Development and evaluation of nanostructured systems for cutaneous delivery of H2S-releasing corticosteroids for skin inflammatory diseases.

Psoriasis is an immune-mediated chronic inflammatory disease that causes major psychosocial impact. Topical corticosteroids represent the standard pharmacological treatment for mild-to-moderate disease, but their local and systemic adverse effects reinforce the need for treatment innovations. Here we developed lamellar phase-based formulations for topical delivery of a hybrid dexamethasone and hydrogen sulfide (H2S) donor molecule (Dexa-TBZ), aiming to potentiate the effects of the glucocorticoid with H2S. They offer the possibility to obtain precursor formulations free of water that originate lamellar phases upon water addition, preventing drug hydrolysis during storage. Two groups of formulations were developed varying the surfactants and oil phase types and content. Systems containing 20 and 70 % of water formed, respectively, bulk lamellar phase and a more fluid formulation consisting of dispersed droplets (< 1000 nm) stabilized by lamellar phase. Both presented pseudoplastic behavior. Dexa-TBZ was incorporated at 1 %, remaining stable for 8 h. Drug content decreased to ∼80 % after 1 week in precursor formulations free of water, but remained stable after that. Without causing changes to the cutaneous barrier function ex vivo or to the histological structure of the skin in vivo, the formulation containing phosphatidylcholine as surfactant and 70 % of water promoted 1.8- and 2.7-fold increases in Dexa-TBZ penetration in the stratum corneum and epidermis+dermis, respectively, compared to a control solution, demonstrating their potential applicability as topical delivery systems.

Preclinical study of methotrexate-based hydrogels versus surfactant based liquid crystal systems on psoriasis treatment.

Psoriasis is an autoimmune, inflammatory and chronic skin disease in which cell growth and proliferation are increased, causing erythema, lesions and skin's peeling. Oral methotrexate (MTX) is the first-choice drug when phototherapy or retinoid treatment are not effective. Topical administration can be advantageous to better orientate the drug's delivery; however, the stratum corneum performs as a barrier for hydrofilic drugs penetration. This study sought to evaluate two different types of vehicles for MTX on the psoriasis treatment - hydrogel and liquid crystal systems (LCs). Lamellar and hexagonal liquid crystalline phases were selected from a ternary phase diagram based on polysorbate 80, isopropyl miristate and water. The hydrogel was based on alkylated carbomer (ACH). Rheological analysis showed ACH was more elastic than lamellar and hexagonal phases. ACH interacted better with pig skin than LCs in bioadhesion assay. Preclinical study revealed the ACH decreased inflammation in mice with induced psoriasis, being as effective as dexamethasone to regulate epidermis thickness, COX-2 and myeloperoxidase activity and TNF-α level, while LCs demonstrated inflammatory effect. Therefore, MTX-loaded hydrogel based platforms are indicated for local treatment of psoriasis and present great potential for further studies.

Inclusion of Laponite nanoparticles in a lyotropic lamellar phase.

In this work, we consider a ternary system formed by a surfactant with a lamellar phase (lecithin) that was doped with a solution of Laponite at 1% by volume. The inclusion of nanoparticles in the lamellar phase was investigated by the small-angle X-ray scattering (SAXS) technique, which revealed three types of structures according to the observed scattering pattern. The lamellar period increased linearly with hydration up to a certain limit; this type of behavior is not the same as that found for a similar system using AOT as a surfactant. In the region that corresponds to an isotropic phase, it was observed that the period corresponds to 60 Å, and in the lamellar system of pure lecithin, with the same volumetric fraction (1/φ = 0.66), the corresponding periodicity is 62 Å, indicating that the presence of Laponite nanoparticles increases the attractive interaction, reducing the lamellar period, causing the bilayer to become more rigid, that is, with less fluctuations. In the more diluted region, the periodicity reached a limit value of 64 Å, which is slightly higher than the lamellar system in the absence of Laponite particles, so there was an expansion of the lamellar phase due to the lack of consistency of Laponite nanoparticles. In the more concentrated lamellar phase (under strong confinement), it was observed that the distance between the bilayers decreased, establishing a long-range order.