Silymarin loaded hyaluronic acid-coated cubosomal gel for topical delivery: Optimization, characterizations, and ex vivo skin permeation studies.

Objective

This study aimed to develop a silymarin (SLM) loaded cubosomal gel and coat it with hyaluronic acid on the surface of the optimized formulation to evaluate skin permeation efficiency.

Methods

The cubosomes (CBS) was prepared using a top-down method with monoolein, poloxamer 407, and sonication. A Box-Behnken design was employed to optimize the CBS based on the particle size, entrapment efficiency (%EE), and cumulative drug release (%CDR). The optimized CBS were coated with 0.2% and 0.4% hyaluronic acid (HA) and incorporated into Carbopol 940 gel. Ex vivo permeation studies of the cubosomal gel were performed using goat ear skin to evaluate skin permeation and drug retention of SLM.

Results

The optimized CBS showed a particle size of 233 ± 7.8 nm, zeta potential of -22.6 ± 0.5 mV, % EE of 82.7 ± 2.6%, and %CDR of 91.7 ± 3.5%. The uncoated SLM cubosomal gel showed higher permeability (0.87 × 10-6 cm/s) than the plain SLM gel (0.28 × 10-6 cm/s). HA coating further enhanced permeation, with the 0.2% HA and 0.4% HA coated cubosomal gels exhibiting a permeability coefficients of 1.15 × 10-6 cm/s and 1.26 × 10-6 cm/s, respectively. The 0.4% HA-coated cubosomal gel showed a 1.45-fold increase in permeability compared to the uncoated cubosomal gel. Furthermore, HA coating significantly enhanced drug retention (p < 0.05) compared to that of the uncoated cubosomal gel.

Conclusion

The 0.4% HA-coated cubosomal gel demonstrated the highest permeability coefficient, indicating its potential for enhanced topical delivery of SLM.