Plant-based nanoparticle therapy eases skin thickening in SSc: Study
Experiments in mouse models also showed reduced inflammation
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A new nanoparticle-based delivery of kaempferol, a compound found in plants, vegetables, and herbs, reduced skin thickening, inflammation, and levels of molecules that induce fibrosis (scarring) in a mouse model of systemic sclerosis (SSc), according to a study.
Designed for delivery through the skin, the KLE treatment strategy combines two types of tiny fatty vesicles (natural exosomes and lab-made liposomes) loaded with kaempferol, allowing sustained drug release, improved skin retention, and multi-target anti-fibrotic effects. KLE stands for kaempferol-loaded liposome–exosome composite nanoparticle.
“This study systematically developed and validated a KLE for the topical treatment of skin fibrosis associated with systemic sclerosis,” researchers wrote. “KLE’s multi-target therapeutic efficacy, excellent biocompatibility [no harm or extended inflammation in the host], and sustained-release properties confirm its potential as a local nanotherapeutic strategy for systemic sclerosis-associated [skin] fibrosis.”
The study, “A bioengineered extracellular vesicle-based platform for targeted codelivery and multi-mechanistic therapy of skin fibrosis,” was published in the International Journal of Pharmaceutics.
Kaempferol has known anti-fibrotic, anti-inflammatory properties
SSc is characterized by thick and hardened skin caused by excessive production of collagen, a main component of scar tissue. Excessive scarring, or fibrosis, and other SSc-related changes can also occur in internal organs, including the heart, lungs, kidneys, and digestive tract.
Kaempferol has known anti-fibrotic, anti-inflammatory, and antioxidant properties. However, its clinical translation has been limited by poor water solubility, low skin permeability, and insufficient retention in fibrotic lesions. This, according to the investigators, has compromised its potential therapeutic efficacy.
To address these issues, researchers in China created the KLE therapy for transdermal (through the skin) administration.
According to the researchers, the tiny particles had adequate properties regarding skin adhesion and penetration, being stable without clumping and a uniform size.
Experiments using a mouse skin model showed that KLE led to sustained release of kaempferol through the skin. The formulation also showed good compatibility with fibroblasts (cells responsible for producing collagen) and blood.
This study demonstrates that KLE synergizes the high drug-loading capacity of liposomes and the delivery advantages of exosomes, serving as a safe and effective multi-target strategy for SSc-related skin fibrosis.
The researchers then tested the formulation in a mouse model of skin fibrosis. Over four weeks, the animals presented local redness and fluid accumulation at the injection site, and were less active relative to controls.
Mice received a KLE formulation on their back skin that incorporated glycerol to improve skin adhesion, prolong drug retention, and enable spreading in the affected skin. KLE treatment significantly reduced immune system activation and immune cell levels (consistent with anti-inflammatory activity), and effectively attenuated skin thickening and excessive collagen buildup. No relevant toxic effects to the liver or kidneys were detected.
At the molecular level, KLE significantly reduced the levels of the pro-inflammatory molecules TNF-alpha and IL-6. It also eased fibrotic signaling pathways, reducing the levels of TGF–beta1 and VEGF.
Further analysis revealed that KLE targeted several fibrosis-related pathways to confer its benefits.
“These predicted mechanisms of kaempferol provide a pharmacological basis for understanding the enhanced antifibrotic efficacy observed with the KLE delivery system, which improves local skin exposure and sustained drug availability, the researchers wrote. “TShis study demonstrates that KLE synergizes the high drug-loading capacity of liposomes and the delivery advantages of exosomes, serving as a safe and effective multi-target strategy for SSc-related skin fibrosis.”
