Zaid Alkilani Ahlam, Alkhaldi Rua'a, Basheer Haneen A, Amro Bassam I, Alhusban Maram A
Department of Pharmacy, Faculty of Pharmacy, Zarqa University, Zarqa 13110, Jordan.
Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, The University of Jordan, Amman 11941, Jordan.
Pharmaceutics. 2025 Jan 2;17(1):48. doi: 10.3390/pharmaceutics17010048.
: The demand for a safe compound for hyperpigmentation is continuously increasing. Bioactive compounds such as thymoquinone (TQ) and ascorbic acid (AA) induce inhibition of melanogenesis with a high safety profile. The aim of this study was to design and evaluate spanlastics gel loaded with bioactive agents, TQ and AA, for the management of hyperpigmentation. : Several spanlastics formulations were successfully fabricated and characterized in terms of morphology, vesicle size, zeta potential, and release. : The optimized TQ-loaded spanlastic formulation showed an average size of 223.40 ± 3.50 nm, and 133.00 ± 2.80 nm for AA-loaded spanlastic formulation. The optimized spanlastics formulation showed the highest entrapment efficiency (EE%) of 97.18 ± 2.02% and 93.08 ± 1.95%, for TQ and AA, respectively. Additionally, the edge activator concentration had a significant effect ( < 0.05) on EE%; it was found that by increasing the amount of EA, the EE% increases. Following that, the optimal spanlastics fomulation loaded with TQ and AA were incorporated into gel and explored for appearance, pH, spreadability, stability, rheology, in vitro release, ex vivo permeation study, and MTT cytotoxicity. The formulated spanlastics gel (R-1) has a pH of 5.53. Additionally, R-1 gel was significantly ( < 0.05) more spreadable than control gel, and exhibited a shear thinning behavior. Most importantly, ex vivo skin deposition studies confirmed superior skin deposition of TQ and AA from spanlastic gels. Additionally, results indicated that tyrosinase inhibition was primarily due to TQ. When comparing TQ alone with the TQ-AA combination, inhibition ranged from 18.35 to 42.73% and 24.28 to 42.53%, respectively. Both TQ spanlastics and the TQ-AA combination showed a concentration-dependent inhibition of tyrosinase. : Spanlastic gel might represent a promising carrier for the dermal delivery of TQ and AA for the management of hyperpigmentation conditions.
对用于色素沉着过度的安全化合物的需求持续增长。诸如百里醌（TQ）和抗坏血酸（AA）等生物活性化合物可诱导黑色素生成的抑制，且具有高安全性。本研究的目的是设计并评估负载生物活性剂TQ和AA的弹性脂质体凝胶用于色素沉着过度的治疗。成功制备了几种弹性脂质体制剂，并对其形态、囊泡大小、zeta电位和释放情况进行了表征。负载TQ的优化弹性脂质体制剂平均大小为223.40±3.50nm，负载AA的弹性脂质体制剂平均大小为133.00±2.80nm。优化后的弹性脂质体制剂对TQ和AA的包封率（EE%）分别高达97.18±2.02%和93.08±1.95%。此外，边缘活化剂浓度对EE%有显著影响（P<0.05）；发现随着边缘活化剂（EA）用量增加，EE%升高。随后，将负载TQ和AA的最佳弹性脂质体制剂制成凝胶，并对其外观、pH值、铺展性、稳定性、流变学、体外释放、离体渗透研究和MTT细胞毒性进行了探究。所制备的弹性脂质体凝胶（R-1）pH值为5.53。此外，R-1凝胶的铺展性显著优于对照凝胶（P<0.05），并表现出剪切变稀行为。最重要的是，离体皮肤沉积研究证实了弹性脂质体凝胶中TQ和AA在皮肤中的沉积效果更佳。此外，结果表明酪氨酸酶抑制主要归因于TQ。单独比较TQ与TQ-AA组合时，抑制率分别为18.35%至42.73%和24.28%至42.53%。TQ弹性脂质体和TQ-AA组合均表现出对酪氨酸酶的浓度依赖性抑制。弹性脂质体凝胶可能是用于皮肤递送TQ和AA以治疗色素沉着过度病症的一种有前景的载体。
