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

Q: What is the goal of the Quality-by-Design (QbD) study?

To develop and optimize curcumin–quercetin co-loaded nanoliposomal formulations for advanced wound healing applications, while targeting antimicrobial and anti-inflammatory effects.

Q: How was the optimized formulation evaluated biologically?

Biological evaluation included hemocompatibility, antibacterial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans, and wound closure enhancement in in-vitro and in-vivo bioassays, including burn-injury inflammatory and oxidative stress markers.

Aug 28, 2026

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Chronic wounds are driven by persistent inflammation, oxidative stress, microbial colonization, and impaired angiogenesis, requiring multifunctional therapeutics. This study presents a Quality-by-Design (QbD) workflow to develop and optimize curcumin–quercetin co-loaded nanoliposomes for wound healing. Preformulation confirmed suitability and compatibility. Alcohol injection liposomes were optimized using Taguchi screening and a Box–Behnken design, identifying phosphatidylcholine concentration, temperature, and ethanol as critical variables.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Abstract

Lay Summary

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Introduction

Regenerative Engineering and Translational Medicine [https://doi.org/10.1007/s40883-026-00614-1](https://doi.org/10.1007/s40883-026-00614-1) ORIGINAL RESEARCH Quality-by-Design–Driven Development, Optimization, and Toxicological Evaluation of Curcumin–Quercetin Co-loaded Nanoliposomal Formulations for Anti-microbial and Wound Healing Effects Lovekesh Nagpal1 · Saahil Arora1 Received: 21 February 2026 / Revised: 25 May 2026 / Accepted: 14 June 2026 © The Author(s), under exclusive licence to The Regenerative Engineering Society 2026 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-byDesign (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. Keywords Curcumin · Quercetin · Nanoliposomes · Quality-by-Design (QbD) · Wound Healing · Box–Behnken Design Introduction Wound healing is a complex, multistage biological process involving haemostasis, inflammation, proliferation, 􀀍 Lovekesh Nagpal [lovekeshnagpal@aol.com](lovekeshnagpal@aol.com); [lovely29jan@gmail.com](lovely29jan@gmail.com) Saahil Arora [saahil70@gmail.com](saahil70@gmail.com) 1 School of Healthcare and Allied Sciences, G.D Goenka University, Sohna, Gurugram, Haryana, India and tissue remodeling [1, 2] . While acute wounds typically resolve in an orderly and time-dependent manner, chronic wounds fail to progress through these phases, resulting in persistent tissue damage [3, 4]. The global burden ofchronic wounds including diabetic foot ulcers, pressure injuries, and venous leg ulcers continues to rise due to increasing prevalence of diabetes, vascular insufficiency, aging, and immune dysregulation [5, 6] . Clinically, wound chronicity is associated with sustained inflammation, oxidative stress, microbial colo

FAQs

What is the goal of the Quality-by-Design (QbD) study?

To develop and optimize curcumin–quercetin co-loaded nanoliposomal formulations for advanced wound healing applications, while targeting antimicrobial and anti-inflammatory effects.

Which formulation parameters were identified as critical in the optimization?

Phosphatidylcholine concentration, processing temperature, and ethanol percentage were identified as critical variables affecting particle size, entrapment efficiency, and zeta potential.

How was the optimized formulation evaluated biologically?

Biological evaluation included hemocompatibility, antibacterial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans, and wound closure enhancement in in-vitro and in-vivo bioassays, including burn-injury inflammatory and oxidative stress markers.

Aug 28, 2026

Upload by Sage