glycol (MEPG) or water (MEW) was used (26% w/w). The microemulsions were isotropic and based on viscosity and conductivity assessment, bicontinuous. Compared to drug solutions in lipophilic vehicles, MEPG improved drug delivery into viable skin layers by 2.5-38-fold; the magnitude of penetration enhancement mediated by MEPG into viable skin increased with drug lipophilicity, even though the absolute amount of drug delivered decreased. Delivery of progesterone and tocopherol, but not lycopene (the most lipophilic compound), increased up to 2.5-fold with MEW, and higher amounts of these two drugs were released from MEW (2-2.5-fold). Both microemulsions were considered safe for topical application, but MEPG-mediated decrease in the viability of reconstructed epidermis was more pronounced, suggesting its higher potential for irritation. We conclude that MEPG is a safe and suitable nanocarrier to deliver a variety of lipophilic drugs into viable skin layers, but the use of MEW might be more advantageous for drugs in the lower range of lipophilicity.
在本研究中，由于难以找到可用于局部递送难溶于水的药物的药学上可接受的溶剂，因此开发了非水微乳剂。评估了制剂的刺激性潜力以及调节对局部治疗/预防皮肤疾病感兴趣的亲脂性化合物（孕酮、α-生育酚和番茄红素）渗透的能力，并与组成相似的溶液和水微乳剂进行了比较。以BRIJ、维生素E-TPGS和乙醇作为表面活性剂-助表面活性剂混合物，以三丁酸甘油酯、肉豆蔻酸异丙酯和油酸作为油相，开发了微乳剂（ME）。作为极性相，使用了丙二醇（MEPG）或水（MEW）（26%w/w）。这些微乳剂是各向同性的，基于粘度和电导率评估，为双连续结构。与亲脂性载体中的药物溶液相比，MEPG将药物递送至活皮肤层的能力提高了2.5至38倍；尽管递送的药物绝对量减少，但MEPG介导的进入活皮肤的渗透增强幅度随药物亲脂性增加。MEW使孕酮和生育酚的递送增加了2.5倍，但番茄红素（最亲脂性的化合物）未增加，并且这两种药物从MEW中释放的量更高（2至2.5倍）。两种微乳剂都被认为可安全用于局部应用，但MEPG介导的重建表皮活力降低更为明显，表明其具有更高的刺激性潜力。我们得出结论，MEPG是一种安全且合适的纳米载体，可将多种亲脂性药物递送至活皮肤层，但对于亲脂性较低的药物，使用MEW可能更具优势。
