The thermosensitive behavior of microgel particles suspended in solvents, i.e. their temperature-dependent swelling properties, has triggered ongoing interest in industry and academia over the past forty years. The most-studied polymer is poly(N-isopropylacrylamide) - PNIPAM -, where the volume phase transition temperature is well known to depend on the detailed molecular architecture of the monomers. In this article, we focus on publications mostly of the past five years in chemical synthesis, aiming at shifting or controlling the volume phase transition temperature (VPTT) of such polymers by copolymerization of a main monomer - often from the PNIPAM family - with either monomers of different hydrophobicity, or with ones bearing ionizable groups. In some cases, hydrophobicity may be modulated by light as external switching parameter, whereas ionic strength or pH may act on the thermosensitivity of the microgels containing charged groups. Due to either differences in reactivity, or specific synthesis routes, particular microgel morphologies, such as molecular gradient, core-shell, interpenetrated, or patchy (multi-lobular) structures may be generated. They may give rise to spatial modulations of thermosensitivity within particles and are highlighted in this review. Our short overview shows that multiple external control of VPTT and morphology is commonly achieved nowadays.

We have synthesized novel acrylamide-based copolymer microgels exhibiting a volume phase transition temperature (VPTT) well-above the one of poly-N-isopropylacrylamide (pNIPAM). The high VPTT is achieved by copolymerization of three different main monomers N,N-propylacrylamide (NNPAM), NIPAM, and N-isopropylmethacrylamide (NIPMAM), with the hydrophilic comonomer NIPMAMol (N-(1-hydroxy-2-propyl)methacrylamide). Nuclear magnetic resonance spectroscopy (NMR) shows a high incorporation of NIPMAMol into the microgels, approaching 100 %. The swelling behavior of the microgels in solution has been studied by photon correlation spectroscopy and turbidity measurements, evidencing the increase in VPTT with NIPMAMol content. We determined an ideal VPTT of pNIPMAMol homopolymer microgels to be 85 degrees C by extrapolation, highlighting the strong impact of this comonomer on the swelling behavior of the microgels. Finally, the microgel shape in the dried state has been studied via scanning electron microscopy. For high NIPMAMol contents a second, large species is observed, exhibiting a core-shell structure. This sheds light on the polymerization mechanism in the presence of high VPTT comonomers.

Abstract Objective Hydroxyapatite (HAP; Ca5(PO4)3(OH)) is used in oral care formulations as a remineralizing agent and acts as a reservoir for calcium and phosphate ions. Consequently, HAP can serve as a neutralizing agent during acidic attacks caused by erosive beverages or cariogenic processes. This in vitro study aims to investigate the neutralization potential of HAP particles, used in oral care products, with a focus on changes in pH value, Ca2+ release, and structural integrity. Materials and methods 5.0% (w/v) particulate HAP was added to hydrochloric acid, phosphoric acid, citric acid, and lactic acid (37 °C, 0.1 M), as well as to Sprite® and Coca-Cola®, all under continuous stirring. pH values were measured after equilibration. Neutralization kinetics of HAP were investigated in Sprite® and Coca-Cola® within the first 30 s after addition of 0.15% (w/v), 0.5% (w/v), and 5.0% (w/v) HAP. Scanning electron microscopy (SEM) and X-ray powder diffraction (XRD) were employed to investigate crystallite morphology and composition. Atomic absorption spectroscopy (AAS) was conducted to analyze Ca2+ release. Results The investigated HAP shows a significant increase in pH in all systems and neutralizes between 98.0% and 99.9% of the acidic protons in the equilibrium. Up to 2619 mg L−1 ± 48 mg L−1 of Ca2+ are released in hydrochloric acid, while the porous particle structure remains unaffected. Kinetic investigation in beverages shows that already 0.15% (w/v) HAP neutralizes most of the dissociated acid within 20 s (83.9% in Sprite®, 98.7% in Coca-Cola®). Conclusions The study shows that HAP used in oral care formulations can efficiently counteract acids by increasing pH value and releasing Ca2+ ions, while retaining its functional morphology.

The effects of hard confinement are of great importance for many applications and also from a scientific point of view. These effects include a reduction in degrees of freedom and changes in phase behavior, structure, and molecular interactions. Simple and complex fluids can enter and occupy a porous matrix by imbibition. In this work, the results of an investigation into the spontaneous imbibition of bicontinuous microemulsions, serving as a model system for a complex fluid, into columns of granular, controlled pore glasses (CPG) are reported. The spontaneous imbibition of 1-octanol, a simple fluid with viscosity and surface tension similar to the bicontinuous microemulsion, is investigated for comparison. Controlled pore glasses with three different pore diameters between 11 and 112 nm with hydrophilic and hydrophobic surfaces are chosen. Two imbibition regimes were observed for the three investigated controlled porous glasses. Comparatively fast imbibition occurs due to the presence of voids between the individual CPG grains, while the uptake of liquids into the actual pores is much slower.

Hybrid hydrogel-nanocapsule systems are promising platforms for topical drug delivery; however, the impact of polymer structural modulation on nanocapsule organization and multiscale structure-property relationships remains insufficiently understood. Herein, galactomannan-poly(ε-caprolactone) (PCL) hybrid hydrogels containing α-bisabolol-loaded nanocapsules were prepared with different BTCA concentrations to investigate the effect of polymer chain modulation on nanocapsule organization and physicochemical properties. The resulting systems were characterized by a multiscale approach combining photon correlation spectroscopy (PCS), high-performance size exclusion chromatography (HPSEC), Fourier transform infrared spectroscopy (FTIR), cryogenic transmission electron microscopy (cryo-TEM), small- and wide-angle X-ray scattering (SAXS/WAXS), differential scanning calorimetry (DSC), and rheological analysis. α-Bisabolol-loaded poly(ε-caprolactone) nanocapsules (BNC) exhibited a hydrodynamic radius of 98 ± 1 nm. HPSEC demonstrated a concentration-dependent reduction in the weight-average molar mass of galactomannan from ~1.5 ∙ 106 g/mol, confirming chain modification, consistent with FTIR analysis. WAXS and DSC confirmed preservation of the semicrystalline PCL lamellar structure under hydrated conditions, whereas rheological analyses revealed reduced chain entanglement while maintaining shear-thinning behavior. These findings establish direct structure-property relationships, demonstrating the potential of BTCA-mediated galactomannan modulation to control nanocapsule organization and engineer hybrid hydrogels for topical drug delivery.

Biological lipid membranes can be mimicked by small unilamellar vesicles (SUVs), which e.g. consist of the negatively charged phospholipid 1,2-dioleoyl-sn-glycero-3-phosphatidylglycerol (DOPG). Due to the unsaturated hydrocarbon chains and hence the low main phase transition temperature, a DOPG membrane is always fluid-like in aqueous solution. By addition of cholesterol to the DOPG model membrane, the membrane stiffness is found to increase. These cholesterol-containing DOPG SUVs are characterized in the presence of varying amounts of the saponins aescin and glycyrrhizin at a temperature of 30°C by diffusion-ordered nuclear magnetic resonance spectroscopy (DOSY NMR), small-angle neutron scattering (SANS), small- and wide-angle X-ray scattering (SAXS, WAXS), neutron spin echo spectroscopy (NSE), and cryogenic transmission electron microscopy (cryo-TEM). All methods reveal that cholesterol is incorporated into the long-term stable SUVs. Upon saponin addition up to a molar ratio of 1:1 no significant modifications of the SUV size parameters are detected. However, NSE reveals a slight alteration in the membrane elasticity. In sum, the DOSY NMR and scattering results clearly show the coexistence of DOPG-cholesterol SUVs and saponin unimers or micelles and an interaction from the outside of the DOPG vesicles seems to promote the change in the membrane rigidity.

Marine triterpenoid saponins are structurally diverse metabolites with high pharmacological and nutraceutical potential, yet their characterization remains challenging due to extensive isomerism, aggregation phenomena, and the frequent co-extraction of lipids and other matrix components. In this work, we combine ATR–FTIR and high-resolution LC–MS to investigate the spectral and chromatographic behaviour of Cucumaria frondosa extracts and butanol-enriched fractions. FTIR spectra reveal a strong aliphatic signature, N–H-related features, and ester carbonyl bands consistent with the presence of co-extracted lipids and nitrogen-containing species such as ceramides or sphingolipids. LC–MS analysis of preparative fractions shows recurrent saponin-like ions— most prominently a feature at m/z≈1347—reappearing across chromatographically distinct fractions, often accompanied by lipid-like ions in the 600–900 m/z range. These observations indicate that closely associated lipidic species can modulate the apparent chromatographic behaviour of saponin-containing fractions.

The thermosensitivity and microstructure of microgels made by copolymerizing standard microgel-forming monomers with more hydrophilic comonomers are investigated, with the aim of increasing the volume phase transition temperature (VPTT). We precisely determine the incorporation of N-(hydroxymethyl)acrylamide (HMAM) and purpose-synthesized N-(2-hydroxyisopropyl)acrylamide (HIPAM) into microgels, neither of which forms microgels on its own by precipitation polymerization. The swelling properties and microstructure of the resulting copolymer microgels with N-isopropylacrylamide (NIPAM, LCST of ∼32 °C) and N-isopropylmethacrylamide (NIPMAM, LCST of ∼44 °C) are then characterized via turbidimetry, DLS, and AFM. At low comonomer contents, all microgel particles exhibit moderate growth. Beyond a system-specific threshold, we observe a significant increase in size and smoother swelling behavior. For NIPAM-HIPAM, the size increase is linked to a strong increase in swelling capacity and the formation of a thick corona. The effect of the hydrophilic comonomers on the VPTT correlates linearly with their true composition, allowing us to extrapolate the VPTT of hypothetical pure HMAM and HIPAM microgels. This leads to values of 99 °C for HMAM and 68 °C for HIPAM for the respective VPTT. These numbers can be seen as useful indicators of the effect of these monomers on the VPTT in the copolymerized microgels. The observed changes in VPTT, swelling, size, and morphology suggest that high-VPTT microgels possess unique internal molecular composition gradients, likely due to hydrophobic interactions during synthesis. Our results have potential implications for developing temperature-sensitive microgel-based membranes that can self-adapt their permeability at higher operating temperatures in energy applications.

The expanding field of nutraceuticals and functional food science is increasingly turning to marine-derived bioactive compounds, particularly saponins, for their diverse pharmacological properties. These so-called thalassochemicals display distinctive structural features—such as sulfated glycosidic moieties and amphiphilic backbones—that underpin potent antitumor, hypolipidemic, antioxidant, and antimicrobial activities. In contrast to their terrestrial analogs, marine saponins remain underexplored, and their complexity poses analytical and functional challenges. This review provides a critical and integrative synthesis of recent advances in the structural elucidation, biological function, and technological application of marine saponins. Special emphasis is placed on the unresolved limitations in their isolation, characterization, and structural validation, including coelution of isomers, adduct formation in MS spectra, and lack of orthogonal techniques such as NMR or FTIR. We illustrate these limitations through original MS/MS data and propose experimental workflows to improve compound purity and identification fidelity. In addition to discussing known structure–activity relationships (SARs) and mechanisms of action, we extend the scope by integrating recent developments in computational modeling, including machine learning, molecular descriptors, and quantitative structure–activity relationship (QSAR) models. These tools offer new avenues for predicting saponin bioactivity, despite current limitations in available high-quality datasets. Furthermore, we include a classification and comparison of steroidal and triterpenoid saponins from marine versus terrestrial sources, complemented by detailed chemical schematics. We also address the impact of processing techniques, delivery systems, and bioavailability enhancements using encapsulation and nanocarriers. Finally, this review contextualizes these findings within the regulatory and sustainability frameworks that shape the future of saponin commercialization. By bridging analytical chemistry, computational biology, and food technology, this work establishes a roadmap for the targeted development of marine saponins as next-generation nutraceuticals and functional food ingredients.

β-Aescin is a natural additive employed for treatments of vascular insufficiency, hence its impact in red blood cell (RBC) adaptivity has been conjectured. Here, we report a study about the mechanical impact of the membrane stiffener aescin on the flickering motions of live RBCs maintained at the homeostatic status. An active flickering, or nonequilibrium fluctuation dynamics has been revealed by mapping flickering motions in single RBCs treated or not with aescin. Experiments show that active RBC flickers adapt mechanically to β-escin, unlike the passive thermal fluctuations observed in lipid bilayers without an active skeleton. Mechanical connections for active flickering are theoretically argued to exist between an effective viscoelastic softness bestowed by the spectrin membrane cytoskeleton and the observed stiffness imposed by aescin as a rigidity modulator. From the unveiled diffusive mechanics, we model an adaptive RBC homeostasis that recapitulates the active flickering phenomenon as an optimal membrane softness upon a regulated friction as observed under aescin-induced membrane hardening. From a physiological perspective, RBC flicker adaptiveness to rigidization is discussed according to regulatory principles of energy conservation and minimal dissipation.

In this work, cationic core-shell microgels made from PNNPAM and two different amine monomers in core and shell are explored with respect to their interactions with the anionic drug naproxen. While the tertiary amine DAPMA is located inside the core to enable reversible capture of naproxen based on electrostatic interactions, the primary amine APMH in the shell opens the possibility for further conjugation of the microgels with other functionalities or biomolecules. The complementary use of different scattering, spectroscopic, and imaging techniques resolves the interaction of the microgels with the anionic drug naproxen. Despite having a cationic core, the interaction of naproxen and microgels is found to be mainly limited to the outer periphery of the microgels. With increasing pH, these interactions of electrostatic nature can be completely switched off. This enables the microgels to be used for the controlled uptake and release of naproxen, using pH as a trigger for the release.

We use small-angle neutron scattering (SANS) to investigate the structure and phase behavior of a complex fluid within meso- and macroporous matrices.

We analyze the swelling behavior of N-isopropylacrylamide (NIPAM)-based microgels incorporating the non-thermoresponsive comonomer N-tert-butylacrylamide (NtBAM) using photon correlation spectroscopy (PCS) and atomic force microscopy (AFM). Previous thermodynamic analysis of PNIPAM-co-NtBAM microgel swelling relied on the classical Flory-Rehner theory. However, this approach struggled to accurately describe swelling curves at higher NtBAM content. Our present work combines the original expression for the Flory-Huggins interaction parameter $$\chi _{FH}$$ χ FH for NtBAM with a recently adapted Hill-like model for the interaction parameter $$\chi _{Hill}$$ χ Hill that accounts for cooperative effects in the volume phase transition in poly(NIPAM) microgels. This approach outperforms other methods in fitting quality. The observed results are revealing an exponential decrease in hydrodynamic radius upon increasing NtBAM content for swollen microgels. In addition, an exponential decay of the number of water molecules leaving the polymer chain during the volume phase transition is found, which can be attributed to the steric influence of one NtBAM monomer on the hydration of neighboring NIPAM monomers. The molar interaction enthalpy $$\Delta H_{SP}= \text {-49 kJ / mol}$$ Δ H SP = -49 kJ / mol and entropy $$\Delta S_{SP} = \text {-177 J /( mol K)}$$ Δ S SP = -177 J /( mol K) were obtained from the fits of the swelling curves. Graphical Abstract

In the present work, the temperature-dependent phase behavior of a C10E4 based microemulsion is studied in different meso-macroporous glasses, as a function of their pore diameter. The phase behavior in these pores is investigated by small-angle X-ray scattering (SAXS). The crucial parameter we discuss based on the SAXS results is the domain size of the bicontinuous phase. Using a simplified model to fit the scattering data, we can observe the microemulsion inside the pores. These experiments reveal a temperature-dependent change in domain sizes of the bicontinuous microemulsion only for large pores. Possible temperature-dependent structure of the microemulsion within the pores of controlled pore glasses. Small pore sizes seem to affect the temperature-dependent phase behavior of the microemulsion.

Thermoresponsive microgels experience a volume phase transition triggered by temperature changes, a phenomenon often analyzed using dynamic light scattering to observe overall size alterations via the diffusion coefficient. However, local structural changes are typically assessed using more intricate and expensive techniques like small-angle neutron or X-ray scattering. In our research, we investigate the volume phase transition of poly-N-isopropylacrylamide (PNIPAM)-based microgels by employing a combination of temperature-dependent dynamic light scattering and simpler, faster, and more efficient attenuation measurements. We utilize attenuation at a fixed wavelength as a direct measure of dispersion turbidity, linking the absolute changes in hydrodynamic radius to the absolute changes in turbidity. This approach allows us to compare "classical" PNIPAM microgels from precipitation polymerization, charged copolymer microgels from precipitation copolymerization, and core-shell microgels from seeded precipitation polymerization. Our study includes a systematic analysis and comparison of 30 different microgels. By directly comparing data from dynamic light scattering and attenuation spectroscopy, we gain insights into structural heterogeneity and deviations from the established fuzzy sphere morphology. Furthermore, we demonstrate how turbidity data can be converted to swelling curves.

The properties of pH-responsive microgels are strongly influenced by the pH value during synthesis. In this work, based on a N-n-propylacrylamide (NNPAM) core with N-3-(dimethylamino)propylmethacrylamide (DAPMA) as a comonomer, a series of core-shell microgels with shells from NNPAM and N-(3-aminopropyl)methacrylamide hydrochloride (APMH) are synthesized at different pH values. While the swelling behavior is studied with temperature- and angle-dependent photon correlation spectroscopy (PCS), the size and morphology are also investigated by means of atomic force microscopy (AFM) and static light scattering (SLS). At acidic pH, rather monodisperse microgels with a very fuzzy shell are obtained. The microgels evolve particulate structures on their shell at intermediate pH until not only a core-shell microgel but also a secondary microgel species is produced at basic pH. By altering the synthesis pH, it is possible to influence the morphology of core-shell microgels to suit future applications like the uptake and release of drugs or surface modification.

Disc-like lipid nanoparticles stabilized by saponin biosurfactants display fascinating properties, including their temperature-driven re-organization. β-Aescin, a saponin from seed extract of the horse chestnut tree, shows strong interactions with lipid membranes and has gained interest due to its beneficial therapeutic implications as well as its ability to decompose continuous lipid membranes into size-tuneable discoidal nanoparticles. Here, we characterize lipid nanoparticles formed by aescin and the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine. We present site-resolved insights into central molecular interactions and their modulations by temperature and aescin content. Using the membrane protein bacteriorhodopsin, we additionally demonstrate that, under defined conditions, aescin-lipid discs can accommodate medium-sized transmembrane proteins. Our data reveal the general capability of this fascinating system to generate size-tuneable aescin-lipid-protein particles, opening the road for further applications in biochemical, biophysical and structural studies.

A set of poly(N-isopropylacrylamide) p(NIPAM) microgels was successfully prepared through precipitation polymerization (PP) using acryloyl starch nanoparticles (ASNPs) as crosslinkers. Functionalized starch nanoparticles used in microgel preparation, with a degree of substitution (DS) of 0.78 (ASNP12) or 1.37 (ASNP24) were found to have different properties. Dynamic light scattering (DLS) revealed that microgels prepared with ASNP12 exhibit a higher swelling capacity compared to the microgels designed with ASNP24, which was also observed by atomic force microscopy (AFM), showing super soft microgels flattened into disk shape on the substrate. This may be related to softer and surface smoothed microgels. Turbidity analysis revealed a slight shift of the so-called volume phase transition temperature (VPTT) towards higher values for microgels synthesized with ASNP24, indicating its contribution as a hydrophilic comonomer. Considering their high swelling capacity, these bio-based crosslinked microgels are potential materials for adsorptive processes. They can also be considered as candidates for biomedical applications due to the presence of a biopolymer in their structure.

The formation and properties of smart (stimuli-responsive) membranes are reviewed, with a special focus on temperature and pH triggering of gating to water, ions, polymers, nanoparticles, or other molecules of interest. The review is organized in two parts, starting with all-smart membranes based on intrinsically smart materials, in particular of the poly(N-isopropylacrylamide) family and similar polymers. The key steps of membrane fabrication are discussed, namely the deposition into thin films, functionalization of pores, and the secondary crosslinking of pre-existing microgel particles into membranes. The latter may be free-standing and do not necessitate the presence of a porous support layer. The temperature-dependent swelling properties of polymers provide a means of controlling the size of pores, and thus size-sensitive gating. Throughout the review, we highlight "positive" (gates open) or "negative" (closed) gating effects with respect to increasing temperature. In the second part, the functionalization of porous organic or inorganic membranes of various origins by either microgel particles or linear polymer brushes is discussed. In this case, the key steps are the adsorption or grafting mechanisms. Finally, whenever provided by the authors, the suitability of smart gating membranes for specific applications is highlighted.

Microplastic pollution and the urgent need for sustainable agriculture have raised interest in developing degradable carriers for controlled agrochemical release. Porous polymeric particles are particularly promising due to their unique release profiles compared to solid or core-shell carriers. However, creating degradable, mesoporous (2-50 nm) microparticles is challenging, and their potential for agrochemical delivery is largely unexplored. A straightforward self-assembly method is demonstrated for fully degradable porous polymer cubosomes (PCs), showcasing their ability to load and release agrochemicals. Using fully degradable block copolymers (BCPs), poly(ethyl ethylene phosphate)-b-polylactide (PEEP-b-PLA), PCs are synthesized in water with high inner order and open pores averaging 19 ± 3 nm in diameter. During the self-assembly process in the presence of the hydrophobic fungicide tebuconazole, polymersomes transform into PCs by enriching the hydrophobic polymer domain and altering the BCP packing parameter. After self-assemby, highly porous and fungicide-loaded PCs are obtained. Fungicide-loaded PCs show high antimycotic activity against Botrytis cinerea (grey mold), adhere to Vitis vinifera Riesling leaves even after simulated rain, and release the fungicide continuously over several days with different release-kinetics compared to solid particles. PCs hydrolyze completely into lactic acid and phosphate derivatives, highlighting their potential as microplastic-free agrochemical delivery systems for sustainable agriculture.