Innovative Solid Lipid Nanoparticle-Enriched Hydrogels for Enhanced Topical Delivery of L-Glutathione: A Novel Approach to Anti-Ageing

<b>Background:</b> 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 promi...

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Main Authors: Mengyang Liu, Manisha Sharma, Guoliang Lu, Zhiwen Zhang, Wenting Song, Jingyuan Wen
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/17/1/4
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author Mengyang Liu
Manisha Sharma
Guoliang Lu
Zhiwen Zhang
Wenting Song
Jingyuan Wen
author_facet Mengyang Liu
Manisha Sharma
Guoliang Lu
Zhiwen Zhang
Wenting Song
Jingyuan Wen
author_sort Mengyang Liu
collection DOAJ
description <b>Background:</b> 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. <b>Methods:</b> GSH-loaded SLNs were prepared via a double-emulsion technique and optimized using factorial design. These SLNs were incorporated into 1–3% (<i>w</i>/<i>v</i>) 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.
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spelling doaj-art-815100cc04b5433b91d3537bf9c94f6f2025-01-24T13:45:32ZengMDPI AGPharmaceutics1999-49232024-12-01171410.3390/pharmaceutics17010004Innovative Solid Lipid Nanoparticle-Enriched Hydrogels for Enhanced Topical Delivery of L-Glutathione: A Novel Approach to Anti-AgeingMengyang Liu0Manisha Sharma1Guoliang Lu2Zhiwen Zhang3Wenting Song4Jingyuan Wen5School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1023, New ZealandSchool of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1023, New ZealandAuckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New ZealandDepartment of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200433, ChinaDepartment of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, ChinaSchool of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1023, New Zealand<b>Background:</b> 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. <b>Methods:</b> GSH-loaded SLNs were prepared via a double-emulsion technique and optimized using factorial design. These SLNs were incorporated into 1–3% (<i>w</i>/<i>v</i>) 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.https://www.mdpi.com/1999-4923/17/1/4glutathioneantioxidanttopical deliveryhydrogelsolid lipid nanoparticlesanti-ageing
spellingShingle Mengyang Liu
Manisha Sharma
Guoliang Lu
Zhiwen Zhang
Wenting Song
Jingyuan Wen
Innovative Solid Lipid Nanoparticle-Enriched Hydrogels for Enhanced Topical Delivery of L-Glutathione: A Novel Approach to Anti-Ageing
Pharmaceutics
glutathione
antioxidant
topical delivery
hydrogel
solid lipid nanoparticles
anti-ageing
title Innovative Solid Lipid Nanoparticle-Enriched Hydrogels for Enhanced Topical Delivery of L-Glutathione: A Novel Approach to Anti-Ageing
title_full Innovative Solid Lipid Nanoparticle-Enriched Hydrogels for Enhanced Topical Delivery of L-Glutathione: A Novel Approach to Anti-Ageing
title_fullStr Innovative Solid Lipid Nanoparticle-Enriched Hydrogels for Enhanced Topical Delivery of L-Glutathione: A Novel Approach to Anti-Ageing
title_full_unstemmed Innovative Solid Lipid Nanoparticle-Enriched Hydrogels for Enhanced Topical Delivery of L-Glutathione: A Novel Approach to Anti-Ageing
title_short Innovative Solid Lipid Nanoparticle-Enriched Hydrogels for Enhanced Topical Delivery of L-Glutathione: A Novel Approach to Anti-Ageing
title_sort innovative solid lipid nanoparticle enriched hydrogels for enhanced topical delivery of l glutathione a novel approach to anti ageing
topic glutathione
antioxidant
topical delivery
hydrogel
solid lipid nanoparticles
anti-ageing
url https://www.mdpi.com/1999-4923/17/1/4
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