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Purpose <p>This study reports the <i>first statistically optimized dual-surfactant wintergreen oil nanoemulsion</i>, developed using a Box–Behnken design (BBD), that demonstrates enhanced antioxidant activity, stability, and topical permeation of methyl salicylate for dermal therapy. The research aimed to formulate and characterize a stable nanoemulsion system to improve the topical delivery efficiency and antioxidant performance of methyl salicylate.</p> Methods <p>The nanoemulsion was prepared using a high-speed homogenization–ultrasonication method, employing Tween 80 and sodium dodecyl sulfate (SDS) as surfactants. Critical formulation parameters affecting particle sizeand zeta potential were optimized using BBD. Comprehensive characterization included droplet size, polydispersity index (PDI), zeta potential, pH, viscosity, and stability under accelerated conditions. Antioxidant potential was evaluated through DPPH radical scavenging, permanganate assay, and superoxide dismutase (SOD) enzymatic assays, complemented by cellular ROS inhibition imaging. Ex vivo permeation was conducted using goat skin in a Franz diffusion system to validate improved diffusion behavior (Modi et al.in Braz J Pharm Sci. 2023;59:e01672, <CitationRef CitationID="CR1">2023</CitationRef>.</p> Results <p>The optimized nanoemulsion displayed a mean droplet size of 420&#xa0;nm, PDI 0.28, and zeta potential − 45 mV, evidencing strong colloidal stability. The formulation’s pH 5.5 was within the physiological skin range. In vitro release demonstrated a sustained 24-hour profile, whereas ex vivo results confirmed enhanced diffusion flux compared to the free oil. The nanoemulsion exhibited 56.7% DPPH radical scavenging and a 67.3% increase in SOD activity, indicating significant antioxidant efficacy. Fluorescence imaging further revealed decreased intracellular ROS accumulation. Stability analysis over three months confirmed minimal alterations in physicochemical parameters.</p> Conclusion <p>The developed BBD-optimized dual-surfactant wintergreen oil nanoemulsion offers an innovative, thermodynamically stable platform with improved antioxidant activity, skin permeability, and storage stability. Its synergistic surfactant system ensures enhanced topical bioavailability of methyl salicylate, highlighting its potential for antioxidant and anti-inflammatory dermatological applications. Future research should focus on in vivo efficacy and biochemical antioxidant evaluation (CAT, GPx, and MDA) for clinical translation.</p> Graphical Abstract <p></p>

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Formulation and Comprehensive Characterization of a Stable Wintergreen Oil Nano Emulsion with Enhanced Antioxidant Properties for Topical Delivery

  • 期刊论文

  • 发表日期：

    2025年12月29日

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  • Maccha Kiran Sai,
  • Bobbarjang Nagashubha,
  • Ramakrishna gari Pallavi,
  • Yellaboyala Roopeswari,
  • Golkonda Sameera Yasmin,
  • Bodanam Sainath,
  • Muthyalu Chakali,
  • Bandlapalli Charitha

摘要

Purpose

This study reports the first statistically optimized dual-surfactant wintergreen oil nanoemulsion, developed using a Box–Behnken design (BBD), that demonstrates enhanced antioxidant activity, stability, and topical permeation of methyl salicylate for dermal therapy. The research aimed to formulate and characterize a stable nanoemulsion system to improve the topical delivery efficiency and antioxidant performance of methyl salicylate.

Methods

The nanoemulsion was prepared using a high-speed homogenization–ultrasonication method, employing Tween 80 and sodium dodecyl sulfate (SDS) as surfactants. Critical formulation parameters affecting particle sizeand zeta potential were optimized using BBD. Comprehensive characterization included droplet size, polydispersity index (PDI), zeta potential, pH, viscosity, and stability under accelerated conditions. Antioxidant potential was evaluated through DPPH radical scavenging, permanganate assay, and superoxide dismutase (SOD) enzymatic assays, complemented by cellular ROS inhibition imaging. Ex vivo permeation was conducted using goat skin in a Franz diffusion system to validate improved diffusion behavior (Modi et al.in Braz J Pharm Sci. 2023;59:e01672, 2023.

Results

The optimized nanoemulsion displayed a mean droplet size of 420 nm, PDI 0.28, and zeta potential − 45 mV, evidencing strong colloidal stability. The formulation’s pH 5.5 was within the physiological skin range. In vitro release demonstrated a sustained 24-hour profile, whereas ex vivo results confirmed enhanced diffusion flux compared to the free oil. The nanoemulsion exhibited 56.7% DPPH radical scavenging and a 67.3% increase in SOD activity, indicating significant antioxidant efficacy. Fluorescence imaging further revealed decreased intracellular ROS accumulation. Stability analysis over three months confirmed minimal alterations in physicochemical parameters.

Conclusion

The developed BBD-optimized dual-surfactant wintergreen oil nanoemulsion offers an innovative, thermodynamically stable platform with improved antioxidant activity, skin permeability, and storage stability. Its synergistic surfactant system ensures enhanced topical bioavailability of methyl salicylate, highlighting its potential for antioxidant and anti-inflammatory dermatological applications. Future research should focus on in vivo efficacy and biochemical antioxidant evaluation (CAT, GPx, and MDA) for clinical translation.

Graphical Abstract