Human Skin Permeation Studies with PPARγ Agonist to Improve Its Permeability and Efficacy in Inflammatory Processes

Abstract

Rosacea is the most common inflammatory skin disease. It is characterized by erythema, inflammatory papules and pustules, visible blood vessels, and telangiectasia. The current treatment has limitations and unsatisfactory results. Pioglitazone (PGZ) is an agonist of peroxisome proliferator-activated receptors (PPARs), a nuclear receptor that regulates important cellular functions, including inflammatory responses. The purpose of this study was to evaluate the permeation of PGZ with a selection of penetration enhancers and to analyze its effectiveness for treating rosacea. The high-performance liquid chromatography (HPLC) method was validated for the quantitative determination of PGZ. Ex vivo permeation experiments were realized in Franz diffusion cells using human skin, in which PGZ with different penetration enhancers were assayed. The results showed that the limonene was the most effective penetration enhancer that promotes the permeation of PGZ through the skin. The cytotoxicity studies and the Draize test detected cell viability and the absence of skin irritation, respectively. The determination of the skin color using a skin colorimetric probe and the results of histopathological studies confirmed the ability of PGZ-limonene to reduce erythema and vasodilation. This study suggests new pharmacological indications of PGZ and its possible application in the treatment of skin diseases, namely rosacea.

Development of Pranoprofen Loaded Nanostructured Lipid Carriers to Improve Its Release and Therapeutic Efficacy in Skin Inflammatory Disorders

“…The EE, Z-Ave, and PI could be maintained without significant changes over a storage period of 60 days at 25 °C and 180 days at 4 °C. However, in the case of storage at 37 °C, changes were evident within 15 days.The release profile of the drug from the vehicle is important information that can be used to predict in vivo behavior [41]. As expected for nanostructured lipid carriers, a slow and sustained release profile for optimized NLCs was observed, explained by the solid matrix of this nanostructure and the subsequent drug immobilization.…”

Nanoparticle-mediated local delivery of pioglitazone attenuates bleomycin-induced skin fibrosis

“…However, systemic administration of thiazolidinediones is associated with fluid retention, which sometimes leads to congestive heart failure [21] and has a hypoglycemic effect. To avoid these systemic reactions, the topical use of pioglitazone with penetration enhancers has been investigated [22]; however, because of the hydrophobic property of pioglitazone, it is difficult to target the dermal layer through topical application and local injection.…”

Comparative Study of Ex Vivo Transmucosal Permeation of Pioglitazone Nanoparticles for the Treatment of Alzheimer’s Disease

“…The non-entrapped PGZ was separated using filtration/centrifugation (1:10 dilution) with Ultracell–100 K (Amicon ® Ultra; Millipore Corporation, Billerica, MA, USA) centrifugal filter devices at 12,000 rpm for 15 min. PGZ was measured using a previously validated high performance liquid chromatographic (HPLC) method [15]. EE(%)=Total amount of PGZ − Free amount of PGZTotal amount of PGZ·100…”