Hyaluronic acid–functionalized lipid nanocarrier system for enhanced anti-inflammatory delivery of ibuprofen: Formulation, optimization, and in vivo evaluation

Document Type

Article

Publication Date

Spring 5-19-2026

Abstract

Ibuprofen (IBU) is a widely used anti-inflammatory drug, yet its topical effectiveness is limited by poor transdermal permeation. This study aimed to enhance IBU delivery and biological activity through a novel system integrating hyaluronic acid (HA), lipid-based nanocarriers (LNC), and an emulgel base. The objective was to optimize IBU-loaded LNC, apply HA surface functionalization, and evaluate the resulting formulation in vitro and in vivo. A 23 factorial design was used to investigate the effects of lipid type, lipid concentration, and Tween 80 concentration on particle size, zeta potential, and entrapment efficiency. Formulations were prepared using hot homogenization followed by ultrasonication. The optimized LNC was coated with HA and incorporated into an emulgel matrix. Anti-inflammatory activity was assessed in vitro using membrane stabilization and lipoxygenase inhibition assays, while in vivo evaluation was conducted using the carrageenan-induced rat paw edema model. The optimized formulation demonstrated a particle size of 325 ± 6.2 nm, PDI of 0.301 ± 0.04, zeta potential of −29 ± 2.1 mV, entrapment efficiency of 79 ± 2.8%, and drug release of 86 ± 3.1%. In vitro assays showed that HA-IBU-LNC exhibited a significantly lower IC50 for membrane stabilization (25.6 ± 1.8 μg/mL vs. 39.9 ± 2.1 μg/mL for free IBU) and for lipoxygenase inhibition (3.7 ± 0.3 μg/mL vs. 6.3 ± 0.6 μg/mL for free IBU). In vivo, the HA-coated IBU-LNC emulgel significantly reduced paw edema, achieving a superior inhibition of 72.7 ± 6.4% compared to 33.45 ± 8.91% for IBU-LNC emulgel, and 9.82 ± 7.9% for the conventional IBU gel, findings further supported by histological improvement. The HA-functionalized IBU-LNC emulgel enhanced transdermal delivery and anti-inflammatory efficacy, demonstrating clear advantages over standard IBU gel and supporting its potential as an advanced topical therapy for inflammation.

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