Improving dexamethasone drug loading and efficacy in treating arthritis through a lipophilic prodrug entrapped into PLGA-PEG nanoparticles.

Targeted delivery of dexamethasone to inflamed tissues using nanoparticles is much-needed to improve its efficacy while reducing side effects. To drastically improve dexamethasone loading and prevent burst release once injected intravenously, a lipophilic prodrug dexamethasone palmitate (DXP) was encapsulated into poly(DL-lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs). DXP-loaded PLGA-PEG NPs (DXP-NPs) of about 150 nm with a drug loading as high as 7.5% exhibited low hemolytic profile and cytotoxicity. DXP-NPs were able to inhibit the LPS-induced release of inflammatory cytokines in macrophages. After an intravenous injection to mice, dexamethasone (DXM) pharmacokinetic profile was also significantly improved. The concentration of DXM in the plasma of healthy mice remained high up to 18 h, much longer than the commercial soluble drug dexamethasone phosphate (DSP). Biodistribution studies showed lower DXM concentrations in the liver, kidneys, and lungs when DXP-NPs were administered as compared with the soluble drug. Histology analysis revealed an improvement in the knee structure and reduction of cell infiltration in animals treated with the encapsulated DXP compared with the soluble DSP or non-treated animals. In summary, the encapsulation of a lipidic prodrug of dexamethasone into PLGA-PEG NPs appears as a promising strategy to improve the pharmacological profile and reduce joint inflammation in a murine model of rheumatoid arthritis.

Development of the eye in the turbot Psetta maxima (Teleosti) from hatching through metamorphosis.

Development of the eyes during the larval and metamorphic stages of the turbot Psetta maxima (Teleosti) was studied using microscopy. Events during differentiation of both eyes occur simultaneously, and no differences between he migrating and no-migrating eye were observed during metamorphosis. At hatching, the eyes are rudimentary, consisting of a neuroepithelial optic cup and a small lens. During larval development, major changes occur in the lens and retina, in which cones are the only photoreceptors. The appearance of rods is delayed until metamorphosis. The outer ocular layers (sclera and choroid) arise during larval development as thin connective layers with little differentiation. These layers undergo important changes just before and during metamorphosis. These results indicate that development of the individual components of the eye occurs at different times. Those of ectodermal origin appear early, providing a simple visual organ during larval life. By metamorphosis, the eye shows adult characteristics, including two types of photoreceptors, a rich choroid vascular supply and ocular structures involved in protecting, shaping, and moving the eye. J Morphol 233:31-42, 1997. © 1997 Wiley-Liss, Inc.