Domenico Lombardo

Temperature-induced micelle to vesicle transition: kinetic effects in the DMPC/NaC system

The formation of spherical and monodisperse small unilamellar vesicles is observed upon temperature jumps in a mixed system composed of a phospholipid (dimyristoylphosphatidylcholine) and a bile salt (sodium cholate) in an aqueous buffer. In order to enhance the X-ray contrast of the system a mixed water/sucrose buffer is used. The spontaneous formation of unilamellar structures from mixed micelles upon temperature increase and the reverse solubilisation of membranes upon cooling is studied by means of synchrotron radiation small-angle X-ray scattering. The variations of the vesicle size are presented when the temperature and the surfactant / lipid ratio are modified. The kinetic conditions leading to monodisperse vesicles as well as the reversibility of the micelle to vesicle transition are investigated.

Scaling properties in the internal structure of dendrimer systems

In this work, we study the internal density distribution in a dendrimer or “starburst polymers” system at different generations. We have used different techniques like small angle X-ray scattering, quasi-elastic light scattering and a Molecular dynamics simulation. Obtained data, compared with the literature ones, proposed that lower generation dendrimers display an internal self-similar structure, whereas the higher generations tend to exhibit a spherical homogenous dense structure.

Glass and percolation transitions in dense attractive micellar system

In this work, we study a copolymer-micellar system characterized by clustering processes due to a short-range attractive interaction. This originates a percolation process and a new type of kinetic glass transition. We have studied these intriguing dynamical situations by means of an extensive set of light scattering and viscoelasticity experiments. Obtained data, in both the phenomena, are accounted for by considering in a proper way fractal clustering processes and the related scaling concepts. Near the percolation line the main role in the system structure and dynamics is played by the clusters partial screening of hydrodynamic interaction, that behaves, on approaching the percolation threshold, dramatic effects on the rheological properties and on the density decay relaxations. The ergodic–nonergodic transition line (glass transition) is studied in terms of the intermediate scattering functions (ISF) in the frame of the mode coupling theory. The measured ISF gives evidence of a logarithmic decay on the density fluctuation followed by a power law behavior. This latter phenomenon is the signature of a high-order glass transition of the A3 type (cusp-like singularity).

Effect of anionic and cationic polyamidoamine (PAMAM) dendrimers on a model lipid membrane

In spite of the growing variety of biological applications of dendrimer-based nanocarriers, a major problem of their potential applications in bio-medicine is related to the disruption of lipid bilayers and the cytotoxicity caused by the aggregation processes involved onto cellular membranes. With the aim to study model dendrimer-biomembrane interaction, the self-assembly processes of a mixture of charged polyamidoamine (PAMAM) dendrimers and dipalmitoylphosphatidylcholine (DPPC) lipids were investigated by means of Zeta potential analysis, Raman and x-ray scattering. Zwitterionic DPPC liposomes showed substantially different behaviors during their interaction with negatively charged (generation G=2.5) sodium carboxylate terminated (COO- Na+) dendrimers or positively charged (generation G=3.0) amino terminated (-NH2) dendrimers. More specifically the obtained results evidence the sensitive interactions between dendrimer terminals and lipid molecules at the surface of the liposome, with an enhancement of the liposome surface zeta potential, as well as in the hydrophobic region of the bilayers, where dendrimer penetration produce a perturbation of the hydrophobic alkyl chains of the bilayers. Analysis of the SAXS structure factor with a suitable model for the inter-dendrimers electrostatic potential allows an estimation of an effective charge of 15 ǀeǀ for G=2.5 and 7.6 ǀeǀ for G=3.0 PAMAM dendrimers. Only a fraction (about 1/7) of this charge contributes to the linear increase of liposome zeta-potential with increasing PAMAM/DPPC molar fraction. The findings of our investigation may be applied to rationalize the effect of the nanoparticles electrostatic interaction in solution environments for the design of new drug carriers combining dendrimeric and liposomal technology.

Soft Interaction in Liposome Nanocarriers for Therapeutic Drug Delivery

The development of smart nanocarriers for the delivery of therapeutic drugs has experienced considerable expansion in recent decades, with the development of new medicines devoted to cancer treatment. In this respect a wide range of strategies can be developed by employing liposome nanocarriers with desired physico-chemical properties that, by exploiting a combination of a number of suitable soft interactions, can facilitate the transit through the biological barriers from the point of administration up to the site of drug action. As a result, the materials engineer has generated through the bottom up approach a variety of supramolecular nanocarriers for the encapsulation and controlled delivery of therapeutics which have revealed beneficial developments for stabilizing drug compounds, overcoming impediments to cellular and tissue uptake, and improving biodistribution of therapeutic compounds to target sites. Herein we present recent advances in liposome drug delivery by analyzing the main structural features of liposome nanocarriers which strongly influence their interaction in solution. More specifically, we will focus on the analysis of the relevant soft interactions involved in drug delivery processes which are responsible of main behaviour of soft nanocarriers in complex physiological fluids. Investigation of the interaction between liposomes at the molecular level can be considered an important platform for the modeling of the molecular recognition processes occurring between cells. Some relevant strategies to overcome the biological barriers during the drug delivery of the nanocarriers are presented which outline the main structure-properties relationships as well as their advantages (and drawbacks) in therapeutic and biomedical applications.

Water dynamics in amphiphiles and alcoholic solutions

Light scattering studies of water properties in aqueous solutions of polyoxyethylene non-ionic amphiphiles C10E5 and methanol are presented. Depolarized Raylegh spectra are studied to obtain the rotational relaxational time of water, whereas Brillouin scattering is used to have details on the sound propagation. The systems are studied for different temperatures and concentrations. Data analysis reveals that the solutes (amphiphile and alcohol) molecular head groups (hydrophilic and hydrophobic) have relevant effects on the water dynamics and structure.

Small-angle X-ray scattering structural investigations of starburst dendrimers in solution

A series of polyamidoamine dendrimers (generations 1.5–4.0, with ethylenediamine as the central core) has been investigated in methanol solution by means of the small-angle X-ray scattering technique. The comparative analysis of the structural properties of integer and half-integer generations of the dendrimers seems to be dominated by rather different trends.

Structural Relaxation in Dense Microemulsions

Microemulsions, in the water in oil stable phase (w/o), constitute an interesting system for their different and important physical properties, where are involved in a direct way structural effects such as a critical behavior [1], a percolation phenomenon [2] and a glasslike transition for high-volume fractions of the dispersed phase [3]. This latter process has been studied with particular interest by means of different experimental techniques such as elastic and quasi-elastic light scattering experiments and Small Angle Neutron Scattering (S.A.N.S.) [4], since the microemulsion is a model system, togheter some polystyrene colloidal suspensions, for the analysis of the dynamics of high packed liquids. The packing fraction of the droplets, keeping their radius constant, can be easily changed up to very high water volume fractions. In these conditions the measured density correlation function shows deviations from an exponential decay and follows a stretched exponential form (Kohlrausch—Wi11iams—Watts). This behavior, that is typical of glass—forming systems, is accomplished by a dynamic slowing-down in the initial decay rate of the density correlation function.

Soft nanoparticles charge expression within lipid membranes: The case of amino terminated dendrimers in bilayers vesicles

Interactions of charged nanoparticles with model bio-membranes provide important insights about the soft interaction involved and the physico-chemical parameters that influence lipid bilayers stability, thus providing key features of their cytotoxicity effects onto cellular membranes. With this aim, the self-assembly processes between polyamidoamine dendrimers (generation G = 2.0 and G = 4.0) and dipalmitoylphosphatidylcholine (DPPC) lipids were investigated by means of Zeta potential analysis, x-rays, Raman and quasielastic light scattering experiments. Raman scattering data evidenced that dendrimers penetration produce a perturbation of the DPPC vesicles alkyl chains. A linear increase of liposome zeta-potential with increasing PAMAM concentration evidenced that only a fraction of the dendrimers effective charge contributes to the expression of the charge at the surface of the DPPC liposome. The linear region of the zeta-potential extends toward higher PAMAM concentrations as the dendrimer generation decreases from G = 4.0 to G = 2.0. Further increase in PAMAM concentration, outside of the linear region, causes a perturbation of the bilayer characterized by the loss in multilamellar correlation and the increase of DPPC liposome hydrodynamic radius. The findings of our investigation help to rationalize the effect of nanoparticles electrostatic interaction within lipid vesicles as well as to provide important insights about the perturbation of lipid bilayers membrane induced by nanoparticles inclusion.

Modeling of the particle scattering structure factor for branched bio-polymers in solution: A X-ray scattering study

We present a study which illustrates the modeling of the Particle Scattering Structure Factor from Small Angle X-ray Scattering (SAXS) data. The studied sample was a poly(amidoamine) Pamam dendrimers in water solution. The intra-particle form factor P(q) has been analyzed employing an inverse Fourier transformation which allows to obtain the particle pair distance distribution function and to gain information about dendrimer shape. The experimental inter-dendrimer structure factor S(q) has been analysed in the framework of liquid integral equation theory for charged systems in solution. From that, we derive an effective interparticle interaction composed of a screened Coulombic plus hard-sphere repulsion potential, which allow the estimation of the dendrimer effective surface charge Z eff . The present analysis, applied to a Pamam dendrimers in water solution, strongly supports the finding that structures and interaction of dendrimer is strongly influenced by charge effects. As a result, this quantity can be considered as a crucial parameters for the modulation of the degree of structural organization in solution, suitable for a number of potential applications.