Biomedical subjects

D Bazile

Publications and source records attributed to D Bazile.

9 recordsLinked to original sources

PubMed1996

Effect of PEO surface density on long-circulating PLA-PEO nanoparticles which are very low complement activators.

The rapid uptake of injected nanoparticles by cells of the mononuclear phagocytes system (MPS) is a major obstacle when a long blood circulation time is needed. Whereas nanoparticles made from PLA and stabilized by surfactants (PLA-F68) are rapidly phagocytized, the rate of phagocytosis is strongly reduced in case of nanoparticles made from a diblock copolymer (PLA-PEO). Because of the role of the complement system in opsonization, this difference of phagocytosis was hypothesized to be related to this system. An important complement consumption was obtained in 5 min in the presence of PLA-F68 particles. In the presence of a higher surface area of PLA-PEO particles possessing a high PEO surface density, the consumption remained very low. When the average PEO surface density was decreased on such particles below a given threshold, a fast and strong complement consumption occurred again. These experimental data support the concept of steric repulsion towards proteins, by surfaces covered with terminally attached PEO chains and emphasize the prime importance of PEO surface density in such an effect. The major, but probably not exclusive, role of complement as an opsonin capable of inducing a fast phagocytosis by MPS should be taken into account concerning the in vitro evaluation of nanoparticles as candidates for a long blood circulation.

Biocompatible Materials↗

PubMed1995

Stealth Me.PEG-PLA nanoparticles avoid uptake by the mononuclear phagocytes system.

Nanoparticles were prepared from methoxy poly(ethylene glycol)poly(d,l-lactic acid) block copolymers (Me.PEG-PLA) or blends of Me.PEG-PLA and PLA by the precipitation-solvent diffusion method. These nanoparticles, labeled by introducing [14C]PLA in the formulation, were shown to be more slowly captured by cultured THP-1 monocytes than F68-coated PLA nanoparticles, in a PEG chain-length-dependent manner. In vivo, the half-life in plasma of the Me.PEG-PLA nanoparticles that were intravenously administered to rats is increased by a factor 180 compared with the F68-coated PLA nanoparticles. This mononuclear phagocytes system avoidance was explained according to a conformation model in which the PEG density at the surface of the particles is a key parameter.

Animals↗

PubMed1993

Adsorption/desorption of human serum albumin at the surface of poly(lactic acid) nanoparticles prepared by a solvent evaporation process.

Biocompatible and biodegradable nanoparticles of poly(lactic acid) (100% L-lactic units = PLA) were prepared by an emulsion, microfluidization, and solvent evaporation method using human serum albumin (HSA) as a surface agent. A radiolabeling technique was employed to quantify the serum albumin bound to the nanoparticles and to measure its desorption kinetics in various media at 22 degrees C and 37 degrees C (phosphate buffer pH 7.4, serum albumin 40 g/L in phosphate buffer pH 7.4 and fetal calf serum). The amount of serum albumin bound to the nanoparticles was found to be a linear function of 1/D (where D is the nanoparticle mean diameter) and was related to the total developed area of the nanoparticles. The adsorption/desorption behavior of serum albumin at the surface of the nanoparticles suggested a multilayer adsorption model. Moreover, a part of the serum albumin molecules was irreversibly bound regardless of the incubation conditions. Consequently, the classical Langmuirian theories of equilibria could not be applied.

Adsorption↗

PubMed1990

Structural features associated with alpha- anomeric in oligo-alpha-thymidylates.

Comparison between gel electrophoresis migrations of oligo-alpha-thymidylates and oligo-beta-thymidylates indicates that the migration of alpha-oligonucleotides under native conditions is different from the migration of beta-oligonucleotides when the number of thymines, part of the sequence, is higher than 5. Such difference disappears when the gels are run under denaturing conditions. This, together with UV spectra, indicates that the structure of alpha-oligonucleotides is more organized than the structure of beta-oligonucleotides and that such an organisation appears for a length higher than 5 monomeric units.

Electrophoresis, Polyacrylamide Gel↗

PubMed1989

alpha-DNA X: alpha and beta tetrathymidilates covalently linked to oxazolopyridocarbazolium (OPC): comparative stabilization of oligo beta-[dT]:oligo beta-[dA] and oligo alpha-[dT]:oligo beta-[dA] duplexes by the intercalating agent.

The influence of the intercalating oxazolopyridocarbazolium (HOPC) on the stabilization of modified oligonucleotides: alpha-T4c5OPC or beta-T4c5OPC associated to beta-oligo (dA) was studied. It appears that the situation is different from what has been observed for the interaction of these modified oligonucleotides with poly (rA). The higher free energy of formation of the alpha-T4c5OPC :beta-oligo(dA), when compared to beta-T4c5OPC, is essentially due to the overall stability added to this system by the intercalator. This enhanced stability comes from a higher number of binding sites of HOPC for the alpha:beta duplex together with a lower van't Hoff energy of formation of the alpha:beta duplex.

Carbazoles↗

PubMed1989

Alpha-DNA VIII: thermodynamic parameters of complexes formed between the oligo-alpha-deoxynucleotides: alpha-d(GGAAGG) and alpha-d(CCTTCC) and their complementary oligo-beta-deoxynucleotides: beta-d(CCTTCC) and beta-d(GGAAGG) are different.

The temperature dependence of the formation of a complex between an alpha-d(CCTTCC) hexanucleotide and its complementary beta-d(GGAAGG) sequence was studied and compared to the formation of the beta-d(CCTTCC):beta-d(GGAAGG) complex. Such alpha-beta complex is more stable than the regular beta:beta complex. The Tm value for the alpha:beta complex is 28 degrees C (delta G degrees = -7.3 kcal/mole) while Tm = 20, 1 degree C (delta G degrees = -6.3 kcal/mole) for the beta:beta complex. The stoechiometry of the alpha:beta complex corresponds to the formation of a 1:1 duplex. However, when the alpha- strand is made of alpha-purines: alpha-d(GGAAGG), the stability of the alpha:beta complex, alpha-d(GGAAGG):beta-d(CCTTCC) is found to be lower (Tm = 13.8 degrees C) than the stability of the regular beta-beta complex, leading to the conclusion that the nature of the alpha-sequence is important in terms of stability when considering the synthesis of such a sequence for using it as antisense oligonucleotide.

Base Composition↗

PubMed1989

Voltage-dependent introduction of a d[alpha]octothymidylate into electropermeabilized cells.

DC-3F cells were submitted to electric square wave pulses in the presence of a d[alpha]octothymidylate 32P labelled in the 5' position. Radioactivity was incorporated in a voltage-dependent manner and reached a maximum for a field intensity of 1300-1400 V.cm-1. Growth curves and parallel cloning efficiency experiments indicated that cell viability was not altered by electric pulses, alone or in the presence of the oligothymidylate, below a field intensity of 1300 V.cm-1. Using affinity chromatography we extracted the incorporated oligonucleotide and showed that it was not degraded during the electropermeabilization experiment time.

Animals↗

PubMed1988

Poly(rA) binding of alpha-anomeric and beta-anomeric tetrathymidylates covalently linked to an intercalating oxazolopyridocarbazolium. Determination of the binding parameters.

We have investigated by means of absorbance measurements at 310 nm the binding of alpha-anomeric or beta-anomeric tetrathymidylates covalently substituted at their 3' end by an intercalating agent (oxazolopyridocarbazolium), to poly(rA). Taking into account the strong autoaggregation of the free ligands, we have derived the binding parameters corresponding to the [alpha] and the [beta] ligands. The affinity of the alpha-anomer for poly(rA) is higher than the affinity of the beta-anomer in accordance with the Tm studies conducted on such a system.

Alkaloids↗

PubMedDate not supplied

An ellipticine derivative (oxazolopyridocarbazolium) 3' linked to tetrathymidylate stacks intramolecularly with the nearest thymine at low concentration and head-to-tail intermolecularly at high concentration.

The solution conformation of a tetrathymidylate linked through an ester bond to an ellipticine derivative oxazolopyridocarbazolium (OPC) at the 3' position was investigated using one- and two-dimensional nmr experiments. Since the total electric charge of the OPC ring may influence self-association, we first determined the pKa of the oxazole cyclic acidic function. Nuclear Overhauser effect spectroscopy experiments showed that, at low concentration, the OPC stacks intramolecularly with the nearest thymine at the 3' end. At highest concentration, however, the OPC rings are self-associated. The stacking constant was calculated using 1H chemical shift dilution experiment. The conformational model suggested by P-nmr was tested by molecular mechanics computations.

Alkaloids↗