Search Results (25)

Microgels, combining the properties of hydrogels and microparticles, are emerging as versatile materials for varied applications such as drug delivery and sensing, although the precise control of particle size remains a challenge. Advances in synthetic methodologies have provided new tools for tailoring of properties, however costs and scalability of the processes remains a limitation. We report here the water-based synthesis of a library of N-isopropylacrylamide-based microgels covalently crosslinked with varying contents of N,N′-methylenebisacrylamide. The results highlight the versatility of water as a synthetic medium, which yields large and monodisperse microgels, with excellent control over size. Dynamic light scattering data demonstrate that by increasing the total monomer concentration from 1 to 3 wt%, the particle size is increased by up to 4.9-fold. Crosslinker content allows fine-tuning of microgel size, with greater relevance for functionalised microgels. Functional co-monomers such as N-(3-aminopropyl)methacrylamide hydrochloride and N-(hydroxymethyl)acrylamide are shown to influence size and thermoresponsive behaviour, with hydrogen-bonding monomers reducing particle size and increasing the volume phase transition temperature by 2 °C. Positively charged monomers show a size reduction upon heating but provide colloidal stability at temperatures up to 60 °C. These findings emphasize the importance of tailoring synthetic conditions and formulations to optimize microgel properties for specific applications. Full article

This study aims to design microgels that are thermo- and pH-sensitive for controlled doxorubicin (Dox) release in response to tumor microenvironment changes. N-isopropylacrylamide (NIPAAm) is widely used for thermoresponsive tumor-targeted drug delivery systems for the release of therapeutic payloads in response to temperature changes. Herein, a NIPAAm microgel (MP) that is responsive to temperature and pH was designed for the smart delivery of Dox. MP was made from NIPAAm, and polyethylene glycol methyl ether methacrylate (PEGMA) was copolymerized with 5%, 10%, or 15% mol of methacryloylamido hexanoic acid, (CAM5) an amphiphilic acid. We characterized the microgels using FTIR-ATR, DLS, and FESEM. The MP 10% CAM5 exhibited a particle size of 268 nm, with a transition temperature of 44 °C. MP had a drug loading capacity of 13% and entrapment efficiency of 87%. Nearly 100% of the Dox was released at pH 5 and 42 °C, compared to 30% at pH 7.4 and 37 °C. MP 10% CAM5 showed cytocompatibility in HeLa cells using the MTT assay. However, the cell viability assay showed that dox-MP was twice as effective as free Dox. Specifically, 3 μg/mL of free Dox resulted in 74% cell viability, while the same doses of Dox in NP reduced it to 35%. These results are promising for the future tumor-targeted delivery of antineoplastic-drugs, as they may reduce the side effects of Dox. Full article

Stimuli-responsive microgels have attracted great interest in recent years as building blocks for fabricating smart surfaces with many technological applications. In particular, PNIPAM microgels are promising candidates for creating thermo-responsive scaffolds to control cell growth and detachment via temperature stimuli. In this framework, understanding the influence of the solid substrate is critical for tailoring microgel coatings to specific applications. The surface modification of the substrate is a winning strategy used to manage microgel–substrate interactions. To control the spreading of microgel particles on a solid surface, glass substrates are coated with a PEI or an APTES layer to improve surface hydrophobicity and add positive charges on the interface. A systematic investigation of PNIPAM microgels spin-coated through a double-step deposition protocol on pristine glass and on functionalised glasses was performed by combining wettability measurements and Atomic Force Microscopy. The greater flattening of microgel particles on less hydrophilic substrates can be explained as a consequence of the reduced shielding of the water–substrate interactions that favors electrostatic interactions between microgels and the substrate. This approach allows the yielding of effective control on microgel coatings that will help to unlock new possibilities for their application in biomedical devices, sensors, or responsive surfaces. Full article

Combinations of synthetic polymers, such as poly(N-isopropylacrylamide) (PNIPAM), with natural biomolecules, such as keratin, show potential in the field of biomedicine, since these hybrids merge the thermoresponsive properties of PNIPAM with the bioactive characteristics of keratin. This synergy aims to produce hybrids that can respond to environmental stimuli while maintaining biocompatibility and functionality, making them suitable for various medical and biotechnological uses. In this study, we exploit keratin derived from wool waste in the textile industry, extracted via sulfitolysis, to synthesize hybrids with PNIPAM microgel. Utilizing two distinct methods—polymerization of NIPAM with keratin (HYB-P) and mixing preformed PNIPAM microgels with keratin (HYB-M)—resulted in hybrids with 20% and 25% keratin content, respectively. Dynamic light scattering (DLS) and transmission electron microscopic (TEM) analyses indicated the formation of colloidal systems with particle sizes of around 110 nm for HYB-P and 518 nm for HYB-M. The presence of keratin in both systems, 20% and 25%, respectively, was confirmed by spectroscopic (FTIR and NMR) and elemental analyses. Distinct structural differences were observed between HYB-P and HYB-M, suggesting a graft copolymer configuration for the former hybrid and a complexation for the latter one. Furthermore, these hybrids demonstrated temperature responsiveness akin to PNIPAM microgels and pH responsiveness, underscoring their potential for diverse biomedical applications. Full article

In nature, some creatures can change their body shapes and surface colors simultaneously to respond to the external environments, which greatly inspired researchers in the development of color-tunable soft actuators. In this work, we present a facile method to prepare a smart hydrogel actuator that can bend bidirectionally and change color simultaneously, just like an octopus. The actuator is fabricated by elastomer/hydrogel bilayer and the hydrogel layer was decorated with thermoresponsive microgels as the photonic crystal blocks. Compared with the previously reported poly(N-isopropylacrylamide) hydrogel-based bilayer hydrogel actuators, which are generally limited to one-directional deformation, the elastomer/hydrogel bilayer actuator prepared in our work exhibits unique bidirectional bending behavior in accordance with the change of structural color. The bending degrees can be changed from −360° to 270° in response to solution temperatures ranging from 20 °C to 60 °C. At the same time, the surface color changes from red to green, and then to blue, covering the full visible light spectrum. The bending direction and degree of the hydrogel actuator can easily be adjusted by tuning the layer thickness ratio of the elastomer/hydrogel or the composition of the hydrogel. The color-tunable hydrogel-elastomer actuator reported in this work can achieve both programmable deformations and color-changing highly resembling the natural actuating behaviors of creatures. Full article

The synthesis of titania-based composite materials with anticancer potential under visible-light irradiation is the aim of this study. In specific, titanium dioxide (TiO₂) nanoparticles (NPs) chemically modified with silver were embedded in a stimuli-responsive microgel (a crosslinked interpenetrating network (IP) network that was synthesized by poly (N-Isopropylacrylamide) and linear chains of polyacrylic acid sodium salt, forming composite particles. The ultimate goal of this research, and for our future plans, is to develop a drug-delivery system that uses optical fibers that could efficiently photoactivate NPs, targeting cancer cells. The produced Ag-TiO₂ NPs, the microgel and the composite materials were characterized through X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), micro-Raman spectroscopy, ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering (DLS) and transmission electron microscopy (TEM). Our results indicated that Ag-TiO₂ NPs were successfully embedded within the thermoresponsive microgel. Either Ag-TiO₂ NPs or the composite materials exhibited high photocatalytic degradation efficiency on the pollutant rhodamine B and significant anticancer potential under visible-light irradiation. Full article

This study aimed to develop and evaluate thermoresponsive in situ microgels for the local ocular delivery of prednisolone (PRD) (PRD microgels) to improve drug bioavailability and prolong ocular drug residence time. Lipid nanosystems of PRD microemulsions (PRD-MEs) were prepared and evaluated at a drug concentration of 0.25–0.75%. PRD microgels were prepared by incorporating PRD-MEs into 10 and 12% Pluronic^® F127 (F127) or combinations of 12% F127 and 1–10% Kolliphor^®P188 (F68). PRD microgels were characterized for physicochemical, rheological, and mucoadhesive properties, eye irritation, and stability. Results showed that PRD-MEs were clear, miscible, thermodynamically stable, and spherical with droplet size (16.4 ± 2.2 nm), polydispersity index (0.24 ± 0.01), and zeta potential (−21.03 ± 1.24 mV). The PRD microgels were clear with pH (5.37–5.81), surface tension (30.96–38.90 mN/m), size, and zeta potential of mixed polymeric micelles (20.1–23.9 nm and −1.34 to −10.25 mV, respectively), phase transition temperature (25.3–36 °C), and gelation time (1.44–2.47 min). The FTIR spectra revealed chemical compatibility between PRD and microgel components. PRD microgels showed pseudoplastic flow, viscoelastic and mucoadhesive properties, absence of eye irritation, and drug content (99.3 to 106.3%) with a sustained drug release for 16–24 h. Microgels were physicochemically and rheologically stable for three to six months. Therefore, PRD microgels possess potential vehicles for local ocular delivery. Full article

The phase transition behavior of differently crosslinked poly(N-isopropylacrylamide)/N,N’-methylenebisacrylamide (PNiPAM/BIS) microgels with varying crosslinker content is investigated in presence of aromatic additives. The influence of meta-hydroxybenzaldehyde (m-HBA) and 2,4-dihydroxybenzaldehyde (2,4-DHBA), chosen as model drugs, on the volume phase transition temperature (VPTT) is analyzed by dynamic light scattering (DLS), differential scanning calorimetry (DSC), and ¹H-NMR, monitoring and comparing the structural, calorimetric, and dynamic phase transition, respectively. Generally, the VPTT is found to increase with crosslinker content, accompanied by a drastic decrease of transition enthalpy. The presence of an additive generally decreases the VPTT, but with distinct differences concerning the crosslinker content. While the structural transition is most affected at lowest crosslinker content, the calorimetric and dynamic transitions are most affected for an intermediate crosslinker content. Additive uptake of the collapsed gel is largest for low crosslinked microgels and in case of large additive-induced temperature shifts. Furthermore, as temperature is successively raised, ¹H NMR data, aided by spin relaxation rates, reveal an interesting uptake behavior, as the microgels act in a sponge-like fashion including a large initial uptake and a squeeze-out phase above VPTT. Full article

Thermo-responsive (TR) gels of the LCST (lower critical solution temperature) type swell in water at temperatures below their volume phase transition temperature $T_{\mathrm{c}}$ and collapse above the critical temperature. When water is partially replaced with an organic liquid, these materials demonstrate three different types of equilibrium solvent uptake diagrams at temperatures below, above, in the close vicinity of $T_{\mathrm{c}}$. A model is developed for equilibrium swelling of TR gels in binary mixtures of solvents. It takes into account three types of phase transitions in TR gels driven by (i) aggregation of hydrophobic side groups into clusters from which solvent molecules are expelled, (ii) replacement of water with cosolvent molecules in cage-like structures surrounding these groups, and (iii) replacement of water with cosolvent as the main element of hydration shells around backbone chains. The model involves a relatively small number of material constants that are found by matching observations on covalently cross-linked poly(N-isopropylacrylamide) macroscopic gels and microgels. Good agreement is demonstrated between the experimental data and results of numerical analysis. Classification is provided of the phase transition points on equilibrium swelling diagrams. Full article

In the present article, we use an improved Flory–Rehner theory to describe the swelling behavior of copolymer microgels, where the interaction parameter is modeled by a Hill-like equation for a cooperative thermotropic transition. This description leads to very good fits of the swelling curves of the copolymer microgels at different comonomer contents (30 mol%, 50 mol% and 70 mol%) obtained by photon correlation spectroscopy. Fixed parameters, which are universally applicable for the respective monomers given in our previous work, are used to fit the swelling curves. The analysis of the swelling curves yields physically reasonable and meaningful results for the remaining adjustable parameters. The comonomer content of the statistical copolymer microgels poly(NNPAM-co-NIPAM), poly(NIPAM-co-NIPMAM) and poly(NIPMAM-co-NNPAM) is determined by nuclear magnetic resonance spectroscopy and is in agreement with the nominal comonomer feed used in the synthesis. To investigate the volume phase transition at a molecular level, swelling curves are also measured by Fourier transformation infrared spectroscopy. The obtained swelling curves are also fitted using the Hill-like model. The fits provide physically reasonable parameters too, consistent with the results from photon correlation spectroscopy. Full article

Micro- and nanogels are being increasingly used to encapsulate bioactive compounds. Their soft structure allows large loading capacity while their stimuli responsiveness makes them extremely versatile. In this work, the complexation of DNA with thermoresponsive microgels is presented. To this end, PEGylated charged microgels based on poly-N-isopropylacrylamide have been synthesized, allowing one to explore the electrostatics of the complexation. Cationic microgels complexate spontaneously by electrostatic attraction to oppositely charged DNA as demonstrated by electrophoretic mobility of the complexes. Then, Langmuir monolayers reveal an increased interaction of DNA with swollen microgels (20 °C). Anionic microgels require the presence of multivalent cations (Ca²⁺) to promote the complexation, overcoming the electrostatic repulsion with negatively charged DNA. Then again, Langmuir monolayers evidence their complexation at the surface. However, the presence of Ca²⁺ seems to induce profound changes in the interaction and surface conformation of anionic microgels. These alterations are further explored by measuring adsorbed films with the pendant drop technique. Conformational changes induced by Ca²⁺ on the structure of the microgel can ultimately affect the complexation with DNA and should be considered in the design. The combination of microstructural and surface properties for microgels offers a new perspective into complexation of DNA with soft particles with biomedical applications. Full article

Stimuli-responsive microgels have recently attracted great attention in fundamental research as their soft particles can be deformed and compressed at high packing fractions resulting in singular phase behaviours. Moreover, they are also well suited for a wide variety of applications such as drug delivery, tissue engineering, organ-on-chip devices, microlenses fabrication and cultural heritage. Here, thermoresponsive and pH-sensitive cross-linked microgels, composed of interpenetrating polymer networks of poly(N-isopropylacrylamide) (PNIPAM) and poly(acrylic acid) (PAAc), are synthesized by a precipitation polymerization method in water and investigated through differential scanning calorimetry in a temperature range across the volume phase transition temperature of PNIPAM microgels. The phase behaviour is studied as a function of heating/cooling rate, concentration, pH and PAAc content. At low concentrations and PAAc contents, the network interpenetration does not affect the transition temperature typical of PNIPAM microgel in agreement with previous studies; on the contrary, we show that it induces a marked decrease at higher concentrations. DSC analysis also reveals an increase of the overall calorimetric enthalpy with increasing concentration and a decrease with increasing PAAc content. These findings are discussed and explained as related to emerging aggregation processes that can be finely controlled by properly changing concentration, PAAc content an pH. A deep analysis of the thermodynamic parameters allows to draw a temperature–concentration state diagram in the investigated concentration range. Full article

Microgels can be considered soft, porous and deformable particles with an internal gel structure swollen by a solvent and an average size between 100 and 1000 nm. Due to their biocompatibility, colloidal stability, their unique dynamicity and the permeability of their architecture, they are emerging as important candidates for drug delivery systems, sensing and biocatalysis. In clinical applications, the research on responsive microgels is aimed at the development of “smart” delivery systems that undergo a critical change in conformation and size in reaction to a change in environmental conditions (temperature, magnetic fields, pH, concentration gradient). Recent achievements in biodegradable polymer fabrication have resulted in new appealing strategies, including the combination of synthetic and natural-origin polymers with inorganic nanoparticles, as well as the possibility of controlling drug release remotely. In this review, we provide a literature review on the use of dual and multi-responsive chitosan-grafted-poly-(N-vinylcaprolactam) (CP) microgels in drug delivery and oncological applications. Full article

CBD is a promising candidate for treatment of many diseases and plays a major role in the growing trend to produce high-end drugs from natural, renewable resources. In the present work, we demonstrate a way to incorporate the anti-inflammatory drug CBD into smart microgel particles. The copolymer microgels that we chose as carrier systems exhibit a volume phase transition temperature of 39 ${}^{\circ }\mathrm{C}$, which is just above normal body temperature and makes them ideal candidates for hyperthermia treatment. While a simple loading route of CBD was not successful due to the enormous hydrophobicity of CBD, an alternative route was developed by immersing the microgels in ethanol. Despite the expected loss of thermoresponsive behaviour of the microgel matrix due to the solvent exchange, a temperature-dependent release of CBD was detected by the material, creating an interesting question of interactions between CBD and the microgel particles in ethanol. Furthermore, the method developed for loading of the microgel particles with CBD in ethanol was further improved by a subsequent transfer of the loaded particles into water, which proves to be an even more promising approach due to the successful temperature-dependent release of the drug above the collapse temperature of the microgels. Full article