Thermoreversible Gels Research Articles

Synthesis and Thermoreversible Gelation of Coil-Rod Copolymers with a Dendritic Polyethylene Core and Multiple Helical Poly(γ-benzyl-L-glutamate) Arms.

Coil-rod copolymers with a dendritic polyethylene (DPE) core and multiple helical poly(γ-benzyl-L-glutamate) (PBLG) arms (DPE-(PBLG)n) were prepared by palladium-catalyzed copolymerization in tandem with ring-opening polymerization (ROP). Macroinitiator (DPE-(NH2)11) was firstly prepared by the group transformation of DPE-(OH)11 generated from palladium-catalyzed copolymerization of ethylene and acrylate comonomer. Coil-helical DPE-(PBLG)11 copolymers were prepared by ROP of γ-benzyl-L-glutamate-N-carboxyanhydride (BLG-NCA). These DPE-(PBLG)11 copolymers could form thermoreversible gels in toluene solvent, and the dendritic topology of the DPE core increased the critical gelation concentrations. The self-assembled nanostructure of gels was fully characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), small-angle X-ray scattering (SAXS), and wide-angle X-ray diffraction (WAXD), and the morphology of the fibrous structure was a twisted flat ribbon through a self-assembled nanoribbon mechanism. The self-assembled fibers formed by DPE-(PBLG45)11 are more heterogeneous and ramified than previously observed fibers formed by PBLG homopolymer and block copolymers.

Mastering textural control in multi-polysaccharide gels: Effect of κ-carrageenan, konjac glucomannan, locust bean gum, low-acyl gellan gum, and sodium alginate

To comprehend the intricate interplay of five common food polysaccharides, κ-Carrageenan (KC), konjac glucomannan (KGM), locust bean gum (LBG), low-acyl gellan gum (LAG), and sodium alginate (SA), within composite polysaccharide gels, widely employed for textural modulation and flavor enhancement. This study systematically modulates the quantities of these five polysaccharides to yield six distinct multi-polysaccharide gels. The unique impact of each polysaccharide on the overall quality of composite gels were studied by thermostability, microstructure, water-holding capacity (WHC), texture, and sensory attributes. The findings unequivocally manifest the phenomenon of thermoreversible gelation in all composite gels, except for the KC-devoid sample, which displayed an inability to solidify. Notably, KGM, LBG, and LAG emerged as pivotal enhancers of the network structure in these composite gels, while SA was identified as a promotor of layered structure, resulting in a reduction of surface hardness. Leveraging principal component analysis (PCA) to analyzed 14 critical evaluation parameters of the five multi-polysaccharide gels, revealing the order as follows: KC > KGM > SA > LAG > LBG. These findings would imparts valuable insights into the pragmatic utilization of multi-polysaccharide gels for the development of food products (e.g. Bobo balls in milk tea) with tailored textural and sensory attributes.

Directional-Freezing-Enabled MXene Orientation toward Anisotropic PVDF/MXene Aerogels: Orientation-Dependent Properties of Hybrid Aerogels.

Polymer hybrid materials that contain reinforcements with a preferred orientation have received growing attention because of their unique properties and promising applications in multifunctional fields. Herein, anisotropic poly(vinylidene fluoride) (PVDF)/MXene hybrid aerogels with highly ordered delaminated MXene nanosheets and anisotropic porous structures were successfully fabricated by unidirectional freezing of thermoreversible gels followed by a freeze-drying process. The strong interfacial interactions between PVDF chains and abundant functional groups on the surface of MXene enabled the orientation of MXene nanosheets at the boundaries of ice crystals as the semicrystalline PVDF and delaminated MXene nanosheets are squeezed along the freezing direction. These aerogels display distinct properties along the freezing and perpendicular to the freezing (transverse) directions. These anisotropic aerogels are flexible and flame-retardant and possess an anisotropic compression performance, heat transfer, electrical conductivity, and electromagnetic interference (EMI) shielding. Further, by increasing the MXene loadings, the electrical conductivity and EMI shielding performances of hybrid aerogels were significantly improved. The PVDF aerogel showed sticky hydrophobicity with a contact angle of 139°, whereas the contact angle increased significantly in hybrid aerogels (153°) with low water adhesion, making them suitable as self-cleaning materials. The combination of the above characteristics makes these hybrid aerogels potential candidates for a wide range of electronic applications.

Thermoreversible Gelation with Supramolecularly Polymerized Cross-Link Junctions.

Structure and reversibility of cross-link junctions play pivotal roles in determining the nature of thermoreversible gelation and dynamic mechanical properties of the produced polymer networks. We attempt to theoretically explore new types of sol-gel transitions with mechanical sharpness by allowing cross-links to grow without upper bound. We consider thermoreversible gelation of the primary molecules R{Af} carrying the number f of low molecular weight functional groups (gelators) A. Gelators A are assumed to form supramolecular assemblies. Some examples are: telechelic polymers (f=2) carrying π-π stacking benzene derivatives at their both ends, and trifunctional star molecules (f=3) bearing multiple hydrogen-bonding gelators. The sol-gel transition of the primary molecules becomes sharper with the cooperativity parameter of the stepwise linear growth of the cross-links. There is a polymerization transition (crossover without singularity) of the junctions in the postgel region after the gel point is passed. If the gelator A tends to form supramolecular rings competitively with linear chains, there is another phase transition in the deep postgel region where the average molecular weight of the rings becomes infinite (Bose-Einstein condensation of rings). As a typical example of binary cross-links where gelators A and B form mixed junctions, we specifically consider metal-coordinated binding of ligands A by metal ions B. Two types of multi-nuclear supramolecular complexes are studied: (i) linear stacking (ladder) of the sandwich A2B units, and (ii) linear train of egg-box A4B units. To find the strategy towards experimental realization of supramolecular cross-links, the average molecular weight, the gel fraction, the average length of the cross-link junctions are numerically calculated for all of these models as functions of the functionality f, the concentration of the solute molecules, and the temperature. Potential candidates for the realization of these new types of thermoreversible gelation are discussed.

Modification of mechanical, rheological and structural properties of agar hydrogel using xanthan and locust bean gum

Agar is a valuable seaweed hydrocolloid that can form a high-firmness thermoreversible gel. With the increasing demand for vegetarian meals, agar can be used as a gelatin substitute with some modifications. In this study, we investigated the structural, mechanical, and rheological properties of a compound hydrogel using the agar/locust bean/xanthan gum (ALX). The different concentrations of hydrocolloids were optimized based on comparing the results of texture profile analysis of samples with high-bloom gelatin. Fourier transform infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy tests confirmed the interaction between agar, locust bean and xanthan gum. The textural analysis results showed that the addition of locust bean gum (LBG) and xanthan gum (XG) to agar could significantly increase the springiness of agar hydrogel (AG) from 0.92 ± 0.00 to 1.00 ± 0.00, also decrease its hardness from 702.11 ± 5.99 to 343.31 ± 20.23 g (p < 0.05). Moreover, a remarkable decrease was shown in the syneresis degree of AG from 2.33 ± 0.02% to 0.52 ± 0.00%. All behaviors of the optimum hydrogel indicated the effective interaction of LBG and XG with AG which made the final compound hydrogel a promising alternative to high-bloom gelatin.

Methyl Cellulose based in situ Hydrogel for Controlled Drug Delivery and Tissue Engineering Application

Methyl cellulose is an attractive smart biomaterial for its thermoreversible gelation nature. When subjected to temperature stimuli, an aqueous solution containing methyl cellulose at a critical concentration exhibits the ability to form stable physically cross-linked hydrogels. These hydrogels alter the physico-chemical and mechanical properties of the methyl cellulose. This thermo-responsive nature become quite appealing when the physiological temperature functions as a trigger to regulate the thermogelation of methyl cellulose. Regarding this, exciting inventions have been explored in the drug delivery and tissue engineering field which make methyl cellulose an attractive and versatile biomaterial. In this review, we have covered traditional and advanced applications of methyl cellulose as thermoreversible in situ gelling system. Three main types of applications are presented: (i) in situ gelling system for controlled drug delivery; (ii) fabrication of injectable scaffolds and cell sheet for tissue engineering application; and finally (iii) developing methyl cellulose based bioink for 3D bioprinting by applying in situ thermogelation property of methyl cellulose.

Toughening colloidal gels using rough building blocks

Colloidal gels, commonly used as mesoporous intermediates or functional materials, suffer from brittleness, often showing small yield strains on the order of 1% or less for gelled colloidal suspensions. The short-range adhesive forces in most such gels are central forces—combined with the smooth morphology of particles, the resistance to yielding and shear-induced restructuring is limited. In this study, we propose an innovative approach to improve colloidal gels by introducing surface roughness to the particles to change the yield strain, giving rise to non-central interactions. To elucidate the effects of particle roughness on gel properties, we prepared thermoreversible gels made from rough or smooth silica particles using a reliable click-like-chemistry-based surface grafting technique. Rheological and optical characterization revealed that rough particle gels exhibit enhanced toughness and self-healing properties. These remarkable properties can be utilized in various applications, such as xerogel fabrication and high-fidelity extrusion 3D-printing, as we demonstrate in this study.

Gels of Semiconducting Polymers in Benign Solvents.

Gels of semiconducting polymers have many potential applications, including biomedical devices and sensors. Here, we report a self-assembled gel system consisting of isoindigo-based semiconducting polymers with galactose side chains in benign, alcohol-based solvents. Because of the carbohydrate side chains, the modified isoindigo polymers are soluble in alcohols. We obtained thermoreversible gels in 1-propanol using these polymers and di-Fmoc-l-lysine, a molecular gelator. The polymers and molecular gelators have been selected in such a way that they do not have significant physical interactions. The molecular gelator self-assembled to form a fibrous structure that confines the polymer chains in the interstitial spaces of the fibers. The polymer chains formed local aggregations and increased the shear moduli of the gels significantly. Bulky galactose side chains and the less planar nature of the polymer backbone hindered the formation of long-range assembled structures of the polymers. However, the dispersion of polymers throughout the gel samples resulted in a percolated structure in the dried gel films. The bulk electrical conductivity of dried gels confirmed the presence of such percolated structures. Our results demonstrated that carbohydrate-containing conjugated polymers can be combined with molecular gelators to obtain gels in eco-friendly solvents.

From Seaweeds to Hydrogels: Recent Progress in Kappa-2 Carrageenans.

Hybrid carrageenans, also called kappa-2 (K2) or weak kappa, are a class of sulfated polysaccharides with thermo-reversible gelling properties in water and are extracted from a specific family of red seaweeds. K2 are known in the industry for their texturizing properties which are intermediate between those of kappa-carrageenans (K) and iota-carrageenans (I). As such, K2 are gaining industrial interest, as they can replace blends of K and I (K + I) in some niche applications. Over the last decade or so, some progress has been made in unravelling K2's chemical structure. The understanding of K2 gel's structure-rheological properties' relationships has also improved. Such recent progress is reported here, reviewing the literature on gelling K2 published since the last review on the topic. The focus is on the seaweeds used for extracting K2, their block copolymer chemical structures, and how these impact on the gel's formation and rheological properties. The outcome of this review is that additional rheological and structural studies of K2 hydrogels are needed, in particular to understand their viscoelastic behavior under large deformation and to unravel the differences between the texturizing properties of K2 and K + I.

Preparation of xerogel based on syndiotactic polystyrene (sPS)/MWCNTs hybrid polymer gel for application as a dielectric material with high dielectric permittivity

MWCNTs were dispersed in sPS gel in both pristine as well as functionalized form to observe its effect on structure, morphology, thermal as well as dielectric properties of the resulting hybrid polymer gel. Since, the ortho-xylene induces clathration in pure sPS polymer in α-phase leading to thermoreversible gelation resulting in the δ-crystalline phase (sPS gel). Therefore, the removal of solvent from solvated δ-crystalline phase gives non-solvated δe-crystalline phase (sPS xerogel). The three dimensional fibrillar networks, as observed with scanning electron microscopy (SEM) and atomic force microscopy (AFM), have the polymer chains with s(2/1)2 helical conformation which makes the gel elastic. Fourier transform infra red spectroscopy (FTIR) shows the conformation change from trans planar to s(2/1)2 helical as indicated by the disappearance of peak at 541 cm−1 and appearance of peak at 537 cm−1 and 571 cm−1. The peak at 7.9° confirms the δ-crystalline phase presence whereas the absence of solvent is indicated by peak absence at 10°. Differential scanning calorimetry (DSC) thermogram confirms the δ to γ phase transition in the 100–150 °C temperature range. As we get an intermingled structure of gel fibers and MWCNTs, therefore, the dielectric behavior showed the percolative nature of the hybrid sPS xerogel. The pure sPS xerogel displayed no response to the frequency change whereas due to interfacial polarization, hybrid sPS xerogel responded to frequency change.

A smart low-molecular-mass naphthalene-pyrazoline gelator: Gelation behavior and selective fluorescent detection Cu2+

A smart low-molecular-mass organic gelator based on naphthalene-pyrazoline has been designed and synthesized. The gelator G can form a thermo reversible stable gel in tert-butanol, cyclohexane, cyclohexanol, and DMSO through self-assembly, it emits blue and yellow-green fluorescence under ultraviolet radiation. Notably, it has multiple stimulus responses of light, heat, shock and ion. In addition, it could act as an efficient fluorescent probe for the selective sensing of Cu2+ in the solution containing water. The detection limit of Cu2+ in THF deionized aqueous solution (V:V = 9:1) is 5.65 × 10−8 M. The complex ratio of G to Cu2+ is 1:1. In addition, the G has good biocompatibility in living cells.

Thermoresponsive Gel-loaded Oxcarbazepine Nanosystems for Nose- To-Brain Delivery: Enhanced Antiepileptic Activity in Rats

BackgroundOxcarbazepine (OXC) is a frequently prescribed antiepileptic drug for managing focal and generalized seizures. Its therapeutic benefits are limited by its dose-dependent side effects. Nose-to-brain delivery is a novel route for improving the efficacy of antiepileptics. Drug encapsulation in mucoadhesive nanoparticles offers even more advantages for the nasal route.ObjectiveThe study aimed to develop oxcarbazepine-loaded chitosan nanoparticles (OXC-NP) added to a mucoadhesive thermo-reversible gel for intranasal delivery and enhancement of antiepileptic activity.MethodsThe formulation was optimized based on entrapment efficiency, polydispersity index, particle size, zeta potential, and in vitro release analysis. The therapeutic efficacy of OXC-NP was assessed in an epileptic rat model and compared to intranasal OXC and oral OXC.ResultsThe optimized OXC-NPs with chitosan exhibited particle size, zeta potential, and entrapment efficiency of 189 nm, + 31.4 mV ± 2.5 and 97.6% ± 0.14, respectively. The release of OXC was prolonged, reaching 47.1% after 6 h and 55% after 24 h. Enhanced antiepileptic activity of OXC-NP was manifested as decreased seizure score and prolonged survival. Halting of hippocampal TNF-α and IL-6 together with upregulated IL-10 could explain its anti-inflammatory mechanisms.ConclusionsIntranasal OXC-NP-loaded in situ gel represents a promising formulation for enhanced antiepileptic potential achieved at low drug concentrations.

Thermoreversible Gels Based on Chitosan Copolymers as "Intelligent" Drug Delivery System with Prolonged Action for Intramuscular Injection.

Thermosensitive gels based on copolymers (PEG-chitosan, chitosan-polyethylenimine, chitosan-arginine and glycol-chitosan-spermine) are presented as promising polycations for the formation of DNA polyplexes and the potential for the development of drugs with prolonged release (up to 30 days). Being in liquid form at room temperature, such compounds can be injected into muscle tissue with rapid gel formation at human body temperature. An intramuscular depot is formed with a therapeutic agent that provides a gradual release of the drug, such as an antibacterial or cytostatic. The physico-chemical parameters of the formation of polyplexes between polycationic polymers of various compositions and molecular architecture and DNA were studied via FTIR, UV-vis and fluorescence spectroscopy using the dyes rhodamine 6G (R6G) and acridine orange (AO). The competitive displacement of AO from AO-DNA complexes showed that, with a ratio of N/P = 1, most of the DNA is bound to a polycation. During the formation of polyplexes, the DNA charge is neutralized by a polycation, which is reflected in electrophoretic immobility. The cationic polymers described in this work at a concentration of 1-4% are capable of forming gels, and the thermoreversible property is most characteristic of pegylated chitosan. BSA, as a model anionic molecule, is released by half in 5 days from the Chit5-PEG5 gel; full release is achieved in 18-20 days. At the same time, in 5 days, the gel is destroyed up to 30%, and in 20 days, by 90% (release of chitosan particles). For the first time, flow cytometry was used to study DNA polyplexes, which showed the existence of fluorescent particles in a much larger number in combination with free DNA. Thus, functional stimulus-sensitive polymers are potentially applicable for the creation of prolonged therapeutic formulations for gene delivery systems, which were obtained. The revealed regularities appear to be a platform for the design of polyplexes with controllable stability, in particular, fulfilling the requirements imposed for gene delivery vehicles.

Features of the rheological behavior of aqueous solutions of alumino-, aluminoboro- and aluminochromophosphates

Rheological studies carried out using rotational rheometer in the rotational and oscillatory modes at different temperatures and heating/cooling conditions revealed that the aqueous solutions of alumino-, aluminoboro- and aluminochromophosphates presented an unusual behavior. The largest increase in the viscosity of the studied systems was determined between 20 and 60 °C and was attributed to the formation of thermo-reversible inorganic gels in solutions of aluminophosphates due to interionic association. At the same time, the oscillation mode was found to be more sensitive to the process of polymer gel formation compared to the rotation mode. In addition, the process of polymer gel formation was more adequately studied from dynamic tests.

Characterization of Agarose Gels in Solvent and Non-Solvent Media.

Agarose is known to form a homogeneous thermoreversible gel in an aqueous medium over a critical polymer concentration. The solid-liquid phase transitions are thermoreversible but depend on the molecular structure of the agarose sample tested. The literature has mentioned that agarose gels could remain stable in non-solvents such as acetone or ethanol. However, there has been no characterization of their behavior nor a comparison with the gels formed in a good solvent such as water. In the first step of this article, the structure was characterized using 1H and 13C NMR in both D2O and DMSO-d6 solvents. DMSO is a solvent that dissolves agarose regardless of the temperature. First, we have determined a low yield of methyl substitution on the D-galactose unit. Then, the evolution of the 1H NMR spectrum was monitored as a function of temperature during both increasing and decreasing temperature processes, ranging from 25 to 80 °C. A large thermal hysteresis was obtained and discussed, which aided in the interpretation of rheological behavior. The hysteresis of NMR signals is related to the mobility of the agarose chains, which follows the sol/gel transition depending on the chains' association with H-bonds between water and the -OH groups of agarose for tightly bound water and agarose/agarose in chain packing. In the second step of the study, the water in the agarose gel was exchanged with ethanol, which is a non-solvent for agarose. The resulting gel was stable, and its properties were characterized using rheology and compared to its behavior in aqueous media. The bound water molecules that act as plasticizers were likely removed during the exchange process, resulting in a stronger and more brittle gel in ethanol, with higher thermal stability compared to the aqueous gel. It is the first time that such gel is characterized without phase transition when passing from a good solvent to a non-solvent. This extends the domains of application of agarose.

Transparent thermoreversible gels of β-(1 → 6)-branched β-(1 → 3)-glucan derived from the cauliflower mushroom Sparassis crispa

Sparassis crispa is an edible mushroom and its purée forms a thermoreversible cold-setting gel. In the present study, the gel component was extracted and was analyzed by NMR. The gel component had the same primary structure as reported for the β-glucan of schizophyllan or scleroglucan, with β-(1 → 3)-linked glucose as the main chain and every three residues containing a β-(1 → 6)-linked glucose. Large deformation test of this β-glucan gel at 4 °C showed fracture at a strain of approximately 60% in the concentration range from 1.8 to 2.0 wt %. The β-glucan above a critical molecular weight appears to be required for gel formation.

Evaluation of ionic calcium and protein concentration on heat- and cold-induced gelation of whey protein isolate gels as a potential food formulation for 3D food printing

3D food printing (3DFP) is an innovative food process, but developing foods with ideal printability can prove challenging. Whey protein isolate (WPI) gels can be difficult to print due to their rigidity. This study evaluated the cold- and heat-induced gelation properties of WPI for use in 3DFP. Initially, the effect of WPI concentration ([WPI]) (8–12% (w/w)) and ionic calcium concentration ([Ca2+]) (0–8 mM) was evaluated on the heat-induced gelation capability and thermal reversibility. Treatments were categorised into three groups: thermo-irreversible, thermo-reversible, and non-gelling. Non-gelling treatments were used for cold-induced gelation by mixing the denatured WPI solution with 150 mM Ca2+ solution. Thermo-reversibility and cold-induced gelation properties were assessed using oscillatory rheometry. Finally, thermo-irreversible gels (TIRG) were characterised using extrudability and texture profile analysis. The thermo-reversible gels had an unsuitable range of G' (5–60 Pa) and δ (40–60°) for obtaining a self-standing object. Cold gelation using [WPI] = 10%, G' > 500 Pa and δ < 10°, may be suitable for 3DFP but requires an adapted extrusion-based 3D printer, i.e., co-extrusion, cooling or support bath. The extrusion force of TIRG decreased during heating and was mainly affected by [WPI]. Upon re-cooling, the force recovered (>85%) with the addition of [Ca2+] > 4 mM. TIRG using the following treatments [WPI]-[Ca2+] = 12% - 2 mM, 11% - 4 mM, and 10% - 6 mM demonstrated good printability. Principal component analysis showed TIRG with low hardness, resilience, and extrusion force loss during heating are potentially suitable for 3DFP.

Controlled Swelling of Monolithic Films as a Facile Approach to the Synthesis of UHMWPE Membranes

A new method of fabricating porous membranes based on ultra-high molecular weight polyethylene (UHMWPE) by controlled swelling of the dense film was proposed and successfully utilized. The principle of this method is based on the swelling of non-porous UHMWPE film in organic solvent at elevated temperatures, followed by its cooling and further extraction of organic solvent, resulting in the formation of the porous membrane. In this work, we used commercial UHMWPE film (thickness 155 μm) and o-xylene as a solvent. Either homogeneous mixtures of the polymer melt and solvent or thermoreversible gels with crystallites acting as crosslinks of the inter-macromolecular network (swollen semicrystalline polymer) can be obtained at different soaking times. It was shown that the porous structure and filtration performance of the membranes depended on the swelling degree of the polymer, which can be controlled by the time of polymer soaking in organic solvent at elevated temperature (106 °C was found to be the optimal temperature for UHMWPE). In the case of homogeneous mixtures, the resulting membranes possessed both large and small pores. They were characterized by quite high porosity (45-65% vol.), liquid permeance of 46-134 L m-2 h-1 bar-1, a mean flow pore size of 30-75 nm, and a very high crystallinity degree of 86-89% at a decent tensile strength of 3-9 MPa. For these membranes, rejection of blue dextran dye with a molecular weight of 70 kg/mol was 22-76%. In the case of thermoreversible gels, the resulting membranes had only small pores located in the interlamellar spaces. They were characterized by a lower crystallinity degree of 70-74%, a moderate porosity of 12-28%, liquid permeability of up to 12-26 L m-2 h-1 bar-1, a mean flow pore size of up to 12-17 nm, and a higher tensile strength of 11-20 MPa. These membranes demonstrated blue dextran retention of nearly 100%.

Formation of thermo-reversible gels from whey proteins after combined thermal and ethanol pretreatment

Τhis study investigates the ability of whey proteins, which were pre-treated with ethanol (0–70%) and subjected tothermal treatment (70 °C for 60 min), to form thermo-reversible gels after removing the alcohol through freeze-drying. The ethanol-free gels were monitored by means of rheology and confocal laser scanning microscopy. Moreover, the role of ethanol during heating of whey proteins was investigated by UV difference spectroscopy. The results showed a retention of the denatured character (30–35%) of whey proteins after removal of ethanol, regardless of whether heating was applied. Intermolecular disulfide connections increased in whey protein solutions pretreated with 30 and 50% w/w ethanol. The determination of free –SH groups demonstrated that their number was increased by heating in the presence of ethanol and after ethanol's removal. Dynamic rheological measurements showed that ethanol-free gels, previously heated with 50% w/w ethanol, formed thermo-reversible gels upon cooling to 5 °C and exhibited significantly higher storage modulus values (G’∼300 Pa) than the counterparts without pretreatment of the proteins with ethanol (G’ = 0.0002 Pa). Generally, the partial retention of the denaturing effect of ethanol on whey proteins after its removal and their ability to form thermo-reversible gels could lead to new applications in the food and pharmaceutical industries.

Design and Evaluation of Paeonol-Loaded Liposomes in Thermoreversible Gels for Atopic Dermatitis.

Paeonol (PAE) is a hydrophobic drug. In this study, we encapsulated paeonol in a lipid bilayer of liposomes (PAE-L), which delayed drug release and increased drug solubility. When PAE-L was dispersed in gels (PAE-L-G) based on a poloxamer matrix material for local transdermal delivery, we observed amphiphilicity, reversible thermal responsiveness, and micellar self-assembly behavior. These gels can be used for atopic dermatitis (AD), an inflammatory skin disease, to change the surface temperature of the skin. In this study, we prepared PAE-L-G at an appropriate temperature for the treatment of AD. We then assessed the gel's relevant physicochemical properties, in vitro cumulative drug release, and antioxidant properties. We found that PAE-loaded liposomes could be designed to increase the drug effect of thermoreversible gels. At 32 °C, PAE-L-G could change from solution state to gelatinous state at 31.70 ± 0.42 s, while the viscosity was 136.98 ± 0.78 MPa.S and the free radical scavenging rates on DPPH and H2O2 were 92.24 ± 5.57% and 92.12 ± 2.71%, respectively. Drug release across the extracorporeal dialysis membrane reached 41.76 ± 3.78%. In AD-like mice, PAE-L-G could also relieve skin damage by the 12th day. In summary, PAE-L-G could play an antioxidant role and relieve inflammation caused by oxidative stress in AD.