Nanostructured Lipid Carriers (NLC) as Vehicles for Topical Administration of Sesamol: In Vitro Percutaneous Absorption Study and Evaluation of Antioxidant Activity

Sesamol is a natural phenolic compound extracted from Sesamum indicum seed oil. Sesamol is endowed with several beneficial effects, but its use as a topical agent is strongly compromised by unfavorable chemical-physical properties. Therefore, to improve its characteristics, the aim of the present work was the formulation of nanostructured lipid carriers as drug delivery systems for topical administration of sesamol. Two different nanostructured lipid carrier systems have been produced based on the same solid lipid (Compritol® 888 ATO) but in a mixture with two different kinds of oil phase such as Miglyol® 812 (nanostructured lipid carrier-M) and sesame oil (nanostructured lipid carrier-PLUS). Morphology and dimensional distribution of nanostructured lipid carriers have been characterized by differential scanning calorimetry and photon correlation spectroscopy, respectively. The release pattern of sesamol from nanostructured lipid carriers was evaluated in vitro determining drug percutaneous absorption through excised human skin. Furthermore, an oxygen radical absorbance capacity assay was used to determine their antioxidant activity. From the results obtained, the method used to formulate nanostructured lipid carriers led to a homogeneous dispersion of particles in a nanometric range. Sesamol has been encapsulated efficiently in both nanostructured lipid carriers, with higher encapsulation efficiency values (> 90?%) when sesame oil was used as the oil phase (nanostructured lipid carrier-PLUS). In vitro evidences show that nanostructured lipid carrier dispersions were able to control the rate of sesamol diffusion through the skin, with respect to the reference formulations. Furthermore, the oxygen radical absorbance capacity assay pointed out an interesting and prolonged antioxidant activity of sesamol, especially when vehiculated by nanostructured lipid carrier-PLUS

Gastro-resistant spray-dryed Citrus aurantium extract microsystems: improvement of dissolution rate and pharmacological activity.

Purpose: a) to improve dissolution rate, bioavailability and shelf-life, of Citrus Aurantium extracts from peel, pulp and seeds rich in fiber and other substances with remarkable biological compounds such as flavonoids; and b) to investigate their pharmacological properties. Methods: Gastroresistant (G-R) microsystems were obtained by spraying CAP, Sodium alginate or Eudragit feed solutions in presence of enhancers of dissolution rate. The chemical-physical properties of the raw extract and G-R formulations were evaluated by solubility studies (USP 33), UV, HPLC, DSC, FTIR, X-ray, SEM and FM analyses. The stability test was performed according ICH guidelines. Evaluation of body weight, blood glucose and cholesterol levels were performed on male CD1 mice. Effects on hepatic steatosis and changes in the expression of fats transporter CD36 in the gut were also evaluated in mice fed with a fat diet. Results: The presence of the enhancers produced well-formed microparticles containing drug well coated by the polymers. All the enhancers were able to increase the dissolution rate of extract in the simulated intestinal medium without altering protective polymers ability in the acidic fluid. The spray-drying technique and process conditions selected were effective in microencapsulating and stabilizing the flavonoids content giving satisfactory encapsulation efficiency, product yield, morphology and enteric release.. Conclusion: This approach might be suitable for delivering natural bioactive extract such as Citrus Aurantium, avoiding gastric degradation of the molecule and improving its bioavailability from solid oral dosage forms

Heteroarylimino-4-thiazolidinones as inhibitors of cartilage degradation

2-Benzo[d]thiazolyl- and 2-benzo[d]isothiazolyl-imino-5-benzylidene-4-thiazolidinone derivatives were investigated as potential metalloproteinases (MMPs) inhibitors and evaluated for their antidegenerative activity on human chondrocyte cultures stimulated by IL-1 beta, using an experimental model that reproduces the mechanisms involved in osteoarthritic (OA) diseases. Cell viability, the amount of glycosaminoglycans (GAGs) and the production of nitric oxide (NO) were measured. The most potent compound, 5-(4-methoxy-benzylidene)-2-(benzo[d]isothiazol-3-ylimino)-thiazolidin-4-one (4b), a MMP-13 inhibitor at nanomolar concentration (IC50 = 0.036 mu M), could be considered as a lead compound for the development of novel clinical agents, inhibitors of cartilage degradation, for the treatment of OA

Nanostructured lipid dispersions for topical administration of crocin, a potent antioxidant from saffron (Crocus sativus L.)

Crocin, a potent antioxidant obtained fromsaffron, shows anticancer activity in in vivo models. Unfortunately unfavorable physicochemical features compromise its use in topical therapy. The present study describes the preparation and characterization of nanostructured lipid dispersions as drug delivery systems for topical administration of crocin and the evaluation of antioxidant and anti proliferative effects of crocin once encapsulated into nanostructured lipid dispersions. Nanostructured lipid dispersions based onmonoolein in mixturewith sodiumcholate and sodiumcaseinate have been characterized by cryo-TEM and PCS. Crocin permeation was evaluated in vitro by Franz cells, while the oxygen radical absorbance capacity assay was used to evaluate the antioxidant activity. Furthermore, the anti proliferative activity was tested in vitro by the MTT test using a human melanoma cell line. The emulsification of monoolein with sodium cholate and sodium caseinate led to dispersions of cubosomes, hexasomes, sponge systems and vesicles, depending on the employed emulsifiers. Permeation and shelf life studies demonstrated that nanostructured lipid dispersions enabled to control both rate of crocin diffusion through the skin and crocin degradation. The oxygen radical absorbance capacity assay pointed out an interesting and prolonged antioxidant activity of crocinwhile the MTT test showed an increase of crocin cytotoxic effect after incorporation in nanostructured lipid dispersions. Thiswork has highlighted that nanostructured lipid dispersions can protect the labilemolecule crocin from degradation, control its skin diffusion and prolong antioxidant activity, therefore suggesting the suitability of nano structured lipid dispersions for crocin topical administration