Improving the anti-keloid outcomes through liposomes loading paclitaxel-cholesterol complexes

Area of Science:

• Biomedical Engineering
• Dermatology
• Pharmacology

Background:

• Keloids are benign fibroproliferative tumors characterized by elevated inflammation and fibrosis.
• Paclitaxel (PTX) exhibits anti-fibrotic properties but faces clinical application challenges due to poor water solubility.
• Developing improved drug delivery systems is crucial for enhancing PTX efficacy in keloid treatment.

Purpose of the Study:

• To enhance the water solubility of Paclitaxel (PTX) through liposomal encapsulation.
• To investigate the anti-keloid effects of the developed PTX-cholesterol-loaded liposomes (PTXL) both in vitro and in vivo.
• To elucidate the underlying molecular mechanisms of PTX-mediated anti-fibrotic activity in keloid fibroblasts.

Main Methods:

• Preparation and physicochemical characterization of PTX-cholesterol-loaded liposomes (PTXL) using thin-film evaporation.
• In vitro assessment of PTXL's effects on human keloid fibroblast (HKF) proliferation, invasion, apoptosis, and cell cycle.
• In vivo evaluation of PTXL's efficacy in inhibiting keloid growth in a keloid-bearing mouse model.
• Analysis of PTX's impact on fibrogenic cytokine production (TNF-α, IL-6, TGF-β) and α-SMA, collagen I expression.
• Investigation of the role of the AKT/GSK3β signaling pathway in PTX-mediated anti-fibrotic effects.

Main Results:

• PTXL exhibited favorable physicochemical properties, including spherical morphology, optimal particle size (~101 nm), negative zeta potential (~-41 mV), high drug entrapment efficiency (~96%), and good stability.
• PTXL demonstrated enhanced in vitro efficacy compared to free PTX, effectively inhibiting HKF proliferation, migration, and invasion, while promoting apoptosis and G2/M cell cycle arrest.
• In vivo studies confirmed PTXL's superior performance in suppressing keloid growth in a mouse model.
• PTX treatment significantly suppressed pro-fibrotic factors (TNF-α, IL-6, TGF-β) and fibrotic markers (α-SMA, collagen I) by inhibiting the AKT/GSK3β signaling pathway.
• Inhibition of the PI3K/AKT pathway mimicked PTX's effects, confirming its role in ameliorating keloid fibrosis.

Conclusions:

• The developed PTX-cholesterol-loaded liposomes (PTXL) represent a promising strategy for improving PTX solubility and efficacy.
• PTXL exhibits significant anti-keloid properties by inhibiting fibroblast proliferation, invasion, and fibrosis through modulation of key signaling pathways.
• This novel liposomal formulation holds potential as a therapeutic agent for keloid treatment.