[Show abstract][Hide abstract]ABSTRACT: We probe the mechanisms at work in the build-up of thermoreversible gel
networks, with the help of hybrid gelatin gels containing a controlled density
of irreversible, covalent crosslinks (CL), which we quench below the physical
gelation temperature. The detailed analysis of the dependence on covalent
crosslink density of both the shear modulus and optical activity evolutions
with time after quench enables us to identify two stages of the physical
gelation process, separated by a temperature dependent crossover modulus: (i)
an early nucleation regime during which rearrangements of the triple-helix CL
play a negligible role, (ii) a late, logarithmic aging one, which is preserved,
though slowed down, in the presence of irreversible CL. We show that aging is
fully controlled by rearrangements and discuss the implication of our results
in terms of the switch from an early, local dynamics to a late, cooperative
[Show abstract][Hide abstract]ABSTRACT: Gelatin gels, permanently cross-linked following two different routes, exhibit the same phenomenology in which their turbidity builds-up in concert with their elastic modulus. This is analyzed in terms of a minimal model for the chemo-osmotic coupling mechanism first proposed by Bastide and Candau (in: “Physical Properties of Polymeric Gels”, J.-P. Cohen Addad Ed., J. Wiley & Sons, New York 1996). The analysis points out the important role of labile counterions, which usually stiffen (osmotically) the gel, thereby hindering the coupling. This might be the reason why this a priori generic mechanism was not observed earlier.
[Show abstract][Hide abstract]ABSTRACT: We present an extensive study of the enzyme-mediated, isothermal formation of covalently cross-linked gelatin gels. We find that the enzymatic activity in the forming network is drastically reduced compared with that in solution, and show that this can be attributed to the growing level of cross-link induced geometric constraints which impede translational and rotational motions. Thanks to the slowness of these kinetics, we monitor the concomitant build-up of the shear modulus G′ and of the optical turbidity , which indicates that gelation is associated with the development of a high level of inhomogeneity. We find that, as the gelatin concentration cG is varied, the levels of G′ and are strongly anti-correlated. Moreover, the lower cG, the more precocious the emergence of . We are able to analyze inhomogeneity development in terms of the amplification of structural fluctuations via the coupling between the kinetics of the cross-linking reaction and the osmotic flow driven by swelling pressure fluctuations. We expect this positive feedback mechanism to be efficient in any slow, irreversible gelation process.
[Show abstract][Hide abstract]ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder for which the research of new treatments is highly challenging. Since the fibrillogenesis of amyloid-β peptide 1-42 (Aβ(1-42)) peptide is considered as a major cause of neuronal degeneration, specific interest has been focused on aromatic molecules for targeting this peptide. In this paper, the synthesis of selegiline-functionalized and fluorescent poly(alkyl cyanoacrylate) nanoparticles (NPs) and their evaluation for the targeting of the Aβ(1-42) peptide are reported. The synthetic strategy relied on the design of amphiphilic copolymers by tandem Knoevenagel-Michael addition of cyanoacetate derivatives, followed by their self-assembly in aqueous solutions to give the corresponding NPs. Different cyanoacetates were used: (i) hexadecyl cyanoacetate (HDCA) to form the hydrophobic core of the NPs; (ii) rhodamine B cyanoacetate (RCA) for fluorescent purposes; (iii) methoxypoly(ethylene glycol) cyanoacetate (MePEGCA) for stealth properties and (iv) selegiline-poly(ethylene glycol) cyanoacetate (SelPEGCA) to obtain the desired functionality. Two different amphiphilic copolymers were synthesized, a selegiline-containing copolymer, P(MePEGCA-co-SelPEGCA-co-HDCA), and a rhodamine-labelled counterpart, P(MePEGCA-co-RCA-co-HDCA), further blended at variable ratios to tune the amount of selegiline moieties displayed at the surface of the NPs. Optimal formulations involving the different amphiphilic copolymers were determined by the study of the NP colloidal characteristics. Interestingly, it was shown that the zeta potential value of the selegiline-functionalized nanoparticles dramatically decreased, thus emphasizing a significant modification in the surface charge of the nanoparticles. Capillary electrophoresis has then been used to test the ability of the selegiline-functionalized NPs to interact with the Aβ(1-42) peptide. In comparison with non functionalized NPs, no increase of the interaction between these functionalized NPs and the monomeric form of the Aβ(1-42) peptide was observed, thus highlighting the lack of availability of the ligand at the surface of the nanoparticles. A mechanism explaining this result has been proposed and was mainly based on the burial of the hydrophobic selegiline ligand within the nanoparticles core.
Article · Sep 2011 · International Journal of Pharmaceutics
[Show abstract][Hide abstract]ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the extracellular deposition of amyloid-β peptides (Aβ). During the past few years, promising approaches based on nanotechnologies have emerged to alter Aβ aggregation and its related toxicity. This study aims to investigate the influence of the nanoparticle colloidal properties over the interaction with Aβ peptide 1-42 (Aβ(1-42)). Using capillary electrophoresis with laser-induced fluorescence detection, it was shown that biodegradable poly(ethylene glycol)-block-polylactide (PEG-b-PLA) nanoparticles were able to interact with Aβ(1-42) peptide leading to its uptake in rather short time periods. In addition, we highlighted the crucial role of the nanocarrier colloidal properties on the uptake kinetics. Whereas nanoparticles stabilized by sodium cholate (lower size and higher negative surface charge) gave optimum uptake kinetics, nanoparticles stabilized with others surfactants presented lower interactions. In contrast, PEG density seemed to have no influence on the interaction when sodium cholate was used for the preparation. This study intends to give new insights into Aβ(1-42) peptide interaction with nanoparticulate systems by helping to determine suitable nanoparticle characteristics regarding forthcoming therapeutic strategies against AD.
Full-text Article · Jul 2011 · Journal of Biotechnology