Polymeric nanoparticles as drug controlled release systems: a new formulation strategy for drugs with small or large molecular weight

We report a study evaluating the encapsulation and release modalities from poly(D,L lactic acid) (PLA) or poly(D,L-lactide-co-glicolide) (PLGA) micro- and nano-particles of the antiischemic drug N6-cyclopentyladenosine (CPA) and bovine serum albumin (BSA), chosen as protein model. The results obtained by classical preparation methods (nanoprecipitation, single or double emulsion/solvent evaporation) of the particles were compared with those obtained by their formulation with a novel method, employing a thermosensible gel of Pluronic F-127, whose aqueous solutions can be liquid when refrigerated, but gel upon warming. Our results indicate that CPA-loaded nanoparticles, obtained by classical methods, drastically reduce their drug content showing, moreover, any control of the drug release with respect to CPA-loaded microparticles. The novel preparation method allowed us to obtain, instead, CPA encapsulation values in nanoparticles similar to those obtained for microparticles, achieving also a weak control of the drug release. Any drastic reduction of BSA particle content was obtained by decreasing their size from micro- to nano-scales, independently on the employment of classical or novel preparation methods. Moreover, the size reduction induced only a weak increase of the BSA release rate. The patterns of protein released from micro- and nano-particles obtained by the same formulation method were similar. In particular, the micro- and nano-spheres prepared by double emulsion technique showed an incomplete BSA release, characterized by an elevated burst effect followed by a very slow phase. On the other hand, the release from micro- and nano-particles obtained by the novel method was complete and quite regular, being characterized by a little burst release followed by a fast phase. These results have been related to the strong BSA distribution (observed by confocal laser scanning microscope) in the surface or in the core of microparticles obtained by the classical or novel methods, respectively.     

How To Find a Needle (or Anything Else) in a Haystack: Two-Dimensional Correlation Spectroscopy-Filtering with Iterative Random Sampling Applied to Pharmaceutical Heparin

Risks of contamination of the major clinical anticoagulant heparin can arise from deliberate adulteration with unnatural or natural polysaccharides, including heparin from other animal sources, other natural products, or artifacts of manufacture, and these can escape detection by conventional means. Currently, there is no generally applicable, objective test recommended by regulators that can detect these in pharmaceutical heparin, and this continues to leave heparin exposed to contamination risks. Two-dimensional correlation spectroscopic-filtering with iterative random sampling (2D-COS-firs) is reported. It employs a difference covariance matrix with iterative random sampling, and is capable of revealing contamination in pharmaceutical heparin to a high level of sensitivity irrespective of the nature of those features. The technique is suitable to any situation in which a comparison of a single entity to a family of heterogeneous entities, particularly natural products and biosimilars, needs to be made, and will find application in pharmaceutical monitoring, manufacturing quality control, materials science, biotechnology, and metabolomic investigations.     

Filtration performance at high temperatures and analysis of ceramic filter elements during biomass gasification

During the CHRISGAS project, various experimental campaigns were performed with the aim to study the hot gas filtration process during steam-O₂ biomass gasification at Delft University of Technology. The test-rig consists of a 100 kW thermal atmospheric circulating fluidized-bed gasifier and a high temperature filter unit which contains 3 rigid ceramic candles with an outer diameter of 60 mm, 10 mm wall thickness and a length of 1520 mm. This paper gives an overview of tests performed with different fuels (A-wood, B-wood, miscanthus) and with sand and magnesite used as bed materials. Dia-Schumalith¹ candles were operated in the temperature range between 600 °C and 800 °C for more than 50 h. The filtration performance was studied through continuous observation of the increasing differential pressure while the filter cake formed on the surface of the candles. Gas face velocities ranged between 3 cm s^?1 and 5 cm s^?1. Stable filtration was achieved during some tests. Dust cake analysis indicated formation of calcium phosphates and silicates and potassium silicates.     

Experimental Damage Criterion for Static and Fatigue Life Assessment of Commercial Aluminum Alloy Die Castings

Metallurgical and Materials Transactions A - Defects, particularly porosity and oxides, in high-pressure die casting can seriously compromise the in-service behavior and durability of products...     

In vitro antimicrobial properties of silver–polysaccharide coatings on porous fiber-reinforced composites for bone implants

Biostable fiber-reinforced composite (FRC) implants prepared from bisphenol-A-dimethacrylate and triethyleneglycoldimethacrylate resin reinforced with E-glass fibers have been successfully used in cranial reconstructions in 15 patients. Recently, porous FRC structures were suggested as potential implant materials. Compared with smooth surface, porous surface allows implant incorporation via bone ingrowth, but is also a subject to bacterial attachment. Non-cytotoxic silver–polysaccharide nanocomposite coatings may provide a way to decrease the risk of bacterial contamination of porous FRC structures. This study is focused on the in vitro characterization of the effect porosity on the antimicrobial efficiency of the coatings against Staphylococcus aureus and Pseudomonas aeruginosa by a series of microbiological tests (initial adhesion, antimicrobial efficacy, and biofilm formation). Characterization included confocal laser scanning microscopy and scanning electron microscopy. The effect of porosity on the initial attachment of S. aureus was pronounced, but in the case of P. aeruginosa the effect was negligible. There were no significant effects of the coatings on the initial bacterial attachment. In the antimicrobial efficacy test, the coatings were potent against both strains regardless of the sample morphology. In the biofilm tests, there were no clear effects either of morphology or of the coating. Further coating development is foreseen to achieve a longer-term antimicrobial effect to inhibiting bacterial implant colonization.     

Fatty acid composition and CLA content in goat milk and cheese samples from Umbrian market

Goat dairy products are considered as a suitable alternative to cow milk products for some special categories of consumers (infants, old, and convalescent people). In the present research, a study on the lipid fraction of commercial goat milk and cheese samples purchased from Umbrian market was carried out. Particular attention has been paid to evaluating conjugated linoleic acid (CLA) content and determining some interesting nutritional indexes. The results of goat milk samples showed that saturated, monounsaturated and polyunsaturated fatty acid contents were on average 71.2, 23.4, and 3.8 %, respectively. CLA content (cis-9, trans-11 isomer) was on average 11.5 mg/100 g in milk. Considerable variability was observed for n6/n3 ratio that varied from 2.7 to 10.6 in the considered goat milk samples. With regard to goat cheese samples CLA concentration was on average 118.8 mg/100 g in fresh cheese and 217.7 mg/100 g in semi-hard cheese, and the difference was not significant. Interestingly, α-linolenic acid content was higher and n6/n3 ratio was lower in semi-hard with respect to fresh cheese samples (p < 0.05).     

Deactivation of riboflavin triplet-excited state by phenolic antioxidants: mechanism behind protective effects in photooxidation of milk-based beverages

The water-soluble plant polyphenols rutin, (+)-catechin, and (–)-epigallocatechin gallate were each found to be efficient quenchers for the triplet-excited state of riboflavin in aqueous solution using nano-second laser flash photolysis. The deactivation followed second-order kinetics with rates close to the diffusion control: (–)-epigallocatechin gallate (1.70±0.2×10⁹ l mol^–1 s^–1), (+)-catechin (1.44±0.04×10⁹ l mol^–1 s^–1), and rutin (9.7±0.2×10⁸ l mol^–1 s^–1) at 25 °C and pH = 6.8. No synergetic effects for mixtures of the phenolic compounds were found. Hydrogen atom transfer is calculated to be more exergonic than electron transfer, suggesting the hydrogen atom transfer mechanism to be operative. The efficient deactivation by the plant polyphenols makes this type of compounds of importance as protectors against light-induced oxidation in flavored milk-based beverages.     

Stringent delineation of Pallister-Hall syndrome in two long surviving patients: importance of radiological anomalies of the hands

We report two unrelated, long surviving patients (2 and 17 years) with syndromal hypothalamic hamartoblastoma. Both showed mild facial dysmorphism (downward slanted palpebral fissures, ptosis, microretrognathia), cleft epiglottis, and developmental delay. The younger child had stenosis of the pulmonary arteries, complex urogenital malformations, and anal atresia. In the oldest patient, the hamartoma caused precocious puberty of the central type, combined with complete hGH deficiency. Both patients showed bony anomalies of the extremities: variable proximal synostosis between central (2nd to 4th) metacarpals or intercalary polydactyly with generalised brachydactyly, severe brachytelephalangism, syndactyly, and nail hypoplasia. Together with the absence of anomalies of cholesterol metabolism, a combination of oral frenula, laryngeal malformations, digestive abnormalities, intercalary polysyndactyly, generalised brachytelephalangism, and nail hypoplasia should allow the delineation of Pallister-Hall syndrome, even when a CNS tumour is absent. The radiological abnormalities are helpful in differentiating Pallister-Hall syndrome from the other syndromes in which hypothalamic hamartoblastoma is observed. This is of major importance for genetic counselling, since Pallister-Hall syndrome may be a dominantly inherited disorder, thus contrasting with most of the other disorders with the CAVE phenotype, which are recessively inherited.