Double-Walled Poly-(D,L-lactide-co-glycolide) (PLGA) and Poly(L-lactide) (PLLA) Nanoparticles for the Sustained Release of Doxorubicin.

Double-walled nanoparticles (DWNPs), containing doxorubicin as a model drug, were produced using poly-(D,L-lactide-co-glycolide) (PLGA) and poly(L-lactide) (PLLA) by the solvent evaporation technique. Double-walled microparticles containing doxorubicin were also produced to make possible the examination of the inner morphology and drug distribution using optical and fluorescence microscopy. The produced microparticles present a double-walled structure with doxorubicin solubilized in the PLGA-rich phase. The DWNPs produced present very low initial burst values and a sustained DOX release for at least 90 days with release rates decreasing with the increase in the PLLA amount. Zero-order release kinetics were obtained after day 15. The results support that the PLLA layer acts as a rate control barrier and that the diffusion of doxorubicin from the drug-loaded inner PLGA core can be retarded by an increase in the thickness of the unloaded outer layer. The unloaded double-walled nanoparticles produced were used in in vitro tests with CHO cells and demonstrate that they are nontoxic, while the double-walled nanoparticles loaded with doxorubicin caused a great cellular viability and decreased when tested in vitro.

Signo y síndrome de Chilaiditi / Sign and Chilaiditi síndrome

El signo de Chilaiditi consiste en la interposición permanente o temporal del colon, el intestino delgado o el estómago en el espacio hepatodiafragmático. Este hallazgo es raro, con una incidencia radiológica del 0,025-0,028% de la población. Cuando está asociado a una sintomatología gastrointestinal, se designa como síndrome de Chilaiditi. Las dos entidades son benignas y no requieren tratamiento quirúrgico

Chilaiditi sign means that a permanent or temporary interposition of the colon, small intestine or stomach is visible on the X-ray at the level of hepatodiaphragmatic space. This finding is rare, with a radiological incidence of 0.025 to 0.028% of the population. The Chilaiditi syndrome occurs with the onset of digestive symptoms such as abdominal pain or acute bowel obstruction. These two findings are benign and do not require surgical treatment

Doxorubicin-loaded galactose-conjugated poly(d,l-lactide-co-glycolide) nanoparticles as hepatocyte-targeting drug carrier.

The objective of this work is to produce doxorubicin-loaded galactose-conjugated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) to be specifically recognised by human hepatoma cellular carcinoma (Hep G2) cells and assess NPs cytotoxicity. Doxorubicin-unloaded and doxorubicin-loaded galactose-conjugated PLGA NPs were prepared using an emulsion method and characterised for morphology, size, drug release behaviour, Hep G2 recognition and cell cytotoxicity. The produced doxorubicin-loaded PLGA-galactose-conjugate nanoparticles (PLGA-GAL NPs) are spherical in shape with a size of 365 ± 74 nm, a drug encapsulation efficiency of 69% and released in a biphasic pattern with higher release rates at pH 5. In vitro cell studies confirmed the specific interaction between the receptors of Hep G2 and the PLGA-GAL NPs. Cell cytotoxicity tests showed that unloaded NPs are non-toxic and that doxorubicin-loaded NPs caused a cellular viability decrease of around 80%, therefore representing a promising approach to improve liver-specific drug delivery.

Anti-CD8 conjugated nanoparticles to target mammalian cells expressing CD8.

This work aimed at the development of targeted drug delivery systems using nanoparticles fused with antibodies. The antibody anti-human CD8 was coupled onto PLGA nanoparticles, and the ability of these particles to specifically target cells expressing CD8 was studied. The obtained particles were found to be of spherical shape exhibiting a size between 350 and 600 nm. In vitro experiments with different cellular cultures (TE671, CHO and HEK293) using unmodified nanoparticles containing rhodamine have shown that particles were present on their surface within 48 h of incubation. In vitro tests using anti-CD8 conjugated nanoparticles in CHO cell cultures indicated that all transfected cells which express CD8 show these particles on their surface within 1h of incubation. These results demonstrated that, in a shorter time, the produced particles can target cells expressing CD8 on their surface which offers the ability to reduce drug side effects. The antibody-coupled nanoparticles represent a promising approach to improve the efficacy of active targeting for lymphoblastic leukaemia therapy.

Biocompatible and bioactive gum Arabic coated iron oxide magnetic nanoparticles.

The surface modification of iron oxide magnetic nanoparticles (MNPs) with gum Arabic (GA) via adsorption and covalent coupling was studied. The adsorption of GA was assessed during MNP chemical synthesis by the co-precipitation method (MNP_GA), and after MNP synthesis on both bare magnetite and MNP_GA. The covalent immobilization of GA at the surface of aldehyde-activated (MNP_GA(APTES)) or aminated MNPs (MNP_GA(EDC)) was achieved through free terminal amino and carboxylate groups from GA. The presence of GA at the surface of the MNPs was confirmed by FTIR and by the quantification of GA by the bicinchoninic acid test. Results indicated that the maximum of GA coating was obtained for the covalent coupling of GA through its free carboxylate groups (MNP_GA(EDC)), yielding a maximum of 1.8g of GA bound/g of dried particles. The hydrodynamic diameter of MNPs modified with GA after synthesis resulted in the lowest values, in opposition to the MNPs co-precipitated with GA which presented the tendency to form larger aggregates of up to 1mum. The zeta potentials indicate the existence of negatively charged surfaces before and after GA coating. The potential of the GA coated MNPs for further biomolecule attachment was assessed through anchorage of a model antibody to aldehyde-functionalized MNP_GA and its subsequent detection with an FITC labeled anti-antibody.

Chloride channels in the eel intestine

Patches of freshly isolated epithelial cells from eel Anguilla anguilla intestine bathed by the same solution on both sides in the cell-attached configuration had conductances of 57.0+/-1.8 pS (for positive voltages) and 13.3+/-0.7 pS (for negative voltages) (means +/- s.e.m., N=25). Electrical activity was spontaneous in the cell-attached configuration, but was frequently lost after excision. In inside-out patches, channel activity was restored by strong hyperpolarization (-150 mV for 5 s) or depolarization (+150 mV for 5 s). Channel activity was inhibited by the Cl- transport blocker DIDS (1 mmol l-1). The membrane potential measured using the nystatin slow whole-cell technique in primary cultured eel intestine epithelial cells was -35.4+/-1.0 mV (N=14), similar to the expected equilibrium potential for Cl- (-38.2 mV). Removal of Cl- from the bath or application of DIDS caused 16 mV and 6-7 mV depolarizing shifts in reversal potential, respectively. In one experiment, DIDS also induced a reduction in cell conductance from 0. 011+/-0.014 to 0.002+/-0.005 nS. The addition of 0.5 mmol l-1 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (a membrane-permeable analogue of cyclic AMP) to the bath caused an increase in conductance without affecting the reversal potential.