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Optimization and Characterization of Adenosine-Loaded Nanoemulsion for Enhanced Stability and Controlled Drug Release

Nuttamon Thaicharoen, Kullanan Paeyai, Sukanya Thepwatee, Lida Simasatitkul, Samitthichai Seeyangnok, Nisalak Trongsiriwat, Itthipol Sungwienwong

Abstract


Adenosine is a bioactive compound widely used in pharmaceutical and cosmetic applications due to its anti-inflammatory, wound-healing, and anti-aging properties. However, its formulation remains challenging because of its limited physicochemical stability and delivery efficiency in conventional systems. Nanoemulsions have emerged as promising delivery vehicles capable of enhancing the stability, bioavailability, and controlled release of bioactive compounds. Therefore, this study systematically investigates the influence of surfactant systems and oil phase composition on the physicochemical properties, stability, and release kinetics of adenosine-loaded nanoemulsions. Nanoemulsions were formulated using Tween 80 and Span 80 with varying hydrophilic–lipophilic balance (HLB) values and different oil phases via a low-energy emulsification method. The optimized formulation (HLB 12.86, jojoba oil) exhibited a mean droplet size of 215.7 ± 1.1 nm, polydispersity index (PDI) of 0.434, zeta potential of −54.0 ± 0.6 mV with encapsulation efficiency (%EE) of 54.7 and drug loading (%DL) of 2.8, indicating good colloidal stability. Stability studies revealed that the nanoemulsion remained stable under ambient conditions but was sensitive to temperature cycling and pH variations. In vitro release studies demonstrated a diffusion-controlled release mechanism best described by the Higuchi model (R² = 0.842), while the Korsmeyer–Peppas model (n = 0.638) indicated anomalous transport behavior. Cytotoxicity evaluation on Vero cells confirmed acceptable biocompatibility, with improved cell viability compared to free adenosine (IC50 > 100 µg/mL). Overall, this study highlights the critical role of surfactant–oil interactions in modulating nanoemulsion stability and drug release, providing insights for the rational design of delivery systems for bioactive compounds.

Keywords



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DOI: 10.14416/j.asep.2026.08.009

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