Liu Mengyang, Sharma Manisha, Lu Guoliang, Zhang Zhiwen, Song Wenting, Wen Jingyuan
School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1023, New Zealand.
Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand.
Pharmaceutics. 2024 Dec 24;17(1):4. doi: 10.3390/pharmaceutics17010004.
Skin ageing, driven predominantly by oxidative stress from reactive oxygen species (ROS) induced by environmental factors like ultraviolet A (UVA) radiation, accounts for approximately 80% of extrinsic skin damage. L-glutathione (GSH), a potent antioxidant, holds promise in combating UVA-induced oxidative stress. However, its instability and limited penetration through the stratum corneum hinder its topical application. This study introduces a novel solid lipid nanoparticle (SLN)-enriched hydrogel designed to enhance GSH stability, skin penetration, and sustained release for anti-ageing applications. GSH-loaded SLNs were prepared via a double-emulsion technique and optimized using factorial design. These SLNs were incorporated into 1-3% (/) Carbopol hydrogels to produce a semi-solid formulation. The hydrogel's characteristics, including morphology, mechanical and rheological properties, drug release, stability, antioxidant activity, cytotoxicity, and skin penetration, were evaluated. SEM and FTIR confirmed the uniform dispersion of SLNs within the hydrogel. The formulation exhibited desirable properties, including gel strength (5.1 ± 0.5 g), spreadability (33.6 ± 1.9 g·s), pseudoplasticity, and elasticity. In vitro studies revealed a biphasic GSH release profile, with sustained release over 72 h and over 70% cumulative release. The hydrogel significantly improved antioxidant capacity, protecting human fibroblasts from UVA-induced oxidative stress and enhancing cell viability. Stability studies indicated that 4 °C was optimal for storage over three months. Notably, the hydrogel enhanced GSH penetration through the stratum corneum by 3.7-fold. This SLN-enriched hydrogel effectively improves GSH topical delivery and antioxidant efficacy, providing a promising platform for anti-ageing and other bioactive compounds with similar delivery challenges.
皮肤老化主要由环境因素如紫外线A（UVA）辐射诱导的活性氧（ROS）产生的氧化应激所驱动，约占外在皮肤损伤的80%。L-谷胱甘肽（GSH）是一种强效抗氧化剂，有望对抗UVA诱导的氧化应激。然而，其不稳定性以及通过角质层的渗透有限阻碍了其局部应用。本研究引入了一种新型的富含固体脂质纳米颗粒（SLN）的水凝胶，旨在提高GSH的稳定性、皮肤渗透性和持续释放，用于抗老化应用。通过双乳液技术制备了负载GSH的SLN，并使用析因设计进行优化。将这些SLN掺入1 - 3%（/）的卡波姆水凝胶中制成半固体制剂。评估了水凝胶的特性，包括形态、机械和流变学性质、药物释放、稳定性、抗氧化活性、细胞毒性和皮肤渗透性。扫描电子显微镜（SEM）和傅里叶变换红外光谱（FTIR）证实了SLN在水凝胶中的均匀分散。该制剂表现出理想的性质，包括凝胶强度（5.1±0.5 g）、铺展性（33.6±1.9 g·s）、假塑性和弹性。体外研究显示GSH呈双相释放曲线，在72小时内持续释放，累积释放超过70%。该水凝胶显著提高了抗氧化能力，保护人成纤维细胞免受UVA诱导的氧化应激并提高细胞活力。稳定性研究表明，4℃是三个月以上储存的最佳温度。值得注意的是，该水凝胶使GSH透过角质层的渗透率提高了3.7倍。这种富含SLN的水凝胶有效改善了GSH的局部递送和抗氧化功效，为抗老化及其他具有类似递送挑战的生物活性化合物提供了一个有前景的平台。
