There is a growing body of evidence to suggest that cannabinoids are beneficial for a range of clinical conditions, including pain, inflammation, epilepsy, sleep disorders, the symptoms of multiple sclerosis, anorexia, schizophrenia and other conditions. The transformation of cannabinoids from herbal preparations into highly regulated prescription drugs is therefore progressing rapidly. The development of such drugs requires well-controlled clinical trials to be carried out in order to objectively establish therapeutic efficacy, dose ranges and safety. The low oral bioavailability of cannabinoids has led to feasible methods of administration, such as the transdermal route, intranasal administration and transmucosal adsorption, being proposed. The highly lipophilic nature of cannabinoids means that they are seen as suitable candidates for advanced nanosized drug delivery systems, which can be applied via a range of routes. Nanotechnology-based drug delivery strategies have flourished in several therapeutic fields in recent years and numerous drugs have reached the market. This review explores the most recent developments, from preclinical to advanced clinical trials, in the cannabinoid delivery field, and focuses particularly on pain and inflammation treatment. Likely future directions are also considered and reported.

The flavonoid quercetin is extensively studied for its antioxidant and chemopreventive properties.However the poor water-solubility, low stability and short half-life could restrict its use in skin care products and therapy.The present study is aimed to evaluate the potential of aminopropyl functionalized mesoporous silica nanoparticles (NH 2 -MSN) as topical carrier system for quercetin delivery. Thermo gravimetric analysis, X-ray diffraction, high resolution transmission electron microscopy, nitrogen adsorption isotherms, FT-IR spectroscopy, zeta potential measurements and differential scanning calorimetry allowed analyzing with great detail the organic-inorganic molecular interaction.The protective effect of this vehicle on UV-induced degradation of the flavonoid was investigated revealing a certain positive influence of the inclusion on the photostability over time.Epidermal accumulation and transdermal permeation of this molecule were ex vivo evaluated using porcine skin mounted on Franz diffusion cells. The inclusion complexation with the inorganic nanoparticles increased the penetration of quercetin into the skin after 24 h post-application without transdermal delivery.The effect of quercetin alone or given as complex with NH 2 -MSN on proliferation of JR8 human melanoma cells was evaluated by sulforhodamine B colorimetric proliferation assay. At a concentration 60 M the complex with NH 2 -MSN was more effective than quercetin alone, causing about 50% inhibition of cell proliferation.

Oxidosqualene cyclase of the yeast encoded by the ERG7 gene converts oxidosqualene to lanosterol, the first cyclic component of sterol biosynthesis. In a previous study (Athenstaedt, K., Zweytick, D., Jandrositz, A, Kohlwein, S. D., and Daum, G. (1999) J. Bacteriol. 181, 6441-6448), Erg7p was identified as a component of yeast lipid particles. Here, we present evidence that Erg7p is almost exclusively associated with this compartment as shown by analysis of enzymatic activity, Western blot analysis, and in vivo localization of Erg7p-GFP. Occurrence of oxidosqualene cyclase in other organelles including the endoplasmic reticulum is negligible. In an erg7 deletion strain or in wild-type cells treated with an inhibitor of oxidosqualene cyclase, the substrate of Erg7p, oxidosqualene, accumulated mostly in lipid particles. Storage in lipid particles of this intermediate produced in excess may provide a possibility to exclude this membrane-perturbing component from other organelles. Thus, our data provide evidence that lipid particles are not only a depot for neutral lipids, but also participate in coordinate sterol metabolism and trafficking and serve as a storage site for compounds that may negatively affect membrane integrity. Oxidosqualene cyclases (OSCs)1 play a central role in sterol biosynthesis because they catalyze a key reaction of the sterol biosynthetic pathway, namely formation of a cyclic component from the acyclic precursors oxidosqualene and dioxidosqualene ( Fig. 1). OSCs may be regarded as phylogenetic markers insofar as they form a variety of cyclic triterpenoids in plants, whereas their only cyclization product in nonphotosynthetic eukaryotes such as animals, yeast, and other fungi is lanosterol (1). During the last 20 years studies on OSCs focused on several biochemical, molecular biological, and cell biological aspects.Hundreds of inhibitors were synthesized and tested for their effect on this enzyme (2-6), OSCs from different sources were characterized and purified (7-10), and genes encoding these proteins in various species were cloned and sequenced (11)(12)(13)(14)(15). During these studies, however, the important question as to the subcellular localization of this enzyme was surprisingly ignored. This aspect is essential because localization of enzymes involved in the sterol biosynthetic pathway may contribute greatly to the understanding of coordination and regulation of this pathway and of sterol traffic among organelles (16 -19).Subcellular localization of yeast OSC, which is encoded by the ERG7 gene, stimulated our interest not only because Erg7p is one of the most important enzymes of sterol biosynthesis that has not been localized so far, but also because targeting of the protein to its proper cellular environment may help to explain its mode of action and to design new inhibitors of OSC. As an example, we reported recently that some OSC inhibitors that undergo metabolic transformations in the yeast exhibit different effects because of different subcellular distribution of target protei...

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