Optimization of Liposomal Eye Drops Co-Loaded with Triamcinolone Acetonide and Folic Acid for Retinal Vascular Disorders

Background

Diabetic Retinopathy (DR) and Diabetic Macular Edema (DME) require effective posterior segment drug delivery, challenged by ocular anatomical barriers. Triamcinolone Acetonide (TA) despite its intravitreal efficacy carries risks of elevated intraocular pressure and cataract formation. Folic Acid (FA) exhibits anti-angiogenic and anti-oxidant potential but suffers poor corneal permeability. Co-loaded liposomal systems offer a non-invasive strategy by encapsulating both hydrophilic and lipophilic drugs enhancing therapeutic outcomes.

Materials and Methods

Liposomes were prepared by thin-film hydration method and optimized by 2³ full factorial design, by varying L-α Phosphatidylcholine, cholesterol, and dicetyl phosphate concentrations with vesicle size, Zeta potential and Entrapment Efficiency (EE) as responses. The optimized formulation was characterized for physicochemical properties (pH, viscosity, Density, Surface tension and osmolarity), SEM morphology, in vitro release and its kinetics, anti-inflammatory activity, ex vivo permeation and 90-day stability assessment.

Results

The optimized formulation F9 exhibited 206 nm vesicle size, PDI of 0.145, zeta potential of -32.35 mV, and EE of 69.21±3.2% for TA and 78.6±1.4% for FA. Physicochemical evaluation confirmed stability. In vitro Release demonstrated enhanced release of TA (98.5±2.5%) and FA (96.4±1.3%) over 8 hr compared to plain TAFA via zero-order, non-Fickian kinetics. Ex vivo Permeation was significantly greater than plain TAFA solutions. Anti-inflammatory inhibition reached 90.1±2.1% with strong IVEVC correlations (R²>0.997).

Conclusion

This novel liposomal formulation of TA and FA represents a clinically viable, non-invasive topical alternative to intravitreal injections for DR and DME management.