Purpose: Acne vulgaris is a chronic inflammatory skin disorder centered on hair follicles, making hair follicle-targeted delivery of anti-acne drugs a promising option for acne treatment. However, current researches have only focused on the delivering to healthy hair follicles, which are intrinsically different from pathologically clogged hair follicles in acne vulgaris. Patients and Methods: Azelaic acid (AZA) micro/nanocrystals with different particle sizes were prepared by wet media milling or high-pressure homogenization. An experiment on AZA micro/nanocrystals delivering to healthy hair follicles was carried out, with and without the use of physical enhancement techniques. More importantly, it innovatively designed an experiment, which could reveal the ability of AZA micro/nanocrystals to penetrate the constructed clogged hair follicles. The anti-inflammatory and antibacterial effects of AZA micro/nanocrystals were evaluated in vitro using a RAW264.7 cell model stimulated by lipopolysaccharide and a Cutibacterium acnes model. Finally, both the anti-acne effects and skin safety of AZA micro/nanocrystals and commercial products were compared in vivo. Results: In comparison to commercial products, 200 nm and 500 nm AZA micro/nanocrystals exhibited an increased capacity to target hair follicles. In the combination group of AZA micro/nanocrystals and ultrasound, the ability to penetrate hair follicles was further remarkably enhanced (ER value up to 9.6). However, toward the clogged hair follicles, AZA micro/nanocrystals cannot easily penetrate into by themselves. Only with the help of 1% salicylic acid, AZA micro/nanocrystals had a great potential to penetrate clogged hair follicle. It was also shown that AZA micro/nanocrystals had anti-inflammatory and antibacterial effects by inhibiting pro-inflammatory factors and Cutibacterium acnes. Compared with commercial products, the combination of AZA micro/nanocrystals and ultrasound exhibited an obvious advantage in both skin safety and in vivo anti-acne therapeutic efficacy. Conclusion: Hair follicle-targeted delivery of AZA micro/nanocrystals provided a satisfactory alternative in promoting the treatment of acne vulgaris.

Background: 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. Methods: GSH-loaded SLNs were prepared via a double-emulsion technique and optimized using factorial design. These SLNs were incorporated into 1–3% (w/v) 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. Results: 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. Conclusions: 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.