Development and Optimization of Puerarin-loaded Proniosomal gel for topical ocular delivery: an in vitro and ex vivo...

The present study aimed to develop and optimize puerarin-loaded proniosomal gel for topical ocular delivery in dry eye disease (DED), overcoming poor corneal permeability, rapid precorneal elimination, and frequent dosing limitations of conventional ophthalmic formulations.

Proniosomal gels were prepared using Span 60, cholesterol, Gelucire 44/14, lecithin and Carbopol 974P by coacervation-phase separation method. A three-factor Box-Behnken design (BBD) was employed to optimize three independent variables amount of Span 60 (X1), cholesterol (X2), and Gelucire 44/14 (X3) with entrapment efficiency (EE%) and vesicle size as dependent responses. The goal of the proposed formulation was to achieve maximum EE% and minimum vesicle size as critical quality attributes (CQAs). EE%, vesicle size, PDI, zeta potential, pH, viscosity and drug content were characterized for all formulations. Freshly excised goat corneas were used for the ex vivo transcorneal permeation, while physicochemical stability was assessed during six months according to ICH Q1A(R2) guidelines.

The Batch PF17 was optimized based upon desirability score of 1.0 showed EE% 81.62 ± 1.14%, vesicle size 248.4 ± 6.18 nm, PDI of 0.288 ± 0.013, zeta potential - 33.2 ± 1.62 mV and drug content 99.24 ± 0.68%. PF17 showed highest transcorneal flux of 220.13 ± 5.24 μg/cm²/h and a permeation enhancement ratio of 3.29 compared to plain puerarin eye drops. Stability studies indicated a reduction of EE% of less than 2.99% under accelerated condition for six months and within the acceptable limit.

Puerarin-loaded proniosomal gel is a promising, stable ocular drug delivery platform demonstrating enhanced ex vivo transcorneal permeation relevant to sustained management of DED. As the present findings are limited to in vitro and ex vivo evaluation, ocular bioavailability was not directly assessed and requires confirmation through future in vivo pharmacokinetic, corneal retention, and biodistribution studies before clinical translation can be established.