Polyphenol-Based Nanoparticles Enhancing Doxycycline Efficacy for Acne Therapy

Abstract

Acne is an inflammatory dermatological disorder caused by Cutibacterium acnes (C. acnes), which primarily affects the face, neck, chest, and back, leading to skin impairment. This condition is often associated with post-inflammatory erythema, hyperpigmentation, scarring, as well as psychosocial and emotional distress. Based on the major pathological characteristics of acne with microbiome colonization, and multiple immune responses, we selected doxycycline, a clinically commonly used antibiotic and anti-inflammatory drug, and epigallocatechin gallate (EGCG), a polyphenol, to construct topical-applicable nanoparticles (NPs). The resulting doxycycline-EGCG (DE) NPs significantly reduced the proportion of dead cells in C. acnesinduced HaCaT cells and demonstrated excellent anti-inflammatory effects through inhibition of NF-κB and STAT3 pathways compared to doxycycline alone. Moreover, the DE NPs exhibited better enhanced antibacterial efficacy against C. acnes along with improved antioxidant capacity than doxycycline. In an acne-like mouse model, the DE NPs also effectively suppressed skin inflammation and reduced inflammatory cytokines expression. Overall, this work presents a co-assembly strategy driven by covalent and non-covalent interactions, affording polyphenol-based doxycycline NPs with potent antiinflammatory, antioxidant, antibacterial properties, and offering new opportunities for safe and effective acne local therapy.