ABSTRACT
Myriocin is an antibiotic derived from Mycelia sterilia, and is a potent inhibitor of serine palmitoyltransferase, the enzyme involved in the first step of sphingosine synthesis. Myriocin, inhibiting ceramide synthesis, has a great potential for treatment of diseases characterized by high ceramide levels in affected tissues, such as retinitis pigmentosa (RP). Drug delivery to the retina is a challenging task, which is generally by-passed through intravitreal injection, that represents a risky invasive procedure. We, therefore, developed and characterized an ophthalmic topical nanotechnological formulation based on a nanostructured lipid carrier (NLC) and containing myriocin. The ocular distribution of myriocin in the back of the eye was assessed both in rabbits and mice using LC-MS/MS. Moreover, rabbit retinal sphingolipid and ceramides levels, after myriocin-NLC (Myr-NLC) eye drops treatment, were assessed. The results demonstrated that Myr-NLC formulation is well tolerated and provided effective levels of myriocin in the back of the eye both in rabbits and mice. We found that Myr-NLC eye drops treatment was able to significantly decrease retinal sphingolipid levels. In conclusion, these data suggest that the Myr-NLC ophthalmic formulation is suitable for pharmaceutical development and warrants further clinical evaluation of this eye drops for the treatment of RP.
Subject(s)
Fatty Acids, Monounsaturated/pharmacology , Ophthalmic Solutions/pharmacology , Retina/drug effects , Retinitis Pigmentosa/drug therapy , Animals , Ceramides/metabolism , Chemistry, Pharmaceutical/methods , Drug Carriers/chemistry , Drug Delivery Systems/methods , Fatty Acids, Monounsaturated/chemistry , Lipids/chemistry , Mice , Nanostructures/chemistry , Ophthalmic Solutions/chemistry , Rabbits , Retina/metabolism , Retinitis Pigmentosa/metabolism , Serine C-Palmitoyltransferase/metabolism , Sphingolipids/metabolismABSTRACT
Trans-resveratrol (RSV) was microencapsulated in Eudragit® RS100 and RL100 resin blends. Lyophilized microspheres were characterized in the solid state for their micromeritic properties and drug loading. FT-IR, PXRD, and DSC analyzes suggested that RSV formed an intimate microcrystalline dispersion within the polymer network, also confirmed by SEM analysis. This produced a reduced degradation of RSV after storage at 40 °C, compared to the neat drug, and a protection of the drug from UV light-induced trans-cis isomerization (60% intact drug was found after 60 s irradiation at 350 nm, compared to 37% for the pure drug). Solubility and in vitro dissolution studies indicated that microencapsulation did not improve the dissolution pattern of RSV in simulated gastric and intestinal aqueous fluids. Evaluation of the in vitro antioxidant activity showed that, compared to the neat drug in aqueous solution, RSV loaded in the microspheres retained for a longer time, up to 22 days of incubation, the initial ORAC capacity. The present study thus demonstrated that Eudragit® Retard resins can be used to easily produce micro-sized solid dispersions with RSV, for potential oral administration, contributing to ameliorate the physico-chemical stability and antioxidant activity of this compound.
Subject(s)
Acrylates/chemistry , Antioxidants/chemistry , Polymers/chemistry , Resveratrol/chemistry , Acrylic Resins/chemistry , Calorimetry, Differential Scanning/methods , Drug Compounding/methods , Microspheres , Polymethacrylic Acids/chemistry , Solubility , Spectroscopy, Fourier Transform Infrared/methodsABSTRACT
Curcumin (diferuloymethane; CUR) is a yellow pigment used in traditional medicine throughout history for its anti-inflammatory activity. In the last years, the scientific research has demonstrated that CUR effects are related to the modulation of crucial molecular targets, related to several pathologies including cancer, arthritis, diabetes, Crohn's disease. In this paper, two formulations of microencapsulated CUR obtained by coevaporation with polymethacrylate polymers (Eudragit® Retard) were investigated in vitro, ex vivo, and in vivo, and results were compared by laser confocal microscopy analysis. The permeation of microencapsulated CUR through CaCo-2 monolayers was evaluated in vitro. The mucoadhesion and bioadhesion of the CUR-loaded microparticles were evaluated in vitro, using E12 and CaCo-2 human intestinal cells, and ex vivo, by means of excised rat intestinal mucosa. After oral administration to rats, microencapsulated CUR showed a sevenfold increase of bioavailability in respect to the neat drug, with a concomitant reduction of the Tmax and a five-fold plasma concentration peak increase.
