Corrigendum: Glutamatergic and GABAergic neurons in the preoptic area of the hypothalamus play key roles in menopausal hot flashes.

[This corrects the article DOI: 10.3389/fnagi.2022.993955.].

Thermo-activated in situ rectal gel preparation for Ibuprofen using eutectic mixture.

This study aimed to develop a thermosensitive in situ gel formulation for rectal delivery of Ibuprofen as an efficient alternative dosage form. Utilizing poloxamer 188, poloxamer 407, and HPMC via cold technique method, a thermosensitive in situ gel was successfully prepared. The concentration of Ibuprofen in the formulations was 1.2 % (w/w). The prepared gels underwent assessment for clarity, gelation temperature, gelation time, gel strength, spread ability, syringe-ability, pH, viscosity, FTIR, and drug content. The selected formulations exhibited a gelation temperature within the range of 30 °C to 36 °C, with consistent amount of drug soluble in the formulations (93 % - 110 %). Mucoadhesive studies, in vitro release tests, ex vivo modeling of drug release, kinetic studies modeling, and histopathology testing were also conducted. The formulation comprising 18 % poloxamer 407, 12 % poloxamer 188, and 1 % sodium chloride (FS15) demonstrated suitable gelation temperature and desirable drug release rate. In vitro drug release tests indicated completion within one hour for both FS10 (20 % P407 & 10 % P188) and FS15 (18 % P407 & 12 % P188), with consistent and predictable release patterns observed through kinetic modeling analysis. Microscopic histopathology examination confirmed the safety of the selected formula, exhibiting no irritation in the mucosal membrane of the sheep. In conclusion, Ibuprofen thermosensitive in situ gel presents a promising and convenient strategy as a rectal carrier and an alternative dosage form to solid suppositories.

Temperature-responsive hydrogel-grafted vessel-on-a-chip: Exploring cold-induced endothelial injury.

Cold-induced vasoconstriction is a significant contributor that leads to chilblains and hypothermia in humans. However, current animal models have limitations in replicating cold-induced acral injury due to their low sensitivity to cold. Moreover, existing in vitro vascular chips composed of endothelial cells and perfusion systems lack temperature responsiveness, failing to simulate the vasoconstriction observed under cold stress. This study presents a novel approach where a microfluidic bioreactor of vessel-on-a-chip was developed by grafting the inner microchannel surface of polydimethylsiloxane with a thermosensitive hydrogel skin composed of N-isopropyl acrylamide and gelatin methacrylamide. With a lower critical solution temperature set at 30°C, the gel layer exhibited swelling at low temperatures, reducing the flow rate inside the channel by 10% when the temperature dropped from 37°C to 4°C. This well mimicked the blood stasis observed in capillary vessels in vivo. The vessel-on-a-chip was further constructed by culturing endothelial cells on the surface of the thermosensitive hydrogel layer, and a perfused medium was introduced to the cells to provide a physiological shear stress. Notably, cold stimulation of the vessel-on-a-chip led to cell necrosis, mitochondrial membrane potential (ΔΨm) collapse, cytoskeleton disaggregation, and increased levels of reactive oxygen species. In contrast, the static culture of endothelial cells showed limited response to cold exposure. By faithfully replicating cold-induced endothelial injury, this groundbreaking thermosensitive vessel-on-a-chip technology offers promising advancements in the study of cold-induced cardiovascular diseases, including pathogenesis and therapeutic drug screening.

Stem Cell-Derived Extracellular Vesicle-Bearing Injectable Hydrogel for Collagen Generation in Dermis.

Despite the remarkable advances of dermal fillers that reduce wrinkles caused by dermis thickness reduction, they still lack effective hydrogel systems that stimulate collagen generation along with injection convenience. Here, we develop a stem cell-derived extracellular vesicle (EV)-bearing thermosensitive hydrogel (EVTS-Gel) for effective in vivo collagen generation. The TS-Gel undergoes sol-gel transition at 32.6 °C, as demonstrated by the storage and loss moduli crossover. Moreover, the TS-Gel and the EVTS-Gel have comparable rheological properties. Both hydrogels are injected in a sol state; hence, they require lower injection forces than conventional hydrogel-based dermal fillers. When locally administered to mouse skin, the TS-Gel extends the retention time of EVs by 2.23 times. Based on the nature of the controlled EV release, the EVTS-Gel significantly inhibits the dermis thickness reduction caused by aging compared to the bare EV treatment for 24 weeks. After a single treatment, the collagen layer thickness of the EVTS-Gel-treated dermis becomes 2.64-fold thicker than that of the bare EV-treated dermis. Notably, the collagen generation efficacy of the bare EV is poorer than that of the EVTS-Gel of a 10× lesser dose. Overall, the EVTS-Gel shows potential as an antiaging dermal filler for in vivo collagen generation.

Coordinating Macrophage Targeting and Antioxidation by Injectable Nanocomposite Hydrogel for Enhanced Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA), an immune-mediated inflammatory disease, is characterized by a large number of infiltrated immune cells and abnormally elevated reactive oxygen species (ROS) in the joint. Various proinflammatory factors secreted by macrophages and the elevated ROS by inflammatory cells are deeply intertwined and together contribute to joint damage. Targeted and sustained anti-inflammation and antioxidation strategies are needed for RA treatment. To alleviate the oxidative stress and target the source of inflammatory cytokines, we developed a thermosensitive injectable hydrogel, Dex-DSLip/Cro@Gel, to coordinate the targeted anti-inflammatory and antioxidation effects. Within the injectable gel, dexamethasone (Dex)-loaded liposomes (Dex-DSLip), modified with dextran sulfate (DS), target macrophages via interaction with scavenger receptor A (SR-A). Simultaneously, crocin I (Cro) is loaded in the gel with a high loading capacity. The porous structure of Dex-DSLip/Cro@Gel successfully prolongs the retention time of both drugs and sustains the release of Dex and Cro. After intra-articular injection of Dex-DSLip/Cro@Gel in RA rats, the expression of inflammatory factors in the ankle joints was significantly reduced. Joint erythema and bone erosion were markedly alleviated. Through the synergistic effects of Dex and Cro, Dex-DSLip/Cro@Gel demonstrates targeted anti-inflammatory and antioxidation effects as well as mitigated bone erosion and long-term therapeutic effects for RA. This thermosensitive injectable nanocomposite hydrogel synergizes anti-inflammatory and antioxidation effects and targets the microenvironment in the joint, offering a new approach for RA treatment.

Thermosensitive Hydrogels as Targeted and Controlled Drug Delivery Systems: Potential Applications in Transplantation.

Drug delivery in transplantation plays a vital role in promoting graft survival, preventing rejection, managing complications, and contributing to positive patient outcomes. Targeted and controlled drug delivery can minimize systemic effects. Thermosensitive hydrogels, due to their unique sol-gel transition properties triggered by thermo-stimuli, have attracted significant research interest as a potential drug delivery system in transplantation. This review describes the current status, characteristics, and recent applications of thermosensitive hydrogels for drug delivery. Studies aimed at improving allotransplantation outcomes using thermosensitive hydrogels are then elaborated on. Finally, the challenges and opportunities associated with their use are discussed. Understanding the progress of research will serve as a guide for future improvements in their application as a means of targeted and controlled drug delivery in translational therapeutic applications for transplantation.

Injectable vancomycin-loaded silk fibroin/methylcellulose containing calcium phosphate-based in situ thermosensitive hydrogel for local treatment of osteomyelitis: Fabrication, characterization, and in vitro performance evaluation.

The conventional treatment of osteomyelitis with antibiotic-loaded nondegradable polymethylmethacrylate (ATB-PMMA) beads has certain limitations, including impeded bone reconstruction and the need for secondary surgery. To overcome this challenge, this study aimed to develop and characterize an injectable vancomycin-loaded silk fibroin/methylcellulose containing calcium phosphate-based in situ thermosensitive hydrogel (VC-SF/MC-CAPs). The VC-SF/MC-CAPs solution can be easily administered at room temperature with a low injectability force of ≤30 N and a high vancomycin (VC) content of ~96%. Additionally, at physiological temperature (37 °C), the solution could transform into a rigid hydrogel within 7 minutes. In vitro drug release performed under both physiological (pH 7.4) and infection conditions (pH 4.5) revealed a prolonged release pattern of VC-SF/MC-CAPs following the Peppas-Sahlin kinetic model. In addition, the released VC from VC-SF/MC-CAPs hydrogels exhibited antibacterial activity against Staphylococcus aureus for a period exceeding 35 days, as characterized by the disk diffusion assay. Furthermore, at pH 7.4, the VC-SF/MC-CAPs demonstrated >60% degradation within 35 days. Importantly, when exposed to physiological pH conditions, CAPs are transformed into bioactive hydroxyapatite, which benefits bone formation. Therefore, VC-SF/MC-CAPs showed significant potential as a local drug delivery system for treating osteomyelitis.

Synergistic effects of thermosensitive liposomal doxorubicin, mild hyperthermia, and radiotherapy in breast cancer management: an orthotopic mouse model study.

Liposome formulations of the cancer drug doxorubicin have been developed to address the severe side effects that result from administration of this drug in a conventional formulation. Among them, thermosensitive liposomal doxorubicin presents enhanced tumor targeting and efficient drug release when combined with mild hyperthermia localized to the tumor site. Exploiting the radiosensitizing benefits of localized thermal therapy, the integration of radiation therapy with the thermally activated liposomal system is posited to amplify the anti-tumor efficacy. This study explored a synergistic therapeutic strategy that combines thermosensitive liposomal doxorubicin, mild hyperthermia, and radiotherapy, using an orthotopic murine model of breast cancer. The protocol of sequential multi-modal treatment, incorporating low-dose chemotherapy and radiotherapy, substantially postponed the progression of primary tumor growth in comparison to the application of monotherapy at elevated dosages. Improvements in unheated distant lesions were also observed. Furthermore, the toxicity associated with the combination treatment was comparable to that of either thermosensitive liposome treatment or radiation alone at low doses. These outcomes underscore the potential of multi-modal therapeutic strategies to refine treatment efficacy while concurrently diminishing adverse effects in the management of breast cancer, providing valuable insight for the future refinement of thermosensitive liposomal doxorubicin applications.

Recent advances on thermosensitive hydrogels-mediated precision therapy.

Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites, increased therapeutic efficacy, and reduced adverse effects. Over the past few years, sprayable or injectable thermosensitive hydrogels have exhibited high therapeutic potential. These can be applied as cell-growing scaffolds or drug-releasing reservoirs by simply mixing in a free-flowing sol phase at room temperature. Inspired by their unique properties, thermosensitive hydrogels have been widely applied as drug delivery and treatment platforms for precision medicine. In this review, the state-of-the-art developments in thermosensitive hydrogels for precision therapy are investigated, which covers from the thermo-gelling mechanisms and main components to biomedical applications, including wound healing, anti-tumor activity, osteogenesis, and periodontal, sinonasal and ophthalmic diseases. The most promising applications and trends of thermosensitive hydrogels for precision therapy are also discussed in light of their unique features.

GLUTAMYL-tRNA SYNTHETASE 1 deficiency confers thermo-sensitive male sterility in rice by affecting ROS homeostasis.

Temperature is one of the key environmental factors influencing crop fertility and yield. Understanding how plants sense and respond to temperature changes is, therefore, crucial for improving agricultural production. In this study, we characterized a temperature-sensitive male-sterile mutant in rice (Oryza sativa), glutamyl-tRNA synthetase 1-2 (ers1-2), that shows reduced fertility at high temperatures and restored fertility at low temperatures. Mutation of ERS1 resulted in severely delayed pollen development and meiotic progression at high temperatures, eventually leading to male sterility. Moreover, meiosis-specific events, including synapsis and crossover formation, were also delayed in ers1-2 compared with the wild type. However, these defects were all mitigated by growing ers1-2 at low temperatures. Transcriptome analysis and measurement of ascorbate, glutathione, and hydrogen peroxide (H2O2) contents revealed that the delayed meiotic progression and male sterility in ers1-2 were strongly associated with changes in reactive oxygen species (ROS) homeostasis. At high temperatures, ers1-2 exhibited decreased accumulation of ROS scavengers and overaccumulation of ROS. In contrast, at low temperatures, the antioxidant system of ROS was more active, and ROS contents were lower. These data suggest that ROS homeostasis in ers1-2 is disrupted at high temperatures but restored at low temperatures. We speculate that ERS1 dysfunction leads to changes in ROS homeostasis under different conditions, resulting in delayed or rescued meiotic progression and thermosensitive male fertility. ers1-2 may hold great potential as a thermosensitive material for crop heterosis breeding.

Injectable chitosan-polyvinylpyrrolidone composite thermosensitive hydrogels with sustained submucosal lifting for endoscopic submucosal dissection.

To develop a submucosal injection material with sustained submucosal lifting for endoscopic submucosal dissection (ESD), this study designed and prepared a novel composite thermosensitive hydrogel system with high pH chitosan-polyvinylpyrrolidone-ß-glycerophosphate (HpHCS-PVP-GP). HpHCS improved the injectability of the hydrogels and retained the rapid gelation ability at low concentrations. The modification of PVP significantly improved the stability of low-temperature hydrogel precursor solutions and the integrity of hydrogels formed at 37 °C through hydrogen bonds between PVP and HpHCS. A mathematical model was established using response surface methodology (RSM) to evaluate the synergistic effect of HpHCS, GP, and PVP concentrations on gelation time. This RSM model and submucosal lifting evaluation using in vitro pig esophageal models were used to determine the optimal formula of HpHCS-PVP-GP hydrogels. Although the higher PVP concentration (5 % (w/v)) prolonged gelation time, it improved hydrogel mechanical strength, resulting in better submucosal lifting performance. The experiments of Bama mini pigs showed that the heights of the cushions elevated by the HpHCS-5%PVP-GP hydrogel remained about 80 % 1 h after injection. Repeated injections were avoided, and the hydrogel had no cytotoxicity after electric cutting. Therefore, the HpHCS-PVP-GP thermosensitive hydrogel might be a promising submucosal injection material for ESD.

Study of the Thermal Phase Transition of Poly(N,N-diethylacrylamide-co-N-ethylacrylamide) Random Copolymers in Aqueous Solution.

N-alkyl-substituted polyacrylamides exhibit a thermal coil-to-globule transition in aqueous solution driven by an increase in hydrophobic interactions with rising temperature. With the aim of understanding the role of N-alkyl substituents in the thermal transition, this study focuses on the molecular interactions underlying the phase transition of poly(N,N-diethylacrylamide-co-N-ethylacrylamide) random copolymers. Poly(N,N-diethylacrylamide) (PDEAm), poly(N-ethylacrylamide) (PNEAm), and their random copolymers were synthesized by free radical polymerization and their chemical structure characterized spectroscopically. It was found that the values of the cloud-point temperature increased with PNEAm content, and particle aggregation processes took place, increasing the negative charge density on their surface. The cloud-point temperature of each copolymer decreased with respect to the theoretical values calculated assuming an absence of interactions. It is attributed to the formation of intra- and interchain hydrogen bonding in aqueous solutions. These interactions favor the formation of more hydrophobic macromolecular segments, thereby promoting the cooperative nature of the transition. These results definitively reveal the dominant mechanism occurring during the phase transition in the aqueous solutions of these copolymers.

Nanoarchitectonics and Biological Properties of Nanocomposite Thermosensitive Chitosan Hydrogels Obtained with the Use of Uridine 5'-Monophosphate Disodium Salt.

Currently, an important group of biomaterials used in the research in the field of tissue engineering is thermosensitive chitosan hydrogels. Their main advantage is the possibility of introducing their precursors (sols) into the implantation site using a minimally invasive method-by injection. In this publication, the results of studies on the new chitosan structures in the form of thermosensitive hydrogels containing graphene oxide as a nanofiller are presented. These systems were prepared from chitosan lactate and chitosan chloride solutions with the use of a salt of pyrimidine nucleotide-uridine 5'-monophosphate disodium salt-as the cross-linking agent. In order to perform the characterization of the developed hydrogels, the sol-gel transition temperature of the colloidal systems was first determined based on rheological measurements. The hydrogels were also analyzed using FTIR spectroscopy and SEM. Biological studies assessed the cytotoxicity (resazurin assay) and genotoxicity (alkaline version of the comet assay) of the nanocomposite chitosan hydrogels against normal human BJ fibroblasts. The conducted research allowed us to conclude that the developed hydrogels containing graphene oxide are an attractive material for potential use as scaffolds for the regeneration of damaged tissues.

Injectable nano-in situ-thermosensitive-hydrogels based on halofuginone and silver for postoperative treatment against triple-negative breast cancer.

Postoperative distant metastasis and high recurrence rate causes a dilemma in treating triple-negative breast cancer (TNBC) owing to its unforeseeable invasion into various organs or tissues. The wealth of nutrition provided by vascular may facilitate the proliferation and angiogenesis of cancer cells, which further enhance the rates of postoperative metastasis and recurrence. Chemotherapy, as a systemic postoperative adjuvant therapy, is generally applied to diminish recurrence and metastasis of TNBC. Herein, an halofuginone-silver nano thermosensitive hydrogel (HTPM&AgNPs-gel) was prepared via a physical swelling method. The in vitro anticancer efficacy of HTPM&AgNPs-gel was analyzed by investigating cell proliferation, migration, invasion, and angiogenesis capacity. Furthermore, the in vivo anti-cancer activity of HTPM&AgNPs-gel was further appraised through the tumor suppression, anti-metastatic, anti-angiogenic, and anti-inflammatory ability. The optimized HTPM&AgNPs-gel, a thermosensitive hydrogel, showed excellent properties, including syringeability, swelling behavior, and a sustained release effect without hemolysis. In addition, HTPM&AgNPs-gel was confirmed to effectively inhibit the proliferation, migration, invasion, and angiogenesis of MDA-MB-231 cells. An evaluation of the in vivo anti-tumor efficacy demonstrated that HTPM&AgNPs-gel showed a stronger tumor inhibition rate (68.17%) than did HTPM-gel or AgNPs-gel used alone and exhibited outstanding biocompatibility. Notably, HTPM&AgNPs-gel also inhibited lung metastasis induced by residual tumor tissue after surgery and further blocked angiogenesis-related inflammatory responses. Taken together, the suppression of inflammation by interdicting the blood vessels adjoining the tumor and inhibiting angiogenesis is a potential strategy to attenuate the recurrence and metastasis of TNBC. HTPM&AgNPs-gel is a promising anticancer agent for TNBC as a local postoperative treatment.

Strong and Thermo-Switchable Gel Adhesion Based on UCST-Type Phase Transition in Deep Eutectic Solvent.

It remains a great challenge to achieve strong and reversible hydrogel adhesion. Hydrogel adhesives also suffer from poor environmental stability due to dehydration. To overcome these problems, here reversible adhesive gels are designed using a new switching mechanism and new solvent. For the first time, the study observes UCST (upper critical solution temperature)-type thermosensitive behaviors of poly(benzyl acrylate) (PBnA) polymer and gel in menthol:thymol deep eutectic solvents (DESs). The temperature-induced phase transition allows adjusting cohesive force, and hence adhesion strength of PBnA gels by temperature. To further improve the mechanical and adhesion properties, a peptide crosslinker is used to allow energy dissipation when deforming. The resulting eutectogel exhibits thermal reversible adhesion with a high switching ratio of 14.0. The adhesion strength at attachment state reaches 0.627 MPa, which is much higher than most reversible adhesive hydrogels reported before. The low vapor pressure of DES endows the gel excellent environmental stability. More importantly, the gel can be repeatedly switched between attachment and detachment states. The strong and reversible gel adhesive is successfully used to design soft gripper for the transport of heavy cargos and climbing robot capable of moving on vertical and inverted surface in a manner similar to gecko.

Cabazitaxel-Loaded Thermosensitive Hydrogel System for Suppressed Orthotopic Colorectal Cancer and Liver Metastasis.

The treatment of colorectal cancer is always a major challenge in the field of cancer research. The number of estimated new cases of colorectal cancer worldwide in 2020 is 1 148 515, and the estimated number of deaths is 576 858, revealing that mortality accounted for approximately half of the disease incidence. The development of new drugs and strategies for colorectal cancer treatment is urgently needed. Thermosensitive injectable hydrogel PDLLA-PEG-PDLLA (PLEL) loaded with cabazitaxel (CTX) is used to explore its anti-tumor effect on mice with orthotopic colorectal cancer. CTX/PLEL is characterized by a solution state at room temperature and a hydrogel state at physiologic temperature. The excipients MPEG-PCL and PDLLA-PEG-PDLLA have good biocompatibility and biodegradability. The simple material synthesis and preparation process renders this system cost-effective and more conducive to clinical transformation. An orthotopic colorectal cancer model is established by transplantation subcutaneous tumors onto the cecum of mice. According to the results of experiments in vivo, CTX/PLEL significantly inhibits orthotopic colorectal cancer and liver metastasis in mice. The results indicate that CTX/PLEL nanoparticle preparations have high security and excellent anti-tumor effects, and have great application potential in colorectal cancer therapy.

The Method of Direct and Reverse Phase Portraits as a Tool for Systematizing the Results of Studies of Phase Transitions in Solutions of Thermosensitive Polymers.

It is shown that a more than significant amount of experimental data obtained in the field of studying systems based on thermosensitive hydrophilic polymers and reflected in the literature over the past decades makes the issue of their systematization and classification relevant. This, in turn, makes relevant the question of choosing the appropriate classification criteria. It is shown that the basic classification feature can be the number of phase transition stages, which can vary from one to four or more depending on the nature of the temperature-sensitive system. In this work, the method of inverse phase portraits is proposed for the first time. It was intended, among other things, to identify the number of phase transition stages. Moreover, the accuracy of this method significantly exceeds the accuracy of the previously used method of direct phase portraits since, for the first time, the operation of numerical differentiation is replaced by the operation of numerical integration. A specific example of the application of the proposed method for the analysis of a previously studied temperature-sensitive system is presented. It is shown that this method also allows for a quantitative comparison between the results obtained by the differential calorimetry method and the turbidimetry method. Issues related to increasing the resolution of the method of direct phase portraits are discussed.

Intra-articular hydrogel formulation prolongs the in vivo stability of Toll-like receptor antagonistic peptides for rheumatoid arthritis treatment.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic inflammation that primarily affects joint tissue and requires frequent medication. Recently, we developed cyclic phage-display-derived inhibitory peptides (CPs), which act as Toll-like Receptor 4 antagonists. These CPs exhibited therapeutic efficacy against joint diseases by alleviating inflammatory factors. Nonetheless, CP exhibits in vivo instability and a short half-life. Therefore, this study sought to improve the in vivo stability of CP, thereby reducing the frequency of CP administration through the development of an injectable hydrogel depot formulation. To improve in vivo stability, CP was chemically conjugated to hyaluronic acid (HA-CP) and subsequently mixed into a temperature-sensitive hydrogel [methoxy polyethylene glycol-b-poly(ε-caprolactone)-ran-poly(lactide) (PC)] as an injectable depot (PC+(HA-CP)). For comparison, CP was physically mixed with HA and PC (PC+(HA+CP)). Both PC+(HA-CP) and PC+(HA+CP) were found to rapidly form depots upon injection into the joint space. Cell viability assays confirmed the non-toxic nature of PC+(HA-CP) and PC+(HA+CP), whereas both formulations exhibited inhibition of inflammatory factors. Furthermore, PC+(HA-CP) retained CP for a longer duration compared to PC+(HA+CP) in the presence of hyaluronidase and within the RA joint space. Following intra-articular injection, both the PC+(HA-CP) and PC+(HA+CP) depots exhibited reductions in RA symptoms, cartilage regeneration, and suppression of pro-inflammatory cytokine levels. Specifically, by extending the in vivo retention of CP, PC+(HA-CP) demonstrated superior RA treatment efficacy compared to PC+(HA+CP). In conclusion, intra-articular injection of PC+(HA-CP) was validated as an effective strategy for treating RA, owing to its ability to prolong the in vivo retention of CP. This approach holds promise for improving RA management and patient outcomes.

Synthesis of New Glycine-Based Polymers and their Thermoresponsive Behavior in Water.

In this work, new glycine-derived polymers are developed that exhibit thermoresponsive properties in water. Therefore, a series of monomers containing one, two, or three amide functional groups and one terminal cyanomethyl group is synthesized. The resulting homopolymers, obtained by free radical polymerization (FRP) and reversible addition fragmentation chain transfer (RAFT) polymerization, display a sharp and reversible upper critical solution temperature (UCST)-type phase transition in water. Additionally, it is shown that the cloud point (TCP) can be adjusted over more than 60 °C by the number of glycyl groups present in the monomer structure and by the polymer's molar mass. These novel thermoresponsive polymers based on cyanomethylglycinamide enrich the range of nonionic UCST polymers and are promising to find applications in various fields.

Lactoferrin-Chitosan Composite Hydrogels Induced by Microbial Transglutaminase: Potential Delivery Systems for Thermosensitive Bioactive Substances.

In this work, lactoferrin (LF)-chitosan (CS) composite hydrogels with good loading capacity of thermosensitive bioactive substances were successfully obtained by microbial transglutaminase (MTG)-induced cross-linking. We evaluated the rheological, textural, and microstructural characteristics of the composite hydrogels under different conditions. The results demonstrated that the concentrations of LF and CS as well as the amount of MTG could regulate the textural properties, rheological properties, and water holding capability. The results of FTIR and fluorescence spectroscopy indicated that the main interactions within the composite gel were hydrogen and isopeptide bonds. Additionally, in vitro digestion simulation results verified that riboflavin kept stable in stomach due to the protection of LF-CS composite hydrogels and was released in small intestine. These results suggested that thermosensitive bioactive substance could be encapsulated and delivered by the LF-CS composite hydrogel, which could be applied in lots of potential applications in functional food as a new material.