brij-58 and idebenone

Idebenone (IDE), a synthetic derivative of ubiquinone, shows a potent antioxidant activity that could be beneficial in the treatment of skin oxidative damages. In this work, the feasibility of targeting IDE into the upper layers of the skin by topical application of IDE-loaded solid lipid nanoparticles (SLN) was evaluated. SLN loading different amounts of IDE were prepared by the phase inversion temperature method using cetyl palmitate as solid lipid and three different non-ionic surfactants: ceteth-20, isoceteth-20 and oleth-20. All IDE loaded SLN showed a mean particle size in the range of 30-49 nm and a single peak in size distribution. In vitro permeation/penetration experiments were performed on pig skin using Franz-type diffusion cells. IDE penetration into the different skin layers depended on the type of SLN used while no IDE permeation occurred from all the SLN under investigation. The highest IDE content was found in the epidermis when SLN contained ceteth-20 or isoceteth-20 as surfactant while IDE distribution into the upper skin layers depended on the amount of IDE loaded when oleth-20 was used as surfactant. These results suggest that the SLN tested could be an interesting carrier for IDE targeting to the upper skin layers.

Topics: Animals; Antioxidants; Cetomacrogol; Drug Delivery Systems; Ethers; Feasibility Studies; Lipids; Nanoparticles; Particle Size; Permeability; Plant Oils; Polyethylene Glycols; Skin Absorption; Surface-Active Agents; Swine; Tissue Distribution; Ubiquinone

Solid lipid nanoparticles (SLN) are regarded as interesting drug delivery systems and their preparation techniques have gained a great deal of attention.. To evaluate the feasibility of preparing idebenone (IDE) loaded SLN from O/W microemulsions by the phase-inversion temperature (PIT) method. Since SLN have been proposed to improve drug delivery to the brain, IDE was chosen as model drug due to its activity in the treatment of neurodegenerative diseases.. Cetyl palmitate was used as solid lipid to prepare SLN containing two surfactant/cosurfactant mixtures, isoceteth-20/glyceryl oleate (SLN A) and ceteth-20/glyceryl oleate (SLN B) by the PIT method.. All the formulations tested showed a mean particle diameter ranging from 30 to 95 nm and a single peak in size distribution. Stability tests showed that SLN B were more stable than SLN A. IDE release was dependent both on the type of primary surfactant used and the amount of loaded drug. IDE-loaded SLN were effective in inhibiting 2,2'-azobis-(2-amidinopropane)dihydrochloride (APPH)-induced lactic dehydrogenase (LDH) release and reactive oxygen species (ROS) production in primary cultures of astrocytes obtained from rat cerebral cortex. It is noteworthy that SLN B2 (containing ceteth-20 as primary surfactant and 0.7% w/w IDE) were able to prevent entirely both the LDH release and ROS production induced by APPH.. The PIT method provided SLN with good technological properties. The tested SLN could be regarded as interesting carriers to overcome the blood brain barrier and increase the efficacy of the loaded drug.

Topics: Animals; Antioxidants; Astrocytes; Blood-Brain Barrier; Cerebral Cortex; Cetomacrogol; Drug Delivery Systems; Drug Stability; Emulsions; Ethylene Glycols; Fatty Alcohols; Glycerides; In Vitro Techniques; Nanoparticles; Palmitates; Particle Size; Rats; Rats, Wistar; Reactive Oxygen Species; Surface-Active Agents; Tissue Distribution; Ubiquinone