Müller Felix, Hönzke Stefan, Luthardt Wulf-Ole, Wong Ee Lin, Unbehauen Michael, Bauer Jörg, Haag Rainer, Hedtrich Sarah, Rühl Eckart, Rademann Jörg
Institute of Pharmacy, Medicinal Chemistry, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany.
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany.
Eur J Pharm Biopharm. 2017 Jul;116:31-37. doi: 10.1016/j.ejpb.2016.12.013. Epub 2016 Dec 21.
Bacterial biosurfactants are nature's strategy to solubilize and ingest hydrophobic molecules and nutrients using a fully biodegradable transport system. Eight structurally defined rhamnolipids were selected and investigated as potential drug carrier systems. Depending on the molecular structures defining their packing parameters, the rhamnolipids were found to form spherical nanoparticles with precisely defined average sizes between 5 and 100nm, low polydispersity, and stability over a broad concentration range as revealed from dynamic light scattering and electron microscopy. As rhamnolipids were tolerated well by the human skin, rhamnolipid nanoparticles were considered for dermal drug delivery and thus loaded with hydrophobic drug molecules. Using the drug model, Nile red, dexamethasone, and tacrolimus nanoparticles charged with up to 30% drug loading (w/w) were obtained. Nanoparticles loaded with Nile red were investigated for dermal drug delivery in a Franz cell using human skin. Fluoresence microscopy of skin slices indicated the efficient penetration of the model drug into human skin, both into the stratum corneum and although to a lesser extent into the lower epidermis. Rhamnolipid nanocarriers were found to be non-toxic to primary human fibroblasts in a proliferation assay and thus are considered candidates for the dermal delivery of drugs.
细菌生物表面活性剂是自然界利用完全可生物降解的运输系统来溶解和摄取疏水分子及营养物质的策略。选择了八种结构明确的鼠李糖脂并将其作为潜在的药物载体系统进行研究。根据定义其堆积参数的分子结构，通过动态光散射和电子显微镜观察发现，鼠李糖脂能形成平均尺寸在5至100纳米之间、多分散性低且在较宽浓度范围内稳定的球形纳米颗粒。由于人体皮肤对鼠李糖脂耐受性良好，因此考虑将鼠李糖脂纳米颗粒用于皮肤给药，并使其负载疏水性药物分子。使用药物模型尼罗红、地塞米松和他克莫司，获得了药物负载量高达30%（w/w）的纳米颗粒。使用人体皮肤在弗兰兹扩散池（Franz cell）中对负载尼罗红的纳米颗粒进行皮肤给药研究。皮肤切片的荧光显微镜检查表明，模型药物能有效渗透到人体皮肤中，既进入角质层，也能进入下层表皮，尽管程度较小。在增殖试验中发现鼠李糖脂纳米载体对原代人成纤维细胞无毒，因此被认为是皮肤给药的候选材料。
