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This paper describes the evaluation of polymeric nanoparticles (NPs) as a potential carrier for lung administration of fluticasone propionate (FP). The chosen polymeric material to produce NPs was a copolymer based on α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) whose backbone was derivatised with different molecules, such as poly(lactic acid) (PLA) and polyethylenglycol (PEG). The chosen method to produce NPs from PHEA-PLA-PEG2000 was the method based on high-pressure homogenization and subsequent solvent evaporation by adding Pluronic F68 during the process and trehalose before lyophilisation. Obtained colloidal FP-loaded NPs showed a slightly negative surface charge and nanometric dimensions that are maintained after storage for one year at -20 °C and 5 °C. The FP loading was about 2.9 wt % and the drug was slowly released in simulated lung fluid. Moreover, the obtained NPs, containing the drug or not, were biocompatible and did not induce cell necrosis and cell apoptosis on bronchial epithelial cells (16-HBE). Further in vitro testing on cigarette smoke extract (CSE)-stimulated 16-HBE revealed that FP-loaded NPs were able to reduce the survivin expression, while either free FP or empty NPs were not able to significantly reduce this effect. [ABSTRACT FROM AUTHOR]

Background In hepatocellular carcinoma (HCC), different signaling pathways are de-regulated, and among them, the expression of the epidermal growth factor receptor (EGFR). Tyrphostin AG- 1478 is a lipophilic low molecular weight inhibitor of EGFR, preferentially acting on liver tumor cells. In order to overcome its poor drug solubility and thus improving its anticancer activity, it was entrapped into nanostructured lipid carriers (NLC) by using safe ingredients for parenteral delivery. Results Nanostructured lipid carriers (NLC) carrying tyrphostin AG-1478 were prepared by using the nanoprecipitation method and different matrix compositions. The best system in terms of mean size, PDI, zeta potential, drug loading and release profile was chosen to evaluate the anti-proliferative effect of drug-loaded NLC versus free drug on human hepatocellular carcinoma HA22T/VGH cells. Conclusions Thanks to the entrapment into NLC systems, tyrphostin AG-1478 shows an enhanced in vitro anti-tumor activity compared to free drug. These finding raises hope of future drug delivery strategy of tyrphostin AG-1478 -loaded NLC targeted to the liver for the HCC treatment. [ABSTRACT FROM AUTHOR]

ABSTRACT Pulsed electron-beam irradiation of a semi-dilute poly( N-vinyl pyrrolidone) (PVP) aqueous solution in the presence of acrylic acid has led to a carboxyl functionalized nanogel system. Nanoparticles hydrodynamic size and surface charge density, in water and as a function of pH, were investigated by dynamic light scattering and laser doppler velocimetry, respectively. Nanogels (NGs) were proved not to be cytotoxic at the cellular level. Indeed, they rapidly bypass the cellular membrane to accumulate in specific cell portions of the cytoplasm, in the perinuclear area. The availability of pendant carboxyl groups on the crosslinked PVP NGs core prompted us to attempt their decoration with a single strand oligonucleotide, which holds a terminal amino group. The recognition ability of the attached single helix of its complementary strand was investigated. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39774. [ABSTRACT FROM AUTHOR]

Amphiphilic cyclodextrin (ACyD) provideswater-soluble and adaptablenanovectors by modulating the balance between the hydrophobic andhydrophilic chains at both CyD sides. This work aimed to design nanoassembliesbased on nonionic and hydrophilic ACyD (SC6OH) for the delivery ofa poor-water-soluble organotin(IV)-porphyrin derivative [(Bu3Sn)4TPPS] to melanoma cancer cells. To characterize theporphyrin derivatives under simulated physiological conditions, aspeciation was performed using complementary techniques. In aqueoussolution (≤20 μM), (Bu3Sn)4TPPSprimarily exists as a monomer (2in Figure 1), as suggested by the low static anisotropy (ρ ≈0.02) with a negligible formation of porphyrin supramolecular aggregates.MALDI-TOF spectra indicate the presence of moieties (i.e., [(Bu3Sn)3TPPS]−) that are derivativesof the monomeric species. Spectrofluorimetry coupled with potentiometricmeasurements primarily assesses the presence of the hydrolytic [(Bu3Sn)4TPPS (OH)4]4–speciesunder physiological conditions. Nanoassemblies of (Bu3Sn)4TPPS/SC6OH were prepared by dispersion of organic films inPBS at pH 7.4 and were investigated using a combination of spectroscopicand morphological techniques. The UV–vis and emission fluorescencespectra of the (Bu3Sn)4TPPS/SC6OH reveal shiftsin the peculiar bands of the organotin(IV)-porphyrin derivative dueto its interaction with the ACyD supramolecular assemblies in aqueoussolution. The mean size was within the range of 100–120 nm.The ξ-potential was negative (−16 mV) for the (Bu3Sn)4TPPS/SC6OH nanoassemblies, with an entrapmentefficiency of approximately 67%. The intracellular delivery, cytotoxicity,nuclear morphology and cell growth kinetics were evaluated via fluorescencemicroscopy on A375 human melanoma cells. The delivery of (Bu3Sn)4TPPS by ACyD with respect to free (Bu3Sn)4TPPS increases the internalization efficiency and cytotoxicityto induce apoptotic cell death and, at lower concentrations, changesthe cellular morphology and prevents cell proliferation. [ABSTRACT FROM AUTHOR]

(1) Background: A new family of nanosystems able to discern between normal and tumor cells and to release a therapeutic agent in controlled way were synthetized by e-beam irradiation. This technique permits to obtain biocompatible, sterile, carboxyl-functionalized polyvinylpyrrolidone (PVP-co-acrylic acid) nanogels (NGs); (2) Methods: Here, we performed a targeting strategy based on the recognition of over-expressed proteins on tumor cells, like the folate receptor. The selective targeting was demonstrated by co-culture studies and flow cytometry analysis, using folate conjugated NGs. Moreover, nanoparticles were conjugated to a chemotherapeutic drug or to a pro-apoptotic siRNA through a glutathione sensitive spacer, in order to obtain a controlled release mechanism, specific for cancer cells. The drug efficiency was tested on tumor and healthy cells by flow cytometric analysis, confocal and epifluorescence microscopy and cytotoxicity assay; the siRNA effect was investigated by RNAi experiment; (3) Results: The data obtained showed that the use of NGs permits a faster cargo release in cancer cells, in response to high cytosolic glutathione level, also improving their efficacy; (4) Conclusion: The possibility of releasing biological molecules in a controlled way and to recognize a specific tumor target allows overcoming the typical limits of the classic cancer therapy.

Chronic liver diseases represent a major global health problem both for their high prevalence worldwide and, in the more advanced stages, for the limited available curative treatment options. In fact, when lesions of different etiologies chronically affect the liver, triggering the fibrogenesis mechanisms, damage has already occurred and the progression of fibrosis will have a major clinical impact entailing severe complications, expensive treatments and death in end-stage liver disease. Despite significant advances in the understanding of the mechanisms of liver fibrinogenesis, the drugs used in liver fibrosis treatment still have a limited therapeutic effect. Many drugs showing potent antifibrotic activities in vitro often exhibit only minor effects in vivo because insufficient concentrations accumulate around the target cell and adverse effects result as other non-target cells are affected. Hepatic stellate cells play a critical role in liver fibrogenesis , thus they are the target cells of antifibrotic therapy. The application of nanoparticles has emerged as a rapidly evolving area for the safe delivery of various therapeutic agents (including drugs and nucleic acid) in the treatment of various pathologies, including liver disease. In this review, we give an overview of the various nanotechnology approaches used in the treatment of liver fibrosis.

In this chapter, the main production methods of lipid nanostructures such as solid lipid nanoparticles and nanostructured lipid carriers, and their application are described. In particular, we describe the strategies commonly used to obtain lipid nanoparticles to overcome the blood-brain barrier (BBB) for the treatment of several brain diseases. The use of these carriers as targeted drug delivery systems is associated with many advantages that include excellent storage stability, easy production without the use of any organic solvent, the possibility of steam sterilization and lyophilization, and large scale production. They exhibit good stability during long-term storage, consist of physiologically well-tolerated ingredients often already approved for pharmaceutical applications in humans, and are generally recognized as safe. Under optimized conditions, they can be produced to incorporate several drugs and therapeutic proteins. Formulation in solid lipid nanostructures confers improved drug loading and protein stability, targeting, and sustained release of the incorporated molecules. Moreover, their lipophilic features lead them to the central nervous system by an endocytotic mechanism, overcoming the BBB. Many drugs have been incorporated into solid lipid nanosystems and several therapeutic applications may be foreseen, such as targeting with molecules useful for treatment of brain diseases., (Copyright © 2012 Elsevier Inc. All rights reserved.)

From the aerial parts of Teucrium montbretii subsp. libanoticum 10 neoclerodane diterpenoids were isolated. Three of them are new [3beta-hydroxyteubutilin A (1), 12-epi-montanin G (2), 20-epi-3,20-di-O-deacetylteupyreinidin (3)], whereas the other seven, namely, 6-ketoteuscordin (4), teuscordinon (5), 6beta-hydroxyteuscordin (6), montanin D (7), 3,20-di-O-deacetylteupyreinidin (8), montanin G (9), and 3-O-deacetylteugracilin A (10), are previously known structures. The structures of 1-3 were determined by spectral and chemical methods.