Aerogels are the lightest processed solid materials on Earth and with the largest empty volume fraction in their structure. Composition versatility, modularity, and feasibility of industrial scale ...manufacturing are behind the fast emergence of aerogels in the drug delivery field. Compared to other 3D materials, the high porosity (interconnected mesopores) and high specific surface area of aerogels may allow faster loading of small-molecule drugs, less constrained access to inner regions of the matrix, and more efficient interactions of the biological milieu with the polymer matrix. Processing in supercritical CO2 medium for both aerogel production (drying) and drug loading (impregnation) has remarkable advantages such as absence of an oxidizing environment, clean manufacture, and easiness for the scale-up under good manufacturing practices. The aerogel solid skeleton dictates the chemical affinity to the different drugs, which in turn determines the loading efficiency and the release pattern. Aerogels can be used to increase the solubility of BCS Class II and IV drugs because the drug can be deposited in amorphous state onto the large surface area of the skeleton, which facilitates a rapid contact with the body fluids, dissolution, and release. Conversely, tuning the aerogel structure by functionalization with drug-binding moieties or stimuli-responsive components, application of coatings and incorporation of drug-loaded aerogels into other matrices may enable site-specific, stimuli-responsive, or prolonged drug release. The present review deals with last decade advances in aerogels for drug delivery. An special focus is paid first on the loading efficiency of active ingredients and release kinetics under biorelevant conditions. Subsequent sections deal with aerogels intended to address specific therapeutic demands. In addition to oral delivery, the physical properties of the aerogels appear to be very advantageous for mucosal administration routes, such as pulmonary, nasal, or transdermal. A specific section devoted to recent achievements in gene therapy and theranostics is also included. In the last section, scale up strategies and life cycle assessment are comprehensively addressed.
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•Drug solubility in scCO2 and drug-skeleton interactions determine the amount loaded and the drug physical state•Release rate depends on drug crystalline state, drug-skeleton interactions and aerogel hydrophilicity and swelling•Aerogels are suitable for fast, sustained and stimuli-responsive oral drug delivery•The high porosity and specific surface make aerogels appealing for pulmonary, nasal, or transdermal•Gene therapy and theranostics can be accomplished with aerogels
The most relevant properties of polysaccharide aerogels in practical applications are determined by their microstructures. Hydration has a dominant role in altering the microstructures of these ...hydrophilic porous materials. To understand the hydration induced structural changes of monolithic Ca-alginate aerogel, produced by drying fully cross-linked gels with supercritical CO2, the aerogel was gradually hydrated and characterized at different states of hydration by small-angle neutron scattering (SANS), liquid-state nuclear magnetic resonance (NMR) spectroscopy, and magic angle spinning (MAS) NMR spectroscopy. First, the incorporation of structural water and the formation of an extensive hydration sphere mobilize the Ca-alginate macromolecules and induce the rearrangement of the dry-state tertiary and quaternary structures. The primary fibrils of the original aerogel backbone form hydrated fibers and fascicles, resulting in the significant increase of pore size, the smoothing of the nanostructured surface, and the increase of the fractal dimension of the matrix. Because of the formation of these new superstructures in the hydrated backbone, the stiffness and the compressive strength of the aerogel significantly increase compared to its dry-state properties. Further elevation of the water content of the aerogel results in a critical hydration state. The Ca-alginate fibers of the backbone disintegrate into well-hydrated chains, which eventually form a quasi-homogeneous hydrogel-like network. Consequently, the porous structure collapses and the well-defined solid backbone ceases to exist. Even in this hydrogel-like state, the macroscopic integrity of the Ca-alginate monolith is intact. The postulated mechanism accounts for the modification of the macroscopic properties of Ca-alginate aerogel in relation to both humid and aqueous environments.
Supercritically dried, mesoporous silica–gelatin hybrid aerogels of 4–24 wt % gelatin content show high selectivity for the adsorption of aqueous Hg(II) in the simultaneous presence of Cu(II), ...Cd(II), Co(II), Pb(II), Ni(II), Ag(I), and Zn(II), as demonstrated by batch adsorption experiments with multiple competing ions. The aerogels are characterized by SEM and N2 porosimetry, and their aqueous particle size distributions and zeta potentials are reported. The adsorption properties of the hybrid aerogels are studied as a function of their composition, initial aqueous Hg(II) concentration, contact time, and pH. The optimum pH for adsorption is 6.0, where the surface of the aerogel is already negatively charged, but Hg(II) does not completely hydrolyze. The Hg(II) uptake of the hybrid aerogels increases with increasing gelatin content and levels off at 24 wt % gelatin. The adsorption capacity of the 24 wt % gelatin hybrid is estimated to be S = 209 mg g–1 by fitting the isotherm with the Langmuir model (K L = 0.032 L mg–1). This translates to 91% Hg(II) removal at c 0(Hg) = 1.0 mg L–1 and c 0(aerogel) = 0.32 g L–1. Gelatin provides the active sites for Hg(II) binding; thus, higher gelatin content results in higher adsorption capacity. However, high gelatin content also induces the extensive swelling of backbone and the partial collapse of the open porous structure, which decreases the specific surface area. Time-resolved experiments show that the adsorption equilibrium is established within 15 min contact time with aqueous Hg(II). Washing the equilibrated aerogels with a 2.5 mM solution of EDTA complexing agent quantitatively liberates bound Hg(II). The regenerated aerogels demonstrate practically intact adsorption capacities in five cycles of reuse. Coordination chemistry based considerations reveal that Hg(II) is selectively complexed by the soft Lewis-base side chains of collagen.
The gelation of biopolymers is of great interest in the material science community and has gained increasing relevance in the past few decades, especially in the context of aerogelslightweight open ...nanoporous materials. Understanding the underlying gel structure and influence of process parameters is of great importance to predict material properties such as mechanical strength. In order to improve understanding of the gelation mechanism in aqueous solution, this work presents a novel approach based on the discrete element method for the mesoscale for modeling gelation of hydrogels, similarly to an extremely coarse-grained molecular dynamics (MD) approach. For this, polymer chains are abstracted as dimer units connected by flexible bonds and interactions between units and with the environment, that is, diffusion in implicit water, are described. The model is based on Langevin dynamics and includes an implicit probabilistic ion model to capture the effects of ion availability during ion-mediated gelation. The model components are fully derived and parameterized using literature data and theoretical considerations based on a simplified representation of atomistic processes. The presented model enables investigations of the higher-scale network formation during gelation on the micrometer and millisecond scale, which are beyond classical modeling approaches such as MD. As a model system, calcium-mediated alginate gelation is investigated including the influence of ion concentration, polymer composition, polymer concentration, and molecular weight. The model is verified against numerous literature data as well as own experimental results for the corresponding Ca-alginate hydrogels using nitrogen porosimetry, NMR cryoporometry, and small-angle neutron scattering. The model reproduces both bundle size and pore size distribution in a reasonable agreement with the experiments. Overall, the modeling approach paves the way to physically motivated design of alginate gels.
Mesoporous silica aerogels have a wide range of potential applications in biotechnology, the food industry, pharmacy and medicine. Understanding the nature of the interactions of biomolecules with ...these porous nanostructured materials is essential for achieving optimum performance in the targeted applications. In this study, the well-characterized bovine serum albumin (BSA) was chosen as a model protein to probe protein-aerogel interactions in the solution phase. Aqueous BSA was mixed with suspended silica aerogel microparticles, and the colloid system was monitored on-line by UV-vis spectrophotometry and turbidimetry. The global mathematical analysis of the time-resolved data reveals that the fast sorption of the protein on the aerogel microparticles follows a multistep binding mechanism. The extensive sorption of the protein eventually induces the aggregation of the covered aerogel due to the alteration of the electrical double layer of the particles. The interaction of BSA and silica aerogel is the strongest between pH = 4 and 5, because their native surface charges are the opposite in this pH range, as indicated by their respective zeta potentials.
Silica-gelatin hybrid aerogel of 24 wt% gelatin content is an advanced functional material suitable for the high performance selective adsorption of aqueous Hg(II). The remediation efficacy of this ...adsorbent was tested under realistic aquatic conditions by exposing cultures of Paramecium caudatum to Hg(II) and monitoring the model cultures by time-lapse video microscopy. The viability of Paramecium was quantified by analyzing the pixel differences of the sequential images caused by the persistent movement (motility) of the cells. The viability of Paramecium displays a clear exposure-response relationship with Hg(II) concentration. Viability decreases with increasing Hg(II) concentration when the latter is higher than 125 μg L−1. In the presence of 0.1 mg mL−1 aerogel adsorbent, the viability of the cells decreases only at Hg(II) concentrations higher than 500 μg L−1, and 220 min survival time was measured even at 1000 μg L−1 Hg(II). The effective toxicity of Hg(II) is lower in the presence of the aerogel, because the equilibrium concentration of aqueous Hg(II) is low due to adsorption, thus Paramecium cells do not uptake as much Hg(II) as in the un-remediated cultures. Video imaging of Paramecium cultures offers a simple, robust and flexible method for providing quantitative information on the effectiveness of advanced materials used in adsorption processes for water treatment.
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•Paramecium caudatum used as bioindicator of Hg(II) toxicity.•Paramecium cultures monitored by time lapse video microscopy imaging.•Quantitative exposure-effect relationship established for Hg(II) toxicity.•Silica-gelatin aerogel effectively protects Paramecium from Hg(II).
The imaging of non-conducting materials by scanning electron microscopy (SEM) is most often performed after depositing few nanometers thick conductive layers on the samples. It is shown in this work, ...that even a 5 nm thick sputtered gold layer can dramatically alter the morphology and the surface structure of many different types of aerogels. Silica, polyimide, polyamide, calcium-alginate and cellulose aerogels were imaged in their pristine forms and after gold sputtering utilizing low voltage scanning electron microscopy (LVSEM) in order to reduce charging effects. The morphological features seen in the SEM images of the pristine samples are in excellent agreement with the structural parameters of the aerogels measured by nitrogen adsorption-desorption porosimetry. In contrast, the morphologies of the sputter coated samples are significantly distorted and feature nanostructured gold. These findings point out that extra care should be taken in order to ensure that gold sputtering does not cause morphological artifacts. Otherwise, the application of low voltage scanning electron microscopy even yields high resolution images of pristine non-conducting aerogels.
A simple kinetic model is derived to describe the formation of TiO2 particles up to the size of a few hundred nanometers in an aqueous suspension. The model system for the kinetic experiments is the ...hydrolysis and condensation of titanium(IV)-bis(ammonium-lactato)dihydroxide under basic conditions. The formation of nanoparticles was followed by dynamic light scattering (DLS) and UV–vis spectrometric methods. The turbidity (i.e., the apparent absorbance at 500 nm) of a stable TiO2 suspension is shown to be proportional to the TiO2 concentration at a constant particle size and proportional to the size at a constant Ti concentration. The compilation of the DLS and UV–vis data yields characteristic sigmoid-shaped kinetic curves for the evolution of particle size. A kinetic model with three reaction steps is postulated which provides an excellent fit to the experimental data. First, the rapid hydrolysis of the precursor takes place to give primary particles for the subsequent steps. The dimerization of two primary particles is slow and this is followed by the formation of larger particles in the step-by-step addition of subsequent primary units. An integrated rate equation was developed to predict the time-dependent mean particle size as the function of the initial precursor concentration. An important feature of the model is that a simple continuous function describes the temporal evolution of the average particle size up to d = 600 nm. Previously published kinetic data representing various reaction systems were also successfully interpreted by the proposed model.
In the present work, tannin-modified whey protein isolate (WPI/tannin) aerogels were synthesized, and their hydration properties were evaluated. The materials were prepared by introducing two ...different tannins (one hydrolyzable and one condensed) in the protein matrix via thermal-induced gelation of neutral or alkaline aqueous solutions (pH 7, 9, or 11) at 80 °C. WPI and WPI/tannin aerogels are nanostructured porous materials with high BET surface areas (216–353 m2 g–1). Subsequently, WPI and WPI/tannin aerogels were hydrophobized via silanization (with bis(trimethylsilyl)amine) in the gas phase (HWPI and HWPI/tannin aerogels). As a result of silanization, BET surface areas were reduced to 87–242 m2 g–1. The hydration properties of all aerogels were studied by measuring the water uptake and water contact angles. Pristine WPI aerogels absorbed high amounts of water (up to 4794% w/w in 24 h), swelled, and eventually disintegrated. WPI/tannin aerogels prepared with the condensed tannin absorbed more water (219–559% w/w) than those prepared with the hydrolyzable tannin (81–88% w/w). In any case, the water uptake was significantly lower compared with that of pristine WPI aerogels. After silanization, all aerogels absorbed much smaller amounts of water (39–84% w/w). The reduced water uptake was in agreement with the water contact angles, which were in the ranges 35–55° for WPI aerogels, 40–60° for WPI/tannin aerogels, 80–86° for HWPI aerogels, and 100–116° for HWPI/tannin aerogels. These results clearly indicate that both the introduction of tannin in the protein matrix and the silanization of the solid network are necessary to obtain water-stable WPI-based aerogels. There is an immense need for replacing the existing plastic-based food packaging with biobased and biodegradable materials. In this context, our results address the major disadvantage of most biobased materials (i.e., poor stability in aqueous environments) and render these new aerogels good candidates for food packaging applications.
•Synthesis of spherical (d = 3–5 mm) Fe(III)-alginate aerogel particles.•Detailed characterization of Fe(III)-alginate aerogel (including SAXS).•Impregnation of aerogel spheres with ibuprofen and ...ascorbic acid in sc. CO2.•Incorporated ascorbic acid markedly increases the rate of drug release.
Iron(III)-crosslinked alginate aerogel beads (d = 3–5 mm) were prepared and loaded with ibuprofen by using the technique of adsorptive deposition from supercritical CO2. Additional formulations were prepared where the aerogels were co-impregnated by ibuprofen and ascorbic acid. The release of ibuprofen from the Fe(III)-alginate is much faster in pH = 7.4 (PBS) than in pH = 2.0 (HCl), which can be explained by the faster dissolution and higher swelling of the alginate matrix in PBS. By decreasing the size of the beads and using a higher G content alginate the release rate could be slightly increased. A marked acceleration of drug release was achieved in both HCl and PBS by incorporating ascorbic acid into the Fe(III)-alginate aerogel preparations. The explanation is that in aqueous media ascorbic acid in situ reduces the crosslinking Fe(III) to Fe(II). The latter does not interact strongly with alginate, which promotes the hydration of the chains, thus the erosion and dissolution of the carrier matrix.
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