Novel Pullulan/Gellan Gum Bilayer Film as a Vehicle for Silibinin-Loaded Nanocapsules in the Topical Treatment of Atopic Dermatitis.

In this study a novel gellan gum/pullulan bilayer film containing silibinin-loaded nanocapsules was developed for topical treatment of atopic dermatitis (AD). The bilayer films were produced by applying a pullulan layer on a gellan gum layer incorporated with silibinin nanocapsules by two-step solvent casting method. The bilayer formation was confirmed by microscopic analysis. In vitro studies showed that pullulan imparts bioadhesitvity for the films and the presence of nanocapsules increased their occlusion factor almost 2-fold. Besides, the nano-based film presented a slow silibinin release and high affinity for cutaneous tissue. Moreover, this film presented high scavenger capacity and non-hemolytic property. In the in vivo study, interestingly, the treatments with vehicle film attenuated the scratching behavior and the ear edema in mice induced by 2,4-dinitrochlorobenzene (DNCB). However, the nano-based film containing silibinin modulated the inflammatory and oxidative parameters in a similar or more pronounced way than silibinin solution and vehicle film, as well as than hydrocortisone, a classical treatment of AD. In conclusion, these data suggest that itself gellan gum/pullulan bilayer film might attenuate the effects induced by DNCB, acting together with silibinin-loaded nanocapsules, which protected the skin from oxidative damage, improving the therapeutic effect in this AD-model.

Incorporation of nanocapsules into gellan gum films: A strategy to improve the stability and prolong the cutaneous release of silibinin.

This study aimed to develop gellan gum films containing silibinin-loaded nanocapsules as a novel approach for cutaneous administration of this flavonoid. The nanocapsule suspensions were prepared and presented mean size around 140 nm with homogenous distribution, negative zeta potential and silibinin encapsulation efficiency close to 100%. Then, these suspensions were converted into gellan gum films by solvent casting method. The films were transparent, flexible and maintained the gellan gum hydrophilicity. Nanocapsules provided the silibinin homogenous distribution in the films and prolonged its release, as well as improved the gellan gum occlusion potential. Besides, the nanosuspensions conversion into films improved the silibinin stability. Additionally, the nano-based films presented a swelling index 1.5 times higher than films containing non-nanoencapsulated silibinin. Microscopic analysis evidenced the homogeneous surface of the nano-based films, while films containing non-nanoencapsulated silibinin presented small cracks. The in vitro skin permeation profile confirmed the silibinin gradual release from the nano-based films and its greater retention in the dermis when the skin is damaged. Finally, the formulations presented no irritant effect in the HET-CAM assay. Therefore, the conversion of silibinin-loaded nanocapsule suspensions into films might be considered a promising platform for skin delivery of this flavonoid.