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Abstract <p>Chronic wounds represent a major clinical challenge due to persistent inflammation, oxidative stress, microbial colonization, and impaired angiogenesis, necessitating multifunctional therapeutic strategies. This study reports the Quality-by-Design (QbD)-driven development and optimization of curcumin–quercetin co-loaded nanoliposomes (CQL) for advanced wound healing applications. Preformulation studies confirmed the physicochemical suitability and drug–excipient compatibility of both phytoconstituents. Liposomes were prepared using the alcohol injection method and systematically optimized through a Taguchi screening design followed by a three-factor, three-level Box–Behnken design. Phosphatidylcholine concentration, processing temperature, and ethanol percentage were identified as critical variables governing particle size, entrapment efficiency, and zeta potential. Quadratic modeling and desirability analysis yielded an optimized formulation exhibiting nanoscale particle size (~ 76&#xa0;nm), high entrapment efficiency (~ 92%), and stable surface charge (≈ − 18 to − 28&#xa0;mV), demonstrating excellent model predictability and robustness. Scanning electron microscopy confirmed spherical morphology and uniform nanoscale distribution. Biological evaluation revealed good hemocompatibility (&lt; 5% hemolysis), absence of erythrocyte aggregation, and concentration-dependent antibacterial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans. <i>In-vitro</i> and <i>in-vivo</i> bioassay demonstrated significantly enhanced wound closure with the treatment of liposomal formulation. This healing potential of liposomal treatment also reverses the increased level of inflammatory cytokines (IL-6, IL-1β, TNF-α, and IL-10) and oxidative stress markers (MDA and SOD) in burn injury. Collectively, the optimized nanoliposomal system provides a scalable and translational platform capable of simultaneous antimicrobial, anti-inflammatory, and regenerative modulation, supporting its integration into advanced wound care scaffolds and localized therapeutic systems.</p> Lay Summary <p>This study developed tiny lipid-based carriers to deliver natural compounds curcumin and quercetin for improved wound healing. The optimized formulation showed good safety, antibacterial effects, and faster wound closure, offering a promising advanced treatment option for chronic wounds.</p>

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Quality-by-Design–Driven Development, Optimization, and Toxicological Evaluation of Curcumin–Quercetin Co-loaded Nanoliposomal Formulations for Anti-microbial and Wound Healing Effects

  • 期刊论文

  • 发表日期：

    2026年6月30日

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  • Lovekesh Nagpal,
  • Saahil Arora

摘要

Abstract

Chronic wounds represent a major clinical challenge due to persistent inflammation, oxidative stress, microbial colonization, and impaired angiogenesis, necessitating multifunctional therapeutic strategies. This study reports the Quality-by-Design (QbD)-driven development and optimization of curcumin–quercetin co-loaded nanoliposomes (CQL) for advanced wound healing applications. Preformulation studies confirmed the physicochemical suitability and drug–excipient compatibility of both phytoconstituents. Liposomes were prepared using the alcohol injection method and systematically optimized through a Taguchi screening design followed by a three-factor, three-level Box–Behnken design. Phosphatidylcholine concentration, processing temperature, and ethanol percentage were identified as critical variables governing particle size, entrapment efficiency, and zeta potential. Quadratic modeling and desirability analysis yielded an optimized formulation exhibiting nanoscale particle size (~ 76 nm), high entrapment efficiency (~ 92%), and stable surface charge (≈ − 18 to − 28 mV), demonstrating excellent model predictability and robustness. Scanning electron microscopy confirmed spherical morphology and uniform nanoscale distribution. Biological evaluation revealed good hemocompatibility (< 5% hemolysis), absence of erythrocyte aggregation, and concentration-dependent antibacterial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans. In-vitro and in-vivo bioassay demonstrated significantly enhanced wound closure with the treatment of liposomal formulation. This healing potential of liposomal treatment also reverses the increased level of inflammatory cytokines (IL-6, IL-1β, TNF-α, and IL-10) and oxidative stress markers (MDA and SOD) in burn injury. Collectively, the optimized nanoliposomal system provides a scalable and translational platform capable of simultaneous antimicrobial, anti-inflammatory, and regenerative modulation, supporting its integration into advanced wound care scaffolds and localized therapeutic systems.

Lay Summary

This study developed tiny lipid-based carriers to deliver natural compounds curcumin and quercetin for improved wound healing. The optimized formulation showed good safety, antibacterial effects, and faster wound closure, offering a promising advanced treatment option for chronic wounds.