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R Gref

Publications and source records attributed to R Gref.

30 records · Page 2Linked to original sources
PubMed1998

Protein encapsulation within polyethylene glycol-coated nanospheres. I. Physicochemical characterization.

The development of injectable nanoparticulate "stealth" carriers for protein delivery is a major challenge. We have shown the possibility of entrapping human serum albumin (HSA) in polyethylene glycol (PEG)-coated monodisperse biodegradable nanospheres with a mean diameter of about 200 nm, prepared from amphiphilic diblock PEG-polylactic acid (PLA) copolymers, with loadings up to 9% (w/w). Microscopic techniques and surface analysis studies enabled us to prove that the protein was well entrapped and not adsorbed onto the particle surface. Zeta potential and water uptake studies corroborated that part of the PEG chains are located in the nanosphere matrix. Water uptake in the nanospheres was related to their chemical composition, i.e., the respective wt% of PEG and PLA in the matrix, and not on their fabrication procedure. The hydrophilic PEG blocks absorbed up to 130% (w/w) water, whereas PLA absorbed only about 10% (w/w). However, the rate of swelling at the beginning of the process was related to the structure of the matrix, more particularly to the manner in which PEG was disposed at the surface. Furthermore, it was shown that the PEG "brush" at the nanosphere surface drastically reduces HSA adsorption on the PEG-PLA nanospheres compared to the PLA ones.

Adsorption↗
PubMed1998

Stealth PLA-PEG nanoparticles as protein carriers for nasal administration.

PURPOSE: The aim of the study was to encapsulate a model protein antigen, tetanus toxoid (TT), within hydrophobic (PLA) and surface hydrophilic (PLA-PEG) nanoparticles and to evaluate the potential of these colloidal carriers for the transport of proteins through the nasal mucosa. METHODS: TT-loaded nanoparticles, prepared by a modified water-in-oil-in-water solvent evaporation technique, were characterized in their size, zeta potential and hydrophobicity. Nanoparticles were also assayed in vitro for their ability to deliver active antigen for extended periods of time. Finally, 125I-TT-loaded nanoparticles were administered intranasally to rats and the amount of radioactivity recovered in the blood compartment, lymph nodes and other relevant tissues was monitored for up to 48 h. RESULTS: PLA and PLA-PEG nanoparticles had a similar particle size (137-156 nm) and negative surface charge, but differed in their surface hydrophobicity: PLA were more hydrophobic than PLA-PEG nanoparticles. PLA-PEG nanoparticles, especially those containing gelatine as an stabilizer, provided extended delivery of the active protein. The transport of the radiolabeled protein through the rat nasal mucosa was highly affected by the surface properties of the nanoparticles: PLA-PEG nanoparticles led to a much greater penetration of TT into the blood circulation and the lymph nodes than PLA nanoparticles. Furthermore, after administration of 125I-TT-loaded PLA-PEG nanoparticles, it was found that a high amount of radioactivity persisted in the blood compartment for at least 48 h. CONCLUSIONS: A novel nanoparticulate system has been developed with excellent characteristics for the transport of proteins through the nasal mucosa.

Administration, Intranasal↗
PubMed1997

The protective effect of zinc on rosin and resin acid toxicity in human polymorphonuclear leukocytes and human gingival fibroblasts in vitro.

Combinations of rosin and zinc are used in dentistry as components of periodontal dressings and cements and as root canal sealers. The composition and properties of rosins differ largely depending on source and refinement processes. Rosin (colophony) is composed of approximately 70% resin acids. In order to study the toxic effects of different natural rosins and purified resin acids and the detoxifying effects of zinc, these compounds were analyzed and tested on human polymorphonuclear leukocytes (PMN cells) and human gingival fibroblasts using the radiochromium release method. The rosins and the pure resin acids showed a strong dose-related cytotoxicity, which was inhibited by increased zinc concentrations. The purified resin acids (isopimaric, levopimaric, and neoabietic acid) were more toxic than the natural rosins. The contents of these resin acids might explain the difference in toxicity of the rosins tested. It is concluded that rosin and zinc are not to be considered inert compounds and that the cytoprotective effects of zinc and its role in dentistry products merit further investigations.

Adult↗
PubMed1997

Erosion of biodegradable block copolymers made of poly(D,L-lactic acid) and poly(ethylene glycol).

Biodegradable block copolymers made of poly(ethylene glycol) monomethylether (Me.PEG) and poly(D,L-lactic acid) (PLA) were investigated for their erosion properties. Wide angle X-ray diffraction (WAXD) and differential scanning calorimetry (DSC) investigations prior to erosion revealed that despite the low content of crystallizable Me.PEG of 10%, Me.PEG5-PLA45 is a partially crystalline polymer. The erosion of the polymer was investigated using cylindrical polymer matrix discs with a diameter of 8 mm and a height of 1.5 mm. WAXD and DSC spectra obtained from eroded polymer matrix discs suggest that both polymer blocks separate completely during erosion. The crystallinity of Me.PEG5-PLA45 was found to increase during erosion, which is probably due to the improved mobility of Me.PEG inside the polymer with a progressive degree of degradation. The erosion kinetics were found to be similar to that of PLA or poly(lactic-co-glycolic acid). During erosion the polymer matrix weight of dried samples remains constant for 11 weeks after which erosion sets in rapidly. From this observation one can conclude that the impact of the relatively small Me.PEG chains on Me.PEG5-PLA45 erosion is not pronounced. This is beneficial for all those applications that require the stability of the polymer matrix and in which the Me.PEG chain is intended to bring about other effects such as the modification of the surface properties of PLA polymers.

Biocompatible Materials↗
PubMed1996

Toxic effects of some conifer resin acids and tea tree oil on human epithelial and fibroblast cells.

The present study was undertaken to assess and compare the in vitro cytotoxic effects of three resin acid analogues: dehydrobietic acid, podocarpic acid, O-methylpodocarpic acid; an essential oil from Australia (tea tree oil); and tapped oleoresin from Thailand, on human epithelial and fibroblast cells, using a quantitative neutral red spectrophotometric assay. All of the investigated compounds except for tea tree oil exhibited a cytotoxic activity which was proportional to their concentrations and time of exposure up to 24 h, i.e. higher concentrations and longer time of exposure caused increased cell death. Dehydroabietic acid and the oleoresin were the most toxic compounds followed by O-methylpodocarpic acid, whereas podocarpic acid and tea tree oil showed a lower level of toxicity. On the basis on these findings it is concluded that an isopropyl group on the aromatic C-ring is of great importance for the cytotoxicity of the tested abietane resin acids, thus indicating that the cytotoxic activity of oleoresins most probably is caused by synergistic or additive effects of resin acids. The results from this work support the view that antibacterial activity parallels cytotoxic activity which suggests a similar mode of action, most probably exerted by membrane-associated reactions.

Abietanes↗
PubMed1995

Antimicrobial screening of zinc in the absence or presence of oleoresins and various resin acids.

Zinc and oleoresins are the main components of several wound dressings, and are also frequently used in root canal treatment. The in vitro antibacterial effects of zinc, six highly purified resin acids and two commercial oleoresins alone or combined in varying proportions were analysed. Oleoresins are composed of approximately 90% resin acids and the most common acids were included in this study. The antibacterial activity of the various chemicals was estimated using a Bioscreen robot analyser, which allowed 24 h kinetic documentation of bacterial growth. The bacteria employed were reference species commonly occurring on human skin or of oral origin. Zinc as well as the oleoresins and the pure resin acids all showed antibacterial activity when present in growth media, but the sensitivity of the bacteria varied. The presence of resin acids and oleoresins increased the antibacterial effect of zinc to varying degrees depending on the combination and the bacterial species tested. The results of the present study indicate that zinc, resin acids, or oleoresins alone, as well as combined, show antibacterial activity against selected aerobic Gram-positive and anaerobic Gram-negative bacteria.

Abietanes↗
PubMed1994

Biodegradable long-circulating polymeric nanospheres.

Injectable nanoparticulate carriers have important potential applications such as site-specific drug delivery or medical imaging. Conventional carriers, however, cannot generally be used because they are eliminated by the reticulo-endothelial system within seconds or minutes after intravenous injection. To address these limitations, monodisperse biodegradable nanospheres were developed from amphiphilic copolymers composed of two biocompatible blocks. The nanospheres exhibited dramatically increased blood circulation times and reduced liver accumulation in mice. Furthermore, they entrapped up to 45 percent by weight of the drug in the dense core in a one-step procedure and could be freeze-dried and easily redispersed without additives in aqueous solutions.

Animals↗
PubMed1993

The relationship between crown size and ring width in Pinus sylvestris L. stems: dependence on indole-3-acetic acid, carbohydrates and nitrogen in the cambial region.

Indole-3-acetic acid (IAA), carbohydrates, total nitrogen and amino acids in the cambial region and bark were measured at the top (10-year-old internode) and bottom (1.3 m) of the main stem of 50-year-old Pinus sylvestris L. trees, having different rates and longitudinal gradients of annual ring width formation. The trees were sampled during the most active period of wood production (June 23, July 15) and at the end of this period (August 23). Trees with a small crown and relatively slow growth rate (S-trees) were compared with trees in the same stand that had a large crown and fast growth rate (F-trees) as a result of thinning and fertilization. The effect of bottom pruning fast-growing trees (pruned F-trees) was also investigated. The F-trees had greater wood production than the S-trees at both the stem top and bottom. The difference was larger at the stem bottom, thus the relative decrease in ring width down the stem was steeper in the S-trees. The amount of sucrose and IAA per cm(2) in cambial region tissues was higher in F-trees than in S-trees. However, the differences in annual ring width between treatments and within trees were not reflected in the concentrations (expressed per gram fresh weight) of these substances, measured either in differentiating xylem, the cambium plus phloem, or in the cambial region as a whole. The concentrations of total nitrogen and amino acids were slightly higher in the F-trees than in the S-trees. Pruning the F-trees reduced wood production, particularly at the stem bottom, inhibited the springtime increase in starch, and decreased the amounts of sucrose and IAA per cm(2) in the cambial region. However, it was evident that the concentrations of sucrose, IAA, amino acid and nitrogen in the cambial region were not related to ring width. During June and July, the concentrations of these substances were generally higher at the stem bottom in the pruned F-trees than in the F-trees. The results provide evidence that it is the activity of the cambium rather than the availability of carbohydrates that determines the allocation of wood production along the tree stem. The results also indicate that tracheid production is not directly related to the IAA concentration in the cambial region.

Journal Article↗
PubMed1991

Antibacterial effects of zinc oxide, rosin, and resin acids with special reference to their interactions.

The growth inhibiting capacity of zinc oxide combined with ordinary rosin (Portuguese rosin), abietic acid or dehydroabietic acid was studied using two different methods. To mimic the actual treatment of wounds, circular tapes or sensitivity discs were placed on Müller-Hinton-agar plates that had been seeded with various facultative aerobic bacteria, and the zones of inhibition were measured. The agar dilution method was used to measure the minimum inhibitory concentration (MIC). Inhibition of growth was restricted to Gram-positive facultative aerobic bacteria for the individual substances zinc oxide, Portuguese rosin, or resin acids, as well as for combinations of these. In general the combination of zinc oxide and dehydroabietic acid was a more potent antibacterial substance than the corresponding combination of zinc with rosin or abietic acid. These combinations commonly had synergistic antibacterial effects.

Abietanes↗
PubMed1990

Inhibitory effect of zinc oxide on contact allergy due to colophony.

Contact allergy to a wound dressing with an adhesive mass consisting of colophony, zinc oxide and rubber (Mezinc) was studied in 179 patients with a history of eczema. 12 patients were found to be allergic to colophony, whereas only 4 of these patients also showed a positive patch test reaction to the wound dressing. 14 patients with verified moderate contact allergy to colophony were patch tested with adhesive mass (10%), Portuguese colophony (10%), zinc oxide (10%), purified resin acids (10%), and Portuguese colophony (10%), in combination with zinc oxide. Only 3 patients reacted to the adhesive mass, whereas all patients showed a positive patch test reaction to Portuguese colophony. A combination of zinc oxide (10%) with Portuguese colophony (10%) provoked a positive patch test reaction in only 5 of these 14 patients. An allergic reaction to abietic acid (90-95% purity) was found in 7 patients and to neoabietic acid (99 + %) in 3 patients, whereas no reactions to dehydroabietic (99 + %), isopimaric (99 + %) or levopimaric acids (98 + %) were found.

Adult↗
PubMed1990

Antibacterial activity of rosin and resin acids in vitro.

The antibacterial effects of rosins and resin acids were studied in vitro using three methods, disc diffusion on agar, agar dilution, and broth dilution. Rosin and some resin acids had antibacterial effects that were restricted to Gram-positive bacteria. The abietic type of acids had a more pronounced antibacterial activity than the pimaric and labdane acids when the disc diffusion method was used but there was no inhibition of growth of Gram-negative bacteria. Among the individual resin acids, dehydroabietic acid was generally the most potent, when disc diffusion on agar was used, and prediffusion increased the inhibitory effect. The composition of the pure resin acids dehydroabietic, neoabietic, and isopimaric acid did not change during the experiment, but abietic and levopimaric acid were converted into dehydroabietic acid by the addition of Müller-Hinton agar. In conclusion the old tradition of treating wounds with pitch, sap, rosin, or rosin containing tapes might therefore have some antibacterial relevance.

Bacteria↗