Fernandes B, Silva R, Ribeiro A, Matamá T, Gomes A C, Cavaco-Paulo A M
Centre of Biological Engineering (CEB), University of Minho, Campus of Gualtar, 4710-057, Braga, Portugal.
Int J Cosmet Sci. 2015 Jun;37(3):282-90. doi: 10.1111/ics.12197. Epub 2015 Jan 29.
Hair follicles are widely recognized as the preferential target and site of accumulation for nanoparticles after topical application. This feature is of particular importance for hair cosmetics, having the potential to refine the treatment of several hair follicle-related disorders. The aim of this work was to improve the preparation of Poly (D,L-lactide) (PLA) nanoparticles for in vivo follicular target and drug delivery.
Envisaging a future industrial scale-up of the process, nanoprecipitation method was used to prepare PLA nanoparticles: the effect of several processing parameters on their properties was examined and the yield of nanoparticles formation determined. Encapsulation efficiencies and in vitro release profiles of lipophilic and hydrophilic model compounds were also assessed. In vitro cytotoxicity and ex vivo penetration studies were performed on a reference skin cell line (NCTC2455, human skin keratinocytes) and porcine skin, respectively.
Using acetone : ethanol (50 : 50, v/v) as the solvent phase, 0.6% (w/w) of Pluronic(®) F68 as a surfactant agent and agitation to mix the solvent and non-solvent phases, a monodispersed population of non-cytotoxic spherical nanoparticles of approximately 150 nm was obtained. The yield of nanoparticles for this formulation was roughly 90%. After encapsulation of model compounds, no significant changes were found in the properties of particles and the entrapment efficiencies were above 80%. The release kinetics of dyes from PLA nanoparticles indicate an anomalous transport mechanism (diffusion and polymer degradation) for Nile Red (lipophilic) and a Fickian diffusion of first order for fluorescein 5(6)-isothiocyanate (hydrophilic). Ex vivo skin penetration studies confirmed the presence of nanoparticles along the entire follicular ducts.
The optimized method allows the preparation of ideal PLA nanoparticles-based formulations for hair follicle targeting. PLA nanoparticles can effectively transport and release lipophilic and hydrophilic compounds into the hair follicles, and the yields obtained are acceptable for industrial purposes.
毛囊被广泛认为是局部应用后纳米颗粒的优先靶向和蓄积部位。这一特性对于毛发化妆品尤为重要，有可能改善几种毛囊相关疾病的治疗。本研究的目的是改进聚（D，L-丙交酯）（PLA）纳米颗粒的制备方法，用于体内毛囊靶向和药物递送。
考虑到该工艺未来的工业放大，采用纳米沉淀法制备PLA纳米颗粒：研究了几个工艺参数对其性能的影响，并测定了纳米颗粒形成的产率。还评估了亲脂性和亲水性模型化合物的包封效率和体外释放曲线。分别在参考皮肤细胞系（NCTC2455，人皮肤角质形成细胞）和猪皮肤上进行了体外细胞毒性和离体渗透研究。
以丙酮：乙醇（50：50，v/v）为溶剂相，0.6%（w/w）的普朗尼克（®）F68作为表面活性剂，搅拌混合溶剂相和非溶剂相，得到了单分散的、非细胞毒性的球形纳米颗粒，粒径约为150nm。该配方纳米颗粒的产率约为90%。模型化合物包封后，颗粒性能无明显变化，包封率均在80%以上。PLA纳米颗粒中染料的释放动力学表明尼罗红（亲脂性）的转运机制为异常转运（扩散和聚合物降解），而异硫氰酸荧光素5（6）（亲水性）的转运机制为一级菲克扩散。离体皮肤渗透研究证实纳米颗粒存在于整个毛囊管中。
优化后的方法可制备出理想的基于PLA纳米颗粒的毛囊靶向制剂。PLA纳米颗粒能有效地将亲脂性和亲水性化合物转运并释放到毛囊中，所得产率对于工业应用来说是可以接受的。
