PDF(Pubmed)
Abstract：
With increasing longevity globally, the search for effective and patient-friendly anti-aging solutions has been growing. Retinoic acid (Ret) is an FDA-approved anti-aging and anti-wrinkling formula, however, its poor solubility and poor tolerability hamper its use in cosmetically accepted formulations. In this study, cyclodextrins and arginine were investigated for improving the solubility and tolerability of retinoic acid through the formation of inclusion complexes and salt formation, respectively. Two different methods were employed: physical mixing and kneading. The prepared dispersions were investigated for molecular docking (MD), solubility, thermal and spectral analyses, cytotoxicity, and scratch assays. The optimized disperse systems were formulated in a gel formulation and characterized for rheological, in vitro release, and kinetics. The MD, DSC, and FTIR results indicated that both β- and hydroxy propyl (HP) β-cyclodextrins could host RA in their cavities and form inclusion complexes. Ret can form a salt with the basic amino acid arginine. Solubility studies of RA significantly (p < 0.01) enhanced by 14- to 81-fold increases with the investigated cyclodextrins and arginine. The cell viability recorded for Ret:HP β-CD K and Ret:arginine K was significantly increased compared to that for Ret alone. The IC50% recorded for azelaic acid (mild to non-irritant control), Ret, Ret:HP β-CD K, and Ret:arginine K were 1000, 485, 1100, and 895 µg/mL, respectively. The two carriers (HP β-CD and the amino acid arginine) were able to significantly (p < 0.05) reduce the irritation potential of Ret. Furthermore, comparable gap closure rates were recorded for Ret alone, Ret:HP β-CD K, and Ret:arginine K, indicating that inclusion complexation and ion pair formation reduced the irritation potentials without undermining the efficacy.
摘要：
随着全球寿命的延长，寻求有效和对患者友好的抗衰老解决方案的人数一直在增长。维甲酸（Ret）是FDA批准的抗衰老和抗皱配方，然而,其溶解性差和耐受性差妨碍其在化妆品接受的制剂中的使用。在这项研究中,研究了环糊精和精氨酸通过形成包合物和盐形成来改善视黄酸的溶解度和耐受性，分别。采用两种不同的方法:物理混合和捏合。研究了制备的分散体的分子对接（MD），溶解度，热和光谱分析，细胞毒性，和划痕试验。优化的分散系统配制在凝胶制剂中，并表征了流变学，体外释放，和动力学。MD,DSC,和FTIR结果表明，β-和羟丙基（HP）β-环糊精均可在其空腔中容纳RA并形成包合物。Ret可以与碱性氨基酸精氨酸形成盐。RA的溶解度研究随着所研究的环糊精和精氨酸显著增加14至81倍(p<0.01)。与单独的Ret相比，Ret：HPβ-CDK和Ret：精氨酸K记录的细胞活力显着增加。壬二酸的IC50（轻度至无刺激性对照），Ret,Ret:HPβ-CDK,和Ret：精氨酸K分别为1000、485、1100和895µg/mL，分别。两种载体（HPβ-CD和氨基酸精氨酸）能够显着（p<0.05）降低Ret的刺激潜力。此外，仅Ret记录了可比的间隙闭合率，Ret:HPβ-CDK,和Ret：精氨酸K，表明包合络合和离子对的形成降低了刺激电位，而不损害功效。
