Determination of the cholecalciferol-lipid complex using a combination of comparative modelling and NMR spectroscopy

Exploration of the systemic disposition of macromols. in relation to their physicochem. properties, could be a strategy for designing targeting systems. This work deals with the investigation of the Vitamin D3 conformation in the phospholipid bilayer in order to define a possible preferred binding site at the C=O- or PO2-phospholipid moiety (structure-function studies) to be exploited into drug discovery efforts

From nanoemulsions to nanostructured lipid carriers: A relevant development in dermal delivery of drugs and cosmetics

Recent advances in nanotechnology have led to the development of nano-scale drugs and delivery systems to improve drug therapeutic effectiveness. Between the end of ′50 and the beginning of ′60, the first colloidal systems in the nano-metric range were achieved by chance. Several research highlighted the usefulness of these nano-carriers as drug delivery systems to overcome biological barriers later on. Since few drugs are effective after their topical application, due to the barrier function of the skin, colloidal systems have being widely explored as carriers to improve drug skin permeation. In particular, a great deal of attention has been paid to delivery systems based on highly biocompatible and biodegradable components such as lipids and phospholipids. As a result, different types of nano-carriers such as liposomes, microemulsions, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been developed. This review will focus on the nano-carriers arising from the first colloidal systems consisting of water, lipids and surfactants, i.e. microemulsions and their consequent improvement through the development of SLN and NLC. The properties of these nano-carriers will be discussed along with their applications as skin delivery systems both in pharmaceutical and cosmetic field

DIFFERENTIAL SCANNING CALORIMETRY STUDY ON DRUG RELEASE FROM AN INULIN-BASED HYDROGEL AND ITS INTERACTION WITH A BIOMEMBRANE MODEL:pH AND LOADING EFFECT

Inulin has been derivatized with methacrylic anhydride (MA) and succinic anhydride (SA) to obtain a methacrylated/succinilated derivative (INU-MA-SA) able to produce a pH sensitive hydrogel after UV irradiation. The hydrogel was characterized and loaded with diflunisal (10.4, 17 and 24%, w/w) chosen as a model drug. The drug release from INU-MA-SA-based hydrogel to a biomembrane model made by unilamellar vesicles of dimyristoylphosphatidyl-choline (DMPC) was investigated at pH 4.0 and 7.4 by differential scanning calorimetry (DSC) that appears to be a suitable technique to follow the transfer kinetics of a drug from a controlled release system to a biomembrane model. The drug release from the hydrogel was compared with the dissolution of drug solid form by examining the effects exerted on the thermotropic behaviour of the DMPC unilamellar vesicles. The transferred drug and the release rate were affected by the drug loading as well as by the pH of the external medium. In particular the release was not linearly related to the drug loading but an intermediate loading allowed a better release at both investigated pHs, with a faster and more complete release observed at pH 7.4

Mechanism of antibacterial action of three monoterpenes

In the present paper, we report the antimicrobial efficacy of three monoterpenes [linalyl acetate, ()menthol, and thymol] against the gram-positive bacterium Staphylococcus aureus and the gram-negative bacterium Escherichia coli. For a better understanding of their mechanisms of action, the capability of these three monoterpenes to damage biomembranes was evaluated by monitoring the release, following exposure to the compounds under study, of the water-soluble fluorescent marker carboxyfluorescein from unilamellar vesicles with different lipidic compositions (phosphatidylcholine, phosphatidylcholine/phosphatidylserine [9:1], phosphatidylcholine/ stearylamine [9:1], and phosphatidylglycerol/cardiolipin [9:1]). Furthermore, the interaction of the terpenes tested with dimyristoylphosphatidylcholine multilamellar vesicles as model membranes was monitored by means of differential scanning calorimetry. Finally, the results were related to the relative lipophilicity and water solubility of the compounds examined. Taken together, our findings lead us to speculate that the antimicrobial effect of ()menthol, thymol, and linalyl acetate may result, at least partially, from a perturbation of the lipid fraction of microorganism plasma membrane, resulting in alterations of membrane permeability and in leakage of intracellular materials. Besides being related to physicochemical characteristics of the drugs (such as lipophilicity and water solubility), this effect seems to be dependent on lipid composition and net surface charge of microbial membranes. Furthermore, the drugs might cross the cell membranes, penetrating into the interior of the cell and interacting with intracellular sites critical for antibacterial activity

The Effect of Poly(d,l-Lactide-co-Glycolide)-Alendronate Conjugate Nanoparticles on Human Osteoclast Precursors.

Nanoparticles (NPs) formed from polymers conjugated with bisphosphonates (BPs) allow the bone targeting of loaded drugs, such as doxorubicin, for the treatment of skeletal tumours. The additional antiosteoclastic effect of the conjugated BP could contribute to the inhibition of tumour-associated bone degradation. With this aim, we have produced NPs made of poly(d,l-lactide-co-glycolide) (PLGA) conjugated with alendronate (ALE). To show if ALE retained the antiosteoclastic properties after the conjugation with PLGA and the production of NPs, we treated human osteoclasts, derived from circulating precursors, with PLGA-ALE NPs and compared the effects on actin ring generation, apoptosis and type-I collagen degradation with those of free ALE and with NPs made of pure PLGA. PLGA-ALE NPs disrupted actin ring, induced apoptosis and inhibited collagen degradation. Unexpectedly, also NPs made of pure PLGA showed similar effects. Therefore, we cannot exclude that in addition to the observed antiosteoclastic activity dependent on ALE in PLGA-ALE NPs, there was also an effect due to pure PLGA. Still, as PLGA-ALE NPs are intended for the loading with drugs for the treatment of osteolytic bone metastases, the additional antiosteoclastic effect of PLGA-ALE NPs, and even of PLGA, may contribute to the inhibition of the disease-associated bone degradation