Structuring and de-structuring of nanovectors from algal lipids. Part 1: physico-chemical characterization.

Lipid nanocarriers are among the most employed systems for drug delivery purposes in several research and industrial sectors, since their favorable properties ensure broad applicability. The design and characterization of these nanosystems are of paramount importance to obtain controlled outcome, since the supramolecular structure and molecular interactions deeply impact the functionality of the resulting aggregates. The choice of the most appropriate formulation for the target of interest relies on in-depth physico-chemical characterization in order to optimize stability, loading rates and sustained release. Several supramolecular architectures suited for carrier development can be obtained from lipid building blocks, by varying lipid composition and packing parameter. In particular, cubosome and liposome aggregates are often used as drug vectors thanks to their high cargo capability and biocompatibility. Moreover, the possibility to employ lipids from natural sources i.e. biomasses to prepare nanosystems makes them especially attractive. In this work, two aggregate types were characterized and compared as drug vectors for poorly water-soluble antioxidants, particularly curcumin and two adjuvants (i.e. tocopherol and piperine). The nanovectors were obtained by extracting lipids from algal biomasses with different lipid composition, and characterized by advanced structural (DLS, SAXS, Cryo-TEM) techniques, spectroscopy (NMR) and calorimetry (ITC). Finally, the structural stability of both aggregate types was evaluated.

Carborane derivatives loaded into liposomes as efficient delivery systems for boron neutron capture therapy.

Boron neutron capture therapy (BNCT) is an anticancer therapy based on the incorporation of (10)B in tumors, followed by neutron irradiation. Recently, the synthesis and delivery of new boronated compounds have been recognized as some of the main challenges in BNCT application. Here, we report on the use of liposomes as carriers for BNCT active compounds. Two carborane derivatives, i.e., o-closocarboranyl beta-lactoside (LCOB) and 1-methyl-o-closocarboranyl-2-hexylthioporphyrazine (H(2)PzCOB), were loaded into liposomes bearing different surface charges. The efficacy of these formulations was tested on model cell cultures, that is, DHD/K12/TRb rat colon carcinoma and B16-F10 murine melanoma. These induce liver and lung metastases, respectively, and are used to study the uptake of standard BNCT drugs, including borophenylalanine (BPA). Boron concentration in treated cells was measured by alpha spectrometry at the TRIGA mark II reactor (University of Pavia). Results showed high performance of the proposed formulations. In particular, the use of cationic liposomes increased the cellular concentration of (10)B by at least 30 times more than that achieved by BPA.

Cu(II) complexes in bacterial growth medium: electron spin resonance study.

In this study we report a spectroscopic investigation on the structure and stability of Cu(II)-complexes that are formed in a minimum growth medium (MM), normally used for Bacillus subtilis cultures. As other transition metals, Cu(II) compounds are toxic to this bacterium and the toxicity depends on the Cu(II) concentration. MM contained NH4+ ions and asparagine (asn) as the source of inorganic and organic nitrogen. Both ESR and electronic spectra demonstrated the very important role played by the amino acid asparagine in the coordinative behaviour of Cu(II). In particular, three different complexes were evidenced: Cu(H2O)6(2+); Cu(asn)+ and Cu(asn)2. The relative amount of these three species strongly depended on pH, on Cu:asn ratio and on the presence of the phosphate ions. They were identified and evaluated quantitatively by extensive simulation of the electron spin resonance (ESR) spectra recorded in different experimental conditions. The bis-complex was found to be more stable in MM than in an asparagine-containing water solution with the same Cu:asn ratio. A comparison of the spectroscopic results with microbiological investigations is also made.

Stability of water-soluble and lipid-soluble paramagnetic probes in Bacillus subtilis.

Batch cultures of the Gram-positive bacterium Bacillus subtilis PB19 have been investigated for their metabolic action to electron spin resonance (ESR) probes. Five- and six-membered water-soluble and lipid-soluble nitroxides have been used, which were reduced most probably to the corresponding hydroxylamine derivatives. The reduction was followed by the ESR signal intensity and found to be dependent on chemical structure and stability, lipophilic/hydrophilic character, charge, concentration, and temperature. Water-soluble nitroxides did not show apparent toxicity towards B. subtilis, in contrast with n-DXSA (n=5, 12, 16) which were found to be strongly cytotoxic. The cytotoxicity depended on the position of the doxyl unit along the hydrocarbon chain. The hydrophilic nitroxides were reduced at a much slower rate relative to the lipophilic ones. Membrane diffusion was suggested to be a slower process relative to chemical reduction for water-soluble nitroxides. The lipophilic nitroxides were solubilized into the membrane where they were rapidly reduced with a reduction maximum at 303-310 K, which is the optimal growth temperature of B. subtilis, while an inactivation at higher temperatures was observed. Both toxicity and reduction rates of nitroxides strongly indicated that the reduction was an enzyme-mediated process taking place near the outer surface of the periplasmic membrane.

[Semiology of spinal meningiomas and neurinomas (author's transl)]. / Approche sémiologique des méningiomes et neurinomes rachidiens.

The last 60 patient who underwent surgery for neurinoma or meningioma of the spine provide the basis for this report. One-fourth of all cases of spinal cord compression are due to meningioma or neurinoma. Attention is drawn to the characteristic clinical features of these tumors, particularly their time-course, since diagnosis if often delayed. The sooner diagnosis is established, the better postoperative recovery will be, especially in elderly patients (60% of cases). Results of operative treatment are presented.