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The exact moment approach (EMA) is adopted to predict, without any fitting parameters, the plate height curves for polystyrene microparticles of different sizes in micropillar array columns performed by hydrodynamic chromatography. The EMA allows us to decouple the contribution of horizontal and vertical dispersion terms and thus investigate the influence of pillar height and interpillar distance on separation performance. In the convection-controlled regime, we found that axial dispersion is mainly controlled by the vertical dispersion term, the latter being due to the flow-arresting top and bottom walls. This vertical contribution can be estimated from the axial dispersion in rectangular, open tubular channels formed between the pillars. Henceforth, plate height curves can be accurately predicted by simply adding the estimated vertical term to the horizontal dispersion term evaluated from 2D simulations. This finding allowed us to understand that, to improve separation performance, it is advisible to decrease the interpillar distance (expected result) and decrease the pillar height (counterintuitive result).
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We report on the possibility to extend to bi-continuous packings the two models for the effective longitudinal diffusion Deff, or B-term band broadening, recently proposed for discontinuous chromatographic beds. In bi-continuous packings, like monolithic columns, solutes experience a connected end-to-end pathway in both the mobile and stationary zones, as opposed to discontinuous packings, wherein the stationary adsorptive zone is distributed over a set of isolated elements. Since it is unclear whether a densely packed bed of spherical particles should be treated as a continuous or a bi-continuous medium, this extension is also crucial to fully understand the behaviour of packed particle beds. The proposed models for the effective longitudinal diffusion Deff originate from the adoption of the Two Zone Moment Analysis (TZMA) method by which Deff can be expressed as a linear combination of two essential quantities γm and γs, referred to as effective zone-diffusion factors. In the present work we propose two analytical models for γm and γs that now cover both the discontinuous and the bi-continuous case. To validate the theory, several bi-continuous packings are investigated, including the tetrahedral skeleton model (TSM), six different Triple Periodic Minimal Surface (TPMS) monoliths and randomly packed beds of spheres. For all of these, the models provide highly accurate results for Deff over a wide range of porosities and zone retention factors kâ³. The comparison with literature experimental data for both monolithic silica columns and columns packed with fully porous and porous-shell particles is also presented.
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Dióxido de Silicio , Cromatografía Liquida/métodos , Difusión , Porosidad , Adsorción , Dióxido de Silicio/químicaRESUMEN
We report on a steady-state based, and hence highly accurate numerical modelling study of the effect of the top and bottom wall in the current generation of micro-pillar array columns. These have a mesoporous retention layer that not only covers the pillar walls but also the bottom wall. Our results show that the performance of these columns can in general not be improved by also covering the top wall with the same layer, despite the increased column symmetry this approach would offer. The reason for this is that the local species retardation caused by a retentive layer is much stronger than the pure flow arresting effect of an uncovered wall. At least, this has a crucial impact in high aspect-ratio systems such as micro-pillar array columns because these require a small inter-pillar distance to promote mass transfer together with a large channel depth to enable a sufficiently high flow rate. On the other hand, a notable improvement could be made if micro-pillar array would be produced without having a retentive layer at the bottom. At Péclet number Pe = 50 and aspect ratio AR = 5 for flow-channels, this gain amounts up to about 4.5 h-units at a zone retention factor k'' = 2 and 1.75 h-units at k'' = 16 (gain scales almost linearly with Pe). To verify these results, we also considered another high aspect-ratio system with a simplified geometry: the open-tubular channel with a flat-rectangular cross-section. This led to very similar observations, thus confirming the findings for the micro-pillar array. The results produced in the present study also allow us to conclude that the classic modelling paradigm adopted in chromatography, which is based on the independency and hence additivity of the hCm- and hCs-contributions, can lead to large modelling errors in chromatographic systems with a high aspect-ratio, even when their geometry is so simple as that of a straight open-tubular channel with constant cross-section. Indeed, when both zones are treated independently, the analysis misses how the vertical diffusion through the retentive layer helps suppressing the vertical gradients in the mobile zone. The diffusion through this layer occurs in a ratio of k''Ds/Dm (Dm being the diffusion coefficient in mobile phase zone and Ds being the diffusion coefficient in stationary phase zone), such that at high retention factors this diffusion contribution even becomes the dominant one.
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Cromatografía , DifusiónRESUMEN
The two-zone moment-analysis method for the determination of the dispersion tensor in hierarchical retentive porous media has been adopted to compute and model the effective longitudinal diffusion Deff, or equivalently the B-term band broadening, in chromatographic beds filled with ordered porous particles. On the one hand, this approach offers accurate numerical results for Deff while keeping computational expenses low. On the other hand, it also gives direct insight for the analytical modelling, readily revealings the two main essential quantities (resp. referred to as the mobile-zone and stationary-zone effective diffusion factors γm and γs) that contribute to Deff. Modelling these two main parameters provided us with two new analytical models for Deff: a general one, valid for diluted and concentrated packings and accurate in the whole range of relevant intra-particle diffusion coefficient Dpz, and an approximate one, reliable for diluted packings and accurate also for concentrated packings with low to intermediate values of Dpz. The large advantage of both models is that they do not need any fitting parameter because all the required information is incorporated into the experimentally accessible geometric obstruction factor in the mobile phase originating from the tortuosity of the through-pore space (limiting case of fully solid particles without any retention). These models hence serve as an alternative to the Effective Medium Theory (EMT) models used so far in the literature. To validate the theory, five ordered geometries have been investigated. The accuracy of the general model proposed has been quantified and found to be comparable with that of the 3rd order approximate Torquato model for four geometries, even for macro-porosities close to the close-packing limit. The case of a 2-d triangular array of ellipsoidal particles with different elongations is also investigated to show the general validity and applicability of the models.
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Cromatografía , Porosidad , Cromatografía/métodos , DifusiónRESUMEN
We have investigated the possibility to establish a theoretical plate height expression for the band broadening in the most widely used micro-pillar array column format, i.e., a cylindrical pillar array wherein the pillar walls and the channel bottom are coated with a thin layer of mesoporous material. Assuming isotropic diffusion in the shell-layer, it was found that the vertical diffusive transport along the porous shell-layer covering the pillar walls significantly suppresses the band broadening originating from the vertical migration velocity gradients. As the vertical transport in the shell-layer increases linearly with the retention equilibrium constant K, this leads to an anomalous dependency on the retention factor. Indeed, instead of increasing with k'' and following the classic (1+ak''+bk''2)/(1 + k'')2-dependency governing a classic Taylor-Aris system, the variation of the mobile zone mass transfer resistance term hCm in a 3D pillar array with bottom-wall retention goes through a maximum (resp. factor 1.5 (k''=4) and 2 (k''=16) difference between observed and classic Taylor-Aris behaviour). This effect increases with increasing pillar heights and increasing reduced velocities. Because of this complex k''-dependency, it proves very cumbersome to establish a general plate height equation covering all conditions. Instead, a plate height expression was established that is limited up to k''=4, but remains accurate for higher k''-values for cases where the ratio of pillar height over inter-pillar distance remains below 5. It can however be anticipated the proposed analytical model is only valid in a rather limited range around the presently considered external porosity of ε=0.5.
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Porosidad , DifusiónRESUMEN
Using a two-zone moment analysis (TZMA) method based on Brenner's generalized dispersion theory for two-dimensional (2D) and three-dimensional (3D) periodic media, we investigated the mechanisms for dispersion in particulate media for liquid chromatography. This was done using a set of plate height data covering an unprecedented wide range of retention factors, diffusion coefficients, and velocities, all computed with unequaled accuracy. Applying Giddings' additivity test, based on alternatingly making the diffusion coefficient in the mobile and stationary zones infinitely large, the dispersion data clearly indicate a lack of additivity. Although this lack could be directly understood by identifying the existence of multiple parallel mass transfer paths, the additivity assumption interestingly overestimates the true C term band broadening (typically by more than 10%, depending on conditions and dimensionality of the system). However, Giddings originally asserted the occurrence of parallel paths would always lead to an underestimation of the dispersion. The origin of the lack of additivity is analyzed in detail and qualitatively explained. Finally, we also established a generic framework for the modeling of the effect of the reduced velocity and the retention coefficient on the C term in ordered chromatographic media. This led to the introduction of a new expression for the mobile zone mass transfer term, which, unlike the currently used literature expression, contains the complete kâ³ dependency.
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We report on a new homogenization approach to solve, with drastically improved speed and accuracy, the general advection-diffusion equation in hierarchical porous media with localized diffusion and adsorption/desorption processes, thus opening the way to a much deeper understanding of the band broadening process in chromatographic systems. The proposed robust and efficient moment-based approach allows us to compute the exact local and integral concentration moments and hence provides exact solutions for the effective velocity and dispersion coefficients of migrating solute particles. Innovative to the proposed method is also that it not only produces the exact effective transport parameters of the long-time asymptotic solution, but also their entire transient. The analysis of the transient behaviour can be used, for example, to properly identify the time and length scales needed to achieve the macro-transport conditions. If the hierarchical porous media can be represented as the periodic repetition of a unit lattice cell, the method only requires the solution of the time-dependent advection-diffusion equations for the zeroth order and first-order exact local moments, exclusively on the unit cell. This implies an enormous reduction of the computational efforts and a significant improvement of the accuracy of the results when compared to the direct numerical simulation (DNS) approaches which require flow domains that are long enough to achieve steady-state conditions, and hence often cover tens to hundreds of unit cells. The reliability of the proposed method is verified by comparing its predictions with DNS results, in one, two and three dimensions, in both transient and asymptotic conditions. The influence of top and bottom no-slip walls on the separation performance of chromatographic columns with micromachined porous and nonporous pillars is discussed in detail.
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Porosidad , Reproducibilidad de los Resultados , Difusión , Simulación por Computador , AdsorciónRESUMEN
Open-Tubular Liquid Chromatography (OTLC) is currently limited by two shortcomings, namely the low ratio of adsorbing area to the channel volume and the large values of the Height Equivalent of the Theoretical Plate (HETP) due to Taylor-Aris dispersion. Previous work focusing on axial dispersion of nonadsorbing solutes showed how it is possible to tame the Taylor-Aris effect by inducing transversal velocity components acting alongside the main pressure-driven axial flow. We here analyze the impact of transversal flow on the separation resolution in OTLC, where simultaneous equilibrium adsorption at the channel walls is superimposed to the analyte transport in the mobile phase. A three-dimensional steady flow generated by the combination of a pressure-driven flow and an electroosmotically-induced transversal flow is used as case study. Flows geometries possessing regular and chaotic streamlines are created by axially-invariant and periodically-alternate arrangements of the electrodes along the channel walls, respectively. By enforcing Brenner's macrotransport approach, we predict the column length achieving a prescribed level of resolution as a function of the Péclet number and of the species affinity towards the stationary adsorbing phase. Results show that the presence of transversal flows can lower sensitively the dependence of the column length on the Péclet number. Flows possessing chaotic streamlines prove the most efficient choice at large eluent velocities and low values of the column adsorption constant.
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Cromatografía Liquida , Cromatografía Liquida/métodos , AdsorciónRESUMEN
Taylor-Aris dispersion represents an undesired phenomenon in pressure-driven liquid chromatography, often responsible for the unchecked increase of the Height Equivalent of the Theoretical Plate (HETP) when high throughput operating conditions are sought. Previous work on the subject showed how it is possible to contain the augmented dispersion in empty microchannels by inducing cross-sectional velocity components yielding an overall helical structure of the flow streamlines. Here, we explore the possibility of further reducing axial dispersion by devising flow conditions that give rise to chaotic streamlines. A three-dimensional steady flow generated by the combination of a pressure-driven Poiseuille flow and an electroosmotically-induced spatially periodic flow is used as a case study. Brenner's macrotransport approach is used to predict the axial dispersion coefficient of a diffusing solute in flows possessing regular, partially chaotic and globally chaotic kinematic features. Accurate Lagrangian-stochastic simulations of particle ensembles are used to validate the predictions obtained through Brenner's paradigm. Our findings suggest that the Taylor-Aris phenomenon can be altogether suppressed in the limit of globally chaotic kinematics. A theoretical interpretation of this outcome is developed by combining macrotransport theory with established results of the spectral approach to mixing in advecting-diffusing chaotic flows.
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Estudios Transversales , Difusión , SolucionesRESUMEN
The dynamics of finite-sized particles with large inertia are investigated in steady and time-dependent flows through the numerical solution of the invariance equation, describing the spatiotemporal evolution of the slow/inertial manifold representing the effective particle velocity field. This approach allows for an accurate reconstruction of the effective particle divergence field, controlling clustering/dispersion features of particles with large inertia for which a perturbative approach is either inaccurate or not even convergent. The effect of inertia on heavy and light particles is quantified in terms of the rate of contraction/expansion of volume elements along a particle trajectory and of the maximum Lyapunov exponent for systems exhibiting chaotic orbits, such as the time-periodic sine-flow on the 2D torus and the time-dependent 2D cavity flow.
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Cystic fibrosis (CF) is a disease characterized by the production of viscous mucoid secretions in multiple organs, particularly the airways. The pathological increase of proteins, mucin and biological polymers determines their arrangement into a three-dimensional polymeric network, affecting the whole mucus and impairing the muco-ciliary clearance which promotes inflammation and bacterial infection. Thus, to improve the efficacy of the drugs usually applied in CF therapy (e.g., mucolytics, anti-inflammatory and antibiotics), an in-depth understanding of the mucus nanostructure is of utmost importance. Drug diffusivity inside a gel-like system depends on the ratio between the diffusing drug molecule radius and the mesh size of the network. Based on our previous findings, we propose the combined use of rheology and low field NMR to study the mesh size distribution of the sputum from CF patients. Specifically, we herein explore the effects of chest physiotherapy on CF sputum characteristic as evaluated by rheology, low field NMR and the drug penetration through the mucus via mathematical simulation. These data show that chest physiotherapy has beneficial effects on patients, as it favourably modifies sputum and enhances drug penetration through the respiratory mucus.
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Fibrosis Quística , Nanoestructuras , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/metabolismo , Humanos , Moco/metabolismo , Modalidades de Fisioterapia , Esputo/química , Esputo/metabolismoRESUMEN
In a recent article [Analytical Chemistry, 93(17), 6808-6816 (2021)], an unconventional device configuration enforcing a Brownian sieving mechanism was proposed as proof of concept for the efficient implementation of microcapillary hydrodynamic chromatography (MHDC). In this article, we perform a thorough analysis of the device geometry and of operating conditions, in order to single out the optimal configuration maximizing separation resolution. Brenner's macro-transport theory provides the technical picklock to perform the search for the optimum over a wide choice of device geometries and for a range of values of the particle Péclet number covering most conditions encountered in practical implementations of MHDC. Specifically, effective transport coefficients defining the dynamics of the suspended phase are obtained by the solution of a two-dimensional steady-state advection-diffusion equation defined onto the channel cross-section. The eigenvalue/eigenfunction structure of the associated transient problem is exploited in order to quantify the timescale for reaching the macro-transport regime conditions. Based on this timescale and on the effective transport parameters, an estimate of the column length necessary to achieve a prescribed level of separation resolution is obtained. We identify device geometry and operating conditions where the capillary length is shrunk down by a factor above ten compared to the standard MHDC configuration. Lagrangian stochastic statistics of particle ensembles are used to validate the results obtained through Brenner's macro-transport approach. The method proposed can be readily generalized to other classes of device geometries enforcing the same Brownian sieving mechanism.
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Cromatografía , Hidrodinámica , DifusiónRESUMEN
BACKGROUND: As most cystic fibrosis (CF) patients progress to respiratory failure, lung functionality assessment is pivotal. We previously developed a test that indirectly monitors airways (inflammation/functional test) by measuring the spin-spin relaxation time (T2m) of the water hydrogens present in CF sputum. Here the T2m significance in the monitoring of CF lung disease was further investigated by studying the correlation of T2m with: 1) sputum viscoelasticity, 2) mucociliary clearability index (MCI)/cough clearability index (CCI) and 3) sputum average mesh-size. METHODS: Sputum samples from 25 consenting CF subjects were analyzed by rheology tests (elastic modulus G and zero shear viscosity η0) and Low Field Nuclear Magnetic (LF-NMR) resonance (T2m). MCI/CCI were calculated from the rheological parameters. The average mesh-size (ξ) of the sputum structure was then evaluated by rheology/LF-NMR, together with FEV1 for each patient. RESULTS: There was an inverse correlation between G and η0 versus T2m, indicating that a worsening of the lung condition (T2m-FEV1 drop) is paralleled by an increase in sputum viscoelasticity (G and η0) favoring mucus stasis/inflammation. A direct correlation was also observed between T2m and MCI/CCI, showing that T2m provides information as to airway mucus clearing. Moreover, there was a direct correlation between T2m and the average sputum mesh size (ξ). CONCLUSIONS: We demonstrated a correlation between T2m (measured in CF patient's sputum) and the sputum viscoelasticity/average mesh-size and with MCI/CCI, parameters related to airway mucus clearing. Thus, the present data strengthen the potential of our test to provide indirect monitoring of airway disease course in CF patients as T2m depends on mucus solid concentration and nanostructure.
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Fibrosis Quística/fisiopatología , Espectroscopía de Resonancia Magnética , Reología , Adulto , Anciano , Anciano de 80 o más Años , Fibrosis Quística/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Depuración Mucociliar , Pruebas de Función Respiratoria , Esputo/química , ViscosidadRESUMEN
Microcapillary hydrodynamic chromatography (MHDC) is a well-established technique for the size-based separation of suspensions and colloids, where the characteristic size of the dispersed phase ranges from tens of nanometers to micrometers. It is based on hindrance effects which prevent relatively large particles from experiencing the low velocity region near the walls of a pressure-driven laminar flow through an empty microchannel. An improved device design is here proposed, where the relative extent of the low velocity region is made tunable by exploiting a two-channel annular geometry. The geometry is designed so that the core and the annular channel are characterized by different average flow velocities when subject to one and the same pressure drop. The channels communicate through openings of assigned cut-off length, say A. As they move downstream the channel, particles of size bigger than A are confined to the core region, whereas smaller particles can diffuse through the openings and spread throughout the entire cross section, therein attaining a spatially uniform distribution. By using a classical excluded-volume approach for modeling particle transport, we perform Lagrangian-stochastic simulations of particle dynamics and compare the separation performance of the two-channel and the standard (single-channel) MHDC. Results suggest that a quantitative (up to thirtyfold) performance enhancement can be obtained at operating conditions and values of the transport parameters commonly encountered in practical implementations of MHDC. The separation principle can readily be extended to a multistage geometry when the efficient fractionation of an arbitrary size distribution of the suspension is sought.
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Experiments on swelling and solute transport in polymeric systems clearly indicate that the classical parabolic models fail to predict typical non-Fickian features of sorption kinetics. The formulation of moving-boundary transport models for solvent penetration and drug release in swelling polymeric systems is addressed hereby employing the theory of Poisson-Kac stochastic processes possessing finite propagation velocity. The hyperbolic continuous equations deriving from Poisson-Kac processes are extended to include the description of the temporal evolution of both the Glass-Gel and the Gel-Solvent interfaces. The influence of polymer relaxation time on sorption curves and drug release kinetics is addressed in detail.
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A non-isothermal moving-boundary model for food dehydration, accounting for shrinkage and thermal effects, is proposed and applied to the analysis of intermittent dehydration in which air temperature, relative humidity, and velocity vary cyclically in time. The convection-diffusion heat transport equation, accounting for heat transfer, water evaporation, and shrinkage at the sample surface, is coupled to the convection-diffusion water transport equation. Volume shrinkage is not superimposed but predicted by the model through the introduction of a point-wise shrinkage velocity. Experimental dehydration curves, in continuous and intermittent conditions, are accurately predicted by the model with an effective water diffusivity Deff(T) that depends exclusively on the local temperature. The non-isothermal model is successfully applied to the large set of experimental data of continuous and intermittent drying of Rocha pears.
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Microfluidic separators based on Deterministic Lateral Displacement (DLD) constitute a promising technique for the label-free detection and separation of mesoscopic objects of biological interest, ranging from cells to exosomes. Owing to the simultaneous presence of different forces contributing to particle motion, a feasible theoretical approach for interpreting and anticipating the performance of DLD devices is yet to be developed. By combining the results of a recent study on electrostatic effects in DLD devices with an advection-diffusion model previously developed by our group, we here propose a fully predictive approach (i.e., ideally devoid of adjustable parameters) that includes the main physically relevant effects governing particle transport on the one hand, and that is amenable to numerical treatment at affordable computational expenses on the other. The approach proposed, based on ensemble statistics of stochastic particle trajectories, is validated by comparing/contrasting model predictions to available experimental data encompassing different particle dimensions. The comparison suggests that at low/moderate values of the flowrate the approach can yield an accurate prediction of the separation performance, thus making it a promising tool for designing device geometries and operating conditions in nanoscale applications of the DLD technique.
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Dispositivos Laboratorio en un Chip , Técnicas Analíticas Microfluídicas , Microfluídica , Electricidad EstáticaRESUMEN
Polymeric oral thin films (OTFs) were prepared by the casting method, combining gellan gum (GG), a water-soluble polysaccharide, and glycerol (Gly) as a plasticizing agent. GG-Gly films were investigated as potential systems for buccal drug delivery using fluconazole (Class I of the Biopharmaceutical Classification System) as a model drug. At a low concentration of Gly drug precipitation occurred while, for higher concentrations of Gly, a significant deterioration of mucoadhesive and mechanical properties was observed. One possible way to overcome all these problems could be the addition of hydroxypropyl-ß-cyclodextrin (HP-ß-CD) to the GG-Gly formulation as a drug-precipitation inhibitor. In this work the effect of cyclodextrin addition on the mechanical, mucoadhesive, swelling and release properties of GG-Gly films was investigated. In-vitro drug release studies were carried out using the paddle type dissolution apparatus (USP II) and the millifluidic flow-through device (MFTD). A moving-boundary model for swelling dynamics and release in USP II is proposed to estimate the effective diffusivity of the solvent, HP-ß-CD, fluconazole and complex fluconazole/HP-ß-CD in the swelling film. Experimental results, supported by theoretical modeling, confirmed that gellan gum-low glycerol thin films including HP-ß-CD represent a suitable formulation for fluconazole drug delivery. A sustained release was observed when GG-Gly film is loaded with a preformed complex fluconazole/HP-ß-CD.
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PEG-DMA was incorporated in unilamellar liposomes. PEG-DMA crosslinking by photo-induced radical reaction transforms the liquid aqueous core of the liposome into a hydrogel. The molecular weight of PEG-DMA significantly influences both structural and release properties of these hybrid nanosystems, by affecting both membrane permeability and diffusional properties of the inner core. Release studies of 5-(6) carboxyfluorescein from Conventional Liposomes (CL) and Gel-in-Liposome (GiL) systems were carried out in a vertical Franz Diffusion Cell. A detailed transport model is proposed, aimed at describing the entire drug diffusive pathway from the vesicles' inner core, through the double-layer membrane, into the buffer solution in the donor chamber of the Franz Cell and from there to the receptor chamber, where withdrawals are performed to evaluate the released drug concentration. The model permits to give a quantitative estimate of the diffusional resistances offered by the inner core (liquid or gelled) and by the double-layer membrane for CLs and different GiLs systems. The theoretical analysis of experimental release data strongly supports the basic assumption that, by varying the molecular weight of PEG-DMA, a different arrangement of the polymer within the liposomal structure and a different interaction with the membrane occur. PEG750-DMA decreases the transport resistance of the double layer membrane with respect to CLs, while PEG4000-DMA plays the opposite role. After gelation of the internal core, the diffusional resistance to drug transport inside GiLs becomes controlling, thus significantly slowing down drug release from these systems. Therefore, the combination of PEG-DMA with phospholipid vesicles appears an interesting strategy to develop sustained drug delivery systems.
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Química Farmacéutica/métodos , Sistemas de Liberación de Medicamentos/métodos , Fluoresceínas/farmacocinética , Metacrilatos/química , Polietilenglicoles/química , Liposomas Unilamelares/química , Línea Celular , Permeabilidad de la Membrana Celular , Supervivencia Celular , Colesterol/química , Liberación de Fármacos , Hidrogeles/química , Interacciones Hidrofóbicas e Hidrofílicas , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Peso Molecular , Fosfatidilcolinas/químicaRESUMEN
Since the application of nanotechnology to drug delivery, both polymer-based and lipid-based nanocarriers have demonstrated clinical benefits, improving both drug efficacy and safety. However, to further address the challenges of the drug delivery field, hybrid lipid-polymer nanocomposites have been designed to merge the beneficial features of both polymer-based and lipid-based delivery systems in a single nanocarrier. Within this scenario, this work is aimed at developing novel hybrid vesicles following the recent strategy of modifying the internal structure of liposomes. Specifically, polyethylene glycol-dimethacrylate (PEG-DMA, molecular weight 750 or 4000), was entrapped within unilamellar liposomes made of hydrogenated soybean phosphatidylcholine/cholesterol, and photo-crosslinked, in order to transform the aqueous inner core of liposomes into a soft and elastic hydrogel. After appropriate optimization of the preparation and gelation procedures, the primary objective of this work was to analyze the effect of the molecular weight of PEG-DMA on the main properties of these Gel-in-Liposome (GiL) systems. Indeed, by varying the molecular weight of PEG-DMA also its hydrophilic/lipophilic balance was modified and different arrangements of the polymer within the structure of liposomes as well as different interaction with their membrane were obtained. Both polymers were found in the inner core of the liposomes, however, the more hydrophobic PEG750-DMA also formed localized clusters within the liposome membrane, whereas the more hydrophilic PEG4000-DMA formed a polymeric corona on the vesicle surface. Preliminary cytotoxicity studies were also performed to evaluate the biological safety of these GiL systems and their suitability as innovative materials drug delivery application.