Rational Design of Lecithin–Cholesterol Liposomes for Encapsulation and Sustained Release of Diclofenac

Liposomes are widely recognized as versatile nanocarriers in drug delivery due to their biocompatibility, tunable physicochemical properties, and ability to incorporate both hydrophilic and hydrophobic compounds. In this study, the encapsulation and release of diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), using lecithin–cholesterol liposomes are explored. Encapsulation parameters were first optimized with calcein as a model fluorophore, confirming that cholesterol addition enhances encapsulation efficiency by reducing membrane permeability. Guided by these results, liposomes containing equal weight fractions of lecithin and cholesterol were selected as an optimized formulation, providing calcein and diclofenac encapsulation efficiencies up to approximately 35% while maintaining hydrodynamic diameters below 300 nm with low polydispersity (PdI < 0.2), optimal for intravenous administration and prolonged systemic circulation. Release studies demonstrated sustained drug release over 15 days, with cumulative release exceeding 80%. Weibull modeling yielded θ∞ ≈ 1 and β values up to ~1.6 at higher loadings, with β > 1 indicating a complex, sigmoidal (non-Fickian) release mechanism. These findings support the potential of liposomes as delivery platforms for NSAIDs with solubility and bioavailability limitations.