Kojic acid (KA) as tyrosinase inhibitor shows insufficient skin penetration and several adverse events due topical administration. KA solid lipid nanoparticles (KA-SLNs) were prepared using high speed homogenisation followed by ultra-probe sonication method for improve its effectiveness.KA-SLNs was optimised by Glyceryl mono-stearate (GMS) and Cholesterol (Chol) as lipid excipients and span 60 (SP 60) and Tween 20 (Tw 20) as co-emulsifiers (particle size 156.97 ± 7.15 nm, encapsulation efficiency 59.02 ± 0.74%, drug loading 14.755 ± 1.63%, polydispersity index (PDI) of 0.388 ± 0.004 and zeta potential (ZP) of -27.67 ± 1.89 mV). Optimum formulation (KA-SLN3 dispersion) was stable at 4 and 25 °C for 3 months. Also, TEM image confirmed these results. The results of XRD, DSC and ATR-FTIR analysis indicated that KA was well encapsulated within the SLNs either in molecularly dispersed state and stabilised in amorphous form and there was no chemical interaction between drug and other ingredients. Controlled release was achieved with this formulation. KA-SLN3 dispersion have more tyrosinase inhibition potency in comparison with pure KA. Also, the results of the ex vivo and in vitro percutaneous absorption show that KA-SLN3 dispersion improved percutaneous delivery of KA as a promising and potential novel topical preparation and might open new avenues for treatment of hyperpigmentation disorders.

中文翻译：

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脂质研究中的一种新兴技术，用于在过度色素沉着疾病的治疗中将亲水性药物靶向皮肤：曲酸-固体脂质纳米颗粒。

作为酪氨酸酶抑制剂的曲酸（KA）显示出不足的皮肤渗透性和局部给药引起的一些不良事件。采用高速均质化和超探针超声处理的方法制备KA固体脂质纳米粒（KA-SLNs）以提高其有效性。甘油单硬脂酸甘油酯（GMS）和胆固醇（Chol）作为脂质赋形剂和跨度优化了KA-SLNs 60（SP 60）和Tween 20（Tw 20）作为辅助乳化剂（粒径156.97±7.15 nm，包封效率59.02±0.74％，载药量14.755±1.63％，多分散指数（PDI）为0.388±0.004和zeta电位（ZP）为-27.67±1.89 mV）。最佳配方（KA-SLN3分散液）在4和25°C下稳定3个月。另外，TEM图像证实了这些结果。XRD的结果 DSC和ATR-FTIR分析表明，KA以分子分散状态很好地封装在SLN中，并以无定形形式稳定，并且药物与其他成分之间没有化学相互作用。用该制剂实现了控释。与纯KA相比，KA-SLN3分散液具有更强的酪氨酸酶抑制能力。同样，离体和体外经皮吸收的结果表明，KA-SLN3分散体改善了KA的经皮递送，这是一种有前途和潜在的新型局部制剂，并且可能为治疗色素沉着过度开辟新的途径。与纯KA相比，KA-SLN3分散液具有更强的酪氨酸酶抑制能力。同样，离体和体外经皮吸收的结果表明，KA-SLN3分散体改善了KA的经皮递送，这是一种有前途和潜在的新型局部制剂，并且可能为治疗色素沉着过度开辟新的途径。与纯KA相比，KA-SLN3分散液具有更强的酪氨酸酶抑制能力。同样，离体和体外经皮吸收的结果表明，KA-SLN3分散体改善了KA的经皮递送，这是一种有前途和潜在的新型局部制剂，并且可能为治疗色素沉着过度开辟新的途径。