Thermosensitive Chitosan Hydrogel Research Articles

Injectable Chitosan Hydrogels Doped with 2D Peptide Nanosheet-Drug Conjugates for Glutathione-Responsive Sustained Drug Delivery.

The development of novel and effective drug delivery systems aimed at enhancing therapeutic profile and efficacy of therapeutic agents is a critical challenge in modern medicine. This study presents an intelligent drug delivery system based on self-assembled two-dimensional peptide nanosheets (2D PNSs). Leveraging the tunable properties of amino acid structures and sequences, we design a peptide with the sequence of Fmoc-FKKGSHC, which self-assembles into 2D PNSs with uniform structure, high biocompatibility, and excellent degradability. Covalent attachment of thiol-modified doxorubicin (DOX) drugs to 2D PNSs via disulfide bond results in the peptide-drug conjugates (PDCs), which is denoted as PNS-SS-DOX. Subsequently, the PDCs are encapsulated within the injectable, thermosensitive chitosan (CS) hydrogels for drug delivery. The designed drug delivery system demonstrates outstanding pH-responsiveness and sustained drug release capabilities, which are facilitated by the characteristics of the CS hydrogels. Meanwhile, the covalently linked disulfide bond within the PNS-SS-DOX is responsive to intracellular glutathione (GSH) within tumor cells, enabling controlled drug release and significantly inhibiting the cancer cell growth. This responsive peptide-drug conjugate based on a 2D peptide nanoplatform paves the way for the development of smart drug delivery systems and has bright prospects in the future biomedicine field.

Functionalized chitosan hydrogel promotes osseointegration at the interface of3D printed titanium alloy scaffolds

Autogenous bone transplantation is a prevalent clinical method for addressing bone defects. However, the limited availability of donor bone and the morbidity associated with bone harvesting have propelled the search for suitable bone substitutes. Bio-inspired scaffolds, particularly those fabricated using electron beam melting (EBM) deposition technology, have emerged as a significant advancement in this field. These 3D-printed titanium alloy scaffolds are celebrated for their outstanding biocompatibility and favorable elastic modulus. Thermosensitive chitosan hydrogel, which transitions from liquid to solid at body temperature, serves as a popular carrier in bone tissue engineering. Icariin (ICA), known for its efficacy in promoting osteoblast differentiation from bone marrow mesenchymal stem cells (BMSCs), plays a crucial role in this context. We developed a system combining a 3D-printed titanium alloy with a thermosensitive chitosan hydrogel, capable of local bone regeneration and integration through ICA delivery. Our in vitro findings reveal that this system can gradually release ICA, demonstrating excellent biocompatibility while fostering BMSC proliferation and osteogenic differentiation. Immunohistochemistry and Micro-CT analyses further confirm the effectiveness of the system in accelerating in vivo bone regeneration and enhancing osseointegration. This composite system lays a significant theoretical foundation for advancing local bone regeneration and integration.

Chitosan thermogelation and cascade mineralization via sequential CaCO3 incorporations for wound care

Physically crosslinked hydrogels have shown great potential as excellent and eco-friendly matrices for wound management. Herein, we demonstrate the development of a thermosensitive chitosan hydrogel system using CaCO3 as a gelling agent, followed by CaCO3 mineralization to fine-tune its properties. The chitosan hydrogel effectively gelled at 37 °C and above after an incubation period of at least 2 h, facilitated by the CaCO3-mediated slow deprotonation of primary amine groups on chitosan polymers. Through synthesizing and characterizing various chitosan hydrogel compositions, we found that mineralization played a key role in enhancing the hydrogels' mechanical strength, viscosity, and thermal inertia. Moreover, thorough in vitro and in vivo assessments of the chitosan-based hydrogels, whether modified with mineralization or not, demonstrated their outstanding hemostatic activity (reducing coagulation time by >41 %), biocompatibility with minimal inflammation, and biodegradability. Importantly, in vivo evaluations using a rat burn wound model unveiled a clear wound healing promotion property of the chitosan hydrogels, and the mineralized form outperformed its precursor, with a reduction of >7 days in wound closure time. This study presents the first-time utilization of chitosan/CaCO3 as a thermogelation formulation, offering a promising prototype for a new family of thermosensitive hydrogels highly suited for wound care applications.

Artesunate-loaded thermosensitive chitosan hydrogel promotes osteogenesis of maxillary tooth extraction through regulating T lymphocytes in type 2 diabetic rats.

Type 2 diabetes mellitus (T2DM) causes severe bone loss after tooth extraction as a hyperglycemic environment causes aberrant bone homeostasis. Artesunate (ART) is known to possess anti-inflammation and osteogenic properties. However, its osteogenesis property in alveolar bone remains unclear. This study aimed to explore the osteogenic and immunoregulatory effects of artesunate-loaded thermosensitive chitosan hydrogel (ART-loaded TCH) on maxilla tooth extraction in T2DM rats. T2DM rats were induced by a high-fat diet and streptozotocin. Different concentrations of ART-loaded TCH were applied in tooth extraction sockets. Bone loss and the expression of osteogenic regulatory factors (OPG, ALP, RANK) were evaluated. The immunoregulatory effects of ART-loaded TCH were observed through detecting the infiltration of T lymphocytes and their cytokines. The underlying mechanisms were explored. Results showed that the 150mg/ml ART-loaded TCH group significantly ameliorated maxilla bone height and bone mineral density when compared with the T2DM group (p < 0.05). It also improved the expression of OPG, ALP, and RANK. Although the alteration of CD4+ T, CD8+ T, and CD4+:CD8+ T ratio has no significant difference among groups, the release of Th1 and Th2 in the 150mg/ml ART-loaded TCH group has been significantly regulated than in the T2DM group (p < 0.05). Besides, ART-loaded TCH treatment inhibited the expression of p38 MAPK and ERK1 in T2DM maxilla. Therefore, the results indicated that 150mg/ml ART-loaded TCH could be an effective method to prevent bone loss in T2DM tooth extraction rats by modulating the immunoregulation of Th1 and Th2 and the MAPK signaling pathway.

Research on triamcinolone-loaded thermosensitive chitosan hydrogels for preventing esophageal stricture induced by endoscopic submucosal dissection

Early-stage esophageal cancer is primarily treated by endoscopic submucosal dissection (ESD). However, extensive mucosal dissection creates a significant risk of postoperative esophageal stricture. Clinically, postoperative stricture can be prevented by glucocorticoids; however, there are drawbacks to both systemic and local administration of glucocorticoids, and improving drug administration methods is crucial. In this study, we developed a chitosan-based thermosensitive hydrogel for triamcinolone (TA) delivery. Our results indicated that the hydrogel remains liquid at low temperatures and can be injected into the esophageal wound site through an endoscopic biopsy channel. Upon reaching body temperature, the hydrogel undergoes spontaneous gelation and firmly adheres to the wound surface. The liquid phase enables convenient and precise delivery, while the gel phase achieves remarkable adhesion, tensile strength, and resistance to degradation. Moreover, the hydrogel exhibited an extended release duration of >10 days when loaded with a 10 mg dose. In vitro studies revealed that the hydrogel suppresses the proliferation and fibrogenesis of human scar fibroblasts (HKF). In a rat skin dermal defect model, the hydrogel attenuated keloid formation during the healing process. Consequently, the chitosan-based thermosensitive hydrogel developed in this study for triamcinolone delivery may be an effective tool for preventing post-ESD esophageal stricture.

Thermosensitive Chitosan Hydrogels: A Potential Strategy for Prolonged Iron Dextran Parenteral Supplementation.

Iron deficiency anemia (IDA) presents a global health challenge, impacting crucial development stages in humans and other mammals. Pigs, having physiological and metabolic similarities with humans, are a valuable model for studying and preventing anemia. Commonly, a commercial iron dextran formulation (CIDF) with iron dextran particles (IDPs) is intramuscularly administered for IDA prevention in pigs, yet its rapid metabolism limits preventive efficacy. This study aimed to develop and evaluate chitosan thermosensitive hydrogels (CTHs) as a novel parenteral iron supplementation strategy, promoting IDPs' prolonged release and mitigating their rapid metabolism. These CTHs, loaded with IDPs (0.1, 0.2, and 0.4 g of theoretical iron/g of chitosan), were characterized for IM iron supplementation. Exhibiting thermosensitivity, these formulations facilitated IM injection at ~4 °C, and its significant increasing viscosity at 25-37 °C physically entrapped the IDPs within the chitosan's hydrophobic gel without chemical bonding. In vitro studies showed CIDF released all the iron in 6 h, while CTH0.4 had a 40% release in 72 h, mainly through Fickian diffusion. The controlled release of CTHs was attributed to the physical entrapment of IDPs within the CTHs' gel, which acts as a diffusion barrier. CTHs would be an effective hydrogel prototype for prolonged-release parenteral iron supplementation.

β-Tricalcium Phosphate-Loaded Chitosan-Based Thermosensitive Hydrogel for Periodontal Regeneration.

The current treatment for periodontitis is aimed at resolving gingival inflammation, whilst complete periodontal tissue regeneration is not predictable, and it represents a therapeutic challenge. Injectable biomaterials hold tremendous potential in dental tissue regeneration. This study aimed to investigate the ability of an injectable thermosensitive β-tricalcium phosphate (β-TCP) and chitosan-based hydrogel to carry cells and promote periodontal tissue regeneration. In this study, different concentrations of β-TCP-loaded chitosan hydrogels were prepared (0%, 2%, 4%, or 6% β-TCP, 10% β-glycerol phosphate, and 1.5% chitosan). The characteristics of the hydrogels were tested using rheology, a scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), degradation, and biological analyses. The new biomaterial showed a sol-gel transformation ability at body temperature and exhibited excellent chemical and physical characteristics, whilst the existence of β-TCP enhanced the structure and the properties of the hydrogels. The SEM confirmed the three-dimensional networks of the hydrogels, and the typical rheological properties of strong gel were observed. The EDX and XRD validated the successful incorporation of β-TCP, and similar patterns between different groups were found in terms of the FTIR spectra. The stable structure of the hydrogels under 100 °C was confirmed via DSC. Biological tests such as Alamar Blue assay and Live/Dead staining confirmed the remarkable biocompatibility of the hydrogels with pre-osteoblast MC3T3-E1 and human gingival fibroblast (HGF) cells for 14 days, and the results were validated with confocal imaging. This preliminary study shows great promise for the application of the β-TCP-loaded thermosensitive chitosan hydrogels as a scaffold in periodontal bone and soft tissue repair.

Thermosensitive black phosphorus hydrogel loaded with silver sulfadiazine promotes skin wound healing

Wounds can lead to skin and soft tissue damage and their improper management may lead to the growth of pathogenic bacteria at the site of injury. Identifying better ways to promote wound healing is a major unmet need and biomedical materials with the ability to promote wound healing are urgently needed. Here, we report a thermosensitive black phosphorus hydrogel composed of black phosphorus nano-loaded drug silver sulfadiazine (SSD) and chitosan thermosensitive hydrogel for wound healing. The hydrogel has temperature-sensitive properties and enables the continuous release of SSD under near-infrared irradiation to achieve synergistic photothermal and antibacterial treatment. Additionally, it exerts antibacterial effects on Staphylococcus aureus. In a rat skin injury model, it promotes collagen deposition, boosts neovascularization, and suppresses inflammatory markers. In summary, the excellent thermosensitivity, biocompatibility, and wound-healing-promoting qualities of the reported thermosensitive hydrogel make it suitable as an ideal wound dressing in the clinic.

Encapsulation of Triphasia trifolia extracts by pH and thermal dual-sensitive chitosan hydrogels for controlled release

Recent studies have developed varied delivery systems incorporating natural compounds to improve the limitations of plant extracts for clinical use while enabling their controlled release at treatment sites. For the first time, ethanolic limeberry extract (Triphasia trifolia) has been successfully encapsulated in thermo-sensitive chitosan hydrogels by a facile in situ loading. The extract-incorporated chitosan hydrogels have a pH value of nearly 7.00, gelation temperatures in the range of 37–38 °C, and exhibit an open-cell porous structure, thus allowing them to absorb and retain 756 % of their mass in water. The in vitro extract release from the hydrogels is driven by both temperature and pH, resulting in more than 70 % of the initial extract being released within the first 24 h. Although the release half-life of hydrogels at pH 7.4 is longer, their release capacity is higher than that at pH 6.5. Upon a 2 °C increase in temperature, the time to release 50 % initial extract is sharply reduced by 20–40 %. The release kinetics from the hydrogels mathematically demonstrated that diffusion is a prominent driving force over chitosan relaxation. Consequently, the developed hydrogels encapsulating the limeberry extract show their heat and pH sensitivity in controlled release for treating chronic wounds.

Chitosan Thermosensitive Hydrogel Based on DNA Damage Repair Inhibition and Mild Photothermal Therapy for Enhanced Antitumor Treatment.

The DNA damage repair of tumor cells limits the effect of photothermal therapy (PTT), and high temperatures induced by PTT can damage adjacent normal tissues. To overcome these limitations, we developed a novel composite hydrogel (OLA-Au-Gel) based on chitosan (CS) and β-glycerophosphate (β-GP), which encapsulated olaparib-liposomes (OLA-lips) and CS-capped gold nanoparticles (CS-AuNPs). OLA-Au-Gel achieved the combination of mild PTT (mPTT) by CS-AuNPs and tumor DNA damage repair inhibition by OLA. The hydrogel showed good biocompatibility, injectability, and photothermal response. Under near-infrared laser irradiation, OLA-Au-Gel inhibited the proliferation of tumor cells, induced the generation of reactive oxygen species in vitro, and effectively inhibited the growth of breast tumors in vivo. OLA-Au-Gel shows a promising application prospect for inhibiting tumor development and improving the antitumor effect. Collectively, we propose a novel strategy for enhanced antitumor therapy based on the combination of mPTT and DNA damage repair inhibition.

Poly(N-isopropyacrylamide-co-maleic acid )/acylated chitosan thermosensitive hydrogels: preparation and properties

Poly(N-isopropyacrylamide-co-maleic acid )/acylated chitosan thermosensitive hydrogels: preparation and properties

Nanosonosensitizers-engineered injectable thermogel for augmented chemo-sonodynamic therapy of melanoma and infected wound healing.

Easy recurrence and bacteria infected-wound healing after surgery excision pose severe challenges to clinical melanoma therapy. Herein, an injectable CuO2 nanodots-engineered thermosensitive chitosan hydrogel (CuO2-BSO@Gel) for enhanced melanoma chemo-sonodynamic therapy and improved infected wound healing was rationally constructed by facilely integrating the CuO2 nanodots and L-Buthionine-(S, R)-sulfoximine (BSO) with thermoresponsive hydrogel. Favored by the Fenton catalytic activity of Cu2+, the CuO2 nanodots can achieve enhanced chemodynamic therapy (CDT) by self-supplying H2O2 under acidic tumor microenvironment. Simultaneously, the CuO2 nanodots with a narrow bandgap (2.29​eV) were proven to be the efficient sonosensitizers, and the corresponding quantum yield of singlet oxygen (1O2) could be boosted by the O2 generation during Fenton-like reactions. Additionally, combining with the glutathione (GSH) depletion of loaded BSO, intracellular oxidative stress induced by SDT and CDT was further amplified, leading to the specific ferroptosis. Importantly, this multifunctional hydrogel significantly promoted the proliferation of normal skin cells and accelerated the bacteria-infected wound healing by the effective chemo-sonodynamic antibacterial activity and the enhanced angiogenesis. Thus, the engineered thermogel features the distinct chemo-sonodynamic performance, desirable biocompatibility and bioactivity, providing a competitive strategy for eradicating melanoma and infected wound healing.

THERMOSENSITIVE HYDROGEL LOADED WITH ENGINEERED ADIPOSE STEM CELLS FOR THE TREATMENT OF DEGENERATIVE INTERVERTEBRAL DISC

Intervertebral disc degeneration can lead to physical disability and significant pain, while the present therapeutics still fail to biochemically and biomechanically restore the tissue. Stem cell-based therapy in treating intervertebral disc (IVD) degeneration is promising while transplanting cells alone might not be adequate for effective regeneration. Recently, gene modification and 3D-printing strategies represent promising strategies to enhanced therapeutic efficacy of MSC therapy. In this regard, we hypothesized that the combination of thermosensitive chitosan hydrogel and adipose derived stem cells (ADSCs) engineered with modRNA encoding Interleukin − 4 (IL-4) can inhibit inflammation and promote the regeneration of the degenerative IVD.Rat ADSCs were acquired from adipose tissue and transfected with modRNAs. First, the kinetics and efficacy of modRNA-mediated gene transfer in mouse ADSCs were analyzed in vitro. Next, we applied an indirect co-culture system to analyze the pro-anabolic potential of IL-4 modRNA engineered ADSCs (named as IL-4-ADSCs) on nucleus pulposus cells.ModRNA transfected mouse ADSCs with high efficiency and the IL-4 modRNA-transfected ADSCs facilitated burst-like production of bio-functional IL-4 protein. In vitro, IL-4-ADSCs induced increased anabolic markers expression of nucleus pulposus cells in inflammation environment compared to untreated ADSCs.These findings collectively supported the therapeutic potential of the combination of thermosensitive chitosan hydrogel and IL-4-ADSCs for intervertebral disc degeneration management. Histological and in vivo validation are now being conducted.

Injectable cell-laden hybrid bioactive scaffold containing bioactive glass microspheres.

The rising incidence of bone disorders has resulted in the need for minimally invasive therapies to meet this demand. Injectable bioactive filler, alone or with cells, could be applied in a minimally invasive manner to fulfill irregular cavities in non-load bearing sites, which do not require high mechanical properties. Thermosensitive chitosan hydrogels that transition from a liquid to a mechanically stable solid at body temperature provide interesting features as in-situ injectable cytocompatible biomaterials, but they are not osteoconductive. Osteoconductivity can be applied in combination with bioactive ceramics e.g., 45S5-Bioglass® (BG). However, BG addition in chitosan hydrogels results in pH elevation, due to rapid ions release, which adversely affects gel formation, mechanical properties, and cytocompatibility. To address this, we created hybrid hydrogels, where BG is concentrated in chitosan-based microbeads, incorporated in in-situ gelling chitosan hydrogels. We then compared the hybrid hydrogels' properties to chitosan hydrogels with homogenously distributed BG. By varying the stirred emulsification process, BG percentage, and CH formulation, we could tune the microbeads' properties. Incorporation of BG microbeads drastically improved the hydrogel's compressive modulus in comparison to homogeneously distributed BG. It also strongly increased the survival and metabolic activities of encapsulated cells. Calcium/phosphate increase on BG microbeads suggests hydroxyapatite formation. The small diameter of microbeads allows minimally invasive injection through small needles. The feasibility of freezing and thawing microbeads provides the possibility of long-term storage for potential clinical applications. These data indicate that this hybrid hydrogel forms a promising injectable cell-laden bioactive biomaterial for the treatment of unloaded bone defects.

Effect of P311 microspheres-loaded thermosensitive chitosan hydrogel on the wound healing of full-thickness skin defects in rats

Objective: To explore the effect of P311 microspheres-loaded thermosensitive chitosan hydrogel on the wound healing of full-thickness skin defects in rats. Methods: The method of experimental study was adopted. The polyvinyl alcohol/sodium alginate microspheres (simple microspheres), P311 microspheres, and bovine serum albumin labeled with fluorescein isothiocyanate (FITC-BSA) microspheres were prepared by water-in-oil emulsification, and then their morphology was observed under a light microscope/inverted fluorescence microscope. Chitosan solution was prepared, chitosan solution and β-glycerol phosphate disodium hydrate were mixed to prepare simple thermosensitive hydrogels, and thermosensitive hydrogels loaded with simple microspheres or P311 microspheres were prepared by adding corresponding substances in simple thermosensitive hydrogels. The morphological changes of the prepared four liquids in the state of tilt was observed at 37 ℃. After being freeze-dried, the micromorphology of the prepared four liquids was observed under a scanning electron microscope. Eighteen 3-4-week-old male Sprague-Dawley rats were divided into normal group without any treatment, dressing group, chitosan group, hydrogel alone group, simple microspheres-loaded hydrogel group, and P311 microspheres-loaded hydrogel group, which were inflicted with one full-thickness skin defect wound on both sides of the back spine and were dealt correspondingly, with 3 rats in each group. Rats with full-thickness skin defects in the five groups were collected, the wound healing was observed on post injury day (PID) 0 (immediately), 5, 10, and 15, and the wound healing rates on PID 5, 10, and 15 were calculated. The wound and wound margin tissue of rats with full-thickness skin defects in the five groups on PID 15 and normal skin tissue in the same site of rats in normal group were collected, hematoxylin and eosin staining was conducted to observe the histological changes, immunohistochemical staining was performed to observe the expressions of CD31 and vascular endothelial growth factor (VEGF), and Western blotting was conducted to detect the protein expressions of CD31 and VEGF. The number of samples was all three. Data were statistically analyzed with one-way analysis of variance, analysis of variance for repeated measurement, and Bonferroni correction. Results: Simple microspheres were spherical, with loose and porous surface. The surfaces of P311 microspheres and FITC-BSA microspheres were smooth without pores, and the FITC-BSA microspheres emitted uniform green fluorescence. The diameters of the three microspheres were basically consistent, being 33.1 to 37.7 μm. Compared with chitosan solution and simple thermosensitive hydrogel, the structures of the two microspheres-loaded hydrogels were more stable in the state of tilt at 37 ℃. The two microspheres-loaded hydrogels had denser network structures than those of chitosan solution and simple thermosensitive hydrogel, and in the cross section of which microspheres with a diameter of about 30 μm could be seen. Within PID 15, the wounds of rats in the five groups were healed to different degrees, and the wound healing of rats in P311 microspheres-loaded hydrogel group was the best. On PID 5, 10, and 15, the wound healing rates of rats in dressing group and chitosan group were (26.6±2.4)%, (38.5±3.1)%, (50.9±1.5)%, (47.6±2.0)%, (58.5±3.6)%, and (66.7±4.1)%, respectively, which were significantly lower than (59.3±4.8)%, (87.6±3.2)%, (97.2±1.0)% in P311 microspheres-loaded hydrogel group (P<0.05 or P<0.01). The wound healing rates of rats in hydrogel alone group on PID 10 and 15, and in simple microspheres-loaded hydrogel group on PID 15 were (76.0±3.3)%, (84.5±3.6)%, and (88.0±2.6)%, respectively, which were significantly lower than those in P311 microspheres-loaded hydrogel group (P<0.05). The epidermis, hair follicles, and sebaceous glands could be seen in the normal skin of rats in normal group, without positive expressions of CD31 or VEGF. The wounds of rats in P311 microspheres-loaded hydrogel group on PID 15 were almost completely epithelialized, with more blood vessels, hair follicles, sebaceous glands, and positive expressions of CD31 and VEGF in the wounds than those of rats with full-thickness skin defects in the other four groups, and more protein expressions of CD31 and VEGF than those of rats in the other five groups. Conclusions: The P311 microspheres-loaded thermosensitive chitosan hydrogel can release the encapsulated drug slowly, prolong the drug action time, and promote wound healing in rats with full-thickness skin defects by promoting wound angiogenesis and re-epithelialization.

Injectable Immunotherapeutic Hydrogel Containing RNA-Loaded Lipid Nanoparticles Reshapes Tumor Microenvironment for Pancreatic Cancer Therapy.

Pancreatic cancer immunotherapy is becoming a promising strategy for improving the survival rate of postsurgical patients. However, the low response rate to immunotherapy suggests a low number of antigen-specific T cells and a high number of immunosuppressive tumor-associated macrophages in the pancreatic tumor microenvironment. Herein, we developed an in situ injectable thermosensitive chitosan hydrogel loaded with lipid-immune regulatory factor 5 (IRF5) mRNA/C-C chemokine ligand 5 (CCL5) siRNA (LPR) nanoparticle complexes (LPR@CHG) that reprogram the antitumoral immune niche. The LPR@CHG hydrogel upregulates IRF5 and downregulates CCL5 secretion, which contribute to a significant increase in M1 phenotype macrophages. Tumor growth is controlled by effective M1 phenotype macrophage that initiate T cell-mediated immune responses. Overall, the LPR@CHG hydrogel is expected to be a meaningful immunotherapy platform that can reshape the immunosuppressive tumor microenvironment and improve the efficacy of current pancreatic immunotherapies while minimizing systemic toxicity.

Sorption of calcium by chitosan hydrogel: Kinetics and equilibrium

One of the major applications of chitosan is based on its ability to bind ions. In essence, the presence of active hydroxyl groups (-OH) and amino groups (-NH2), chitosan coordinates easily e.g. with transition metal ions, meanwhile it has a weak adsorption properties towards to alkaline earth metals. In this paper, a batch adsorption system was applied to study the adsorption of Ca(II) ions from aqueous solution by thermosensitive chitosan hydrogels. Due to the presence of sodium β-glycerophosphate (β-GP) in the sol structure, chitosan salts respond with phase transition and obtain thermosensitive properties, including changes in sorption abilities. Experimental research (the maximum adsorption capacity obtained 1.157 g g−1) and theoretical investigation on sorption of calcium in range of concentrations of CaCl2 solution, has been studied. Equilibria were described by Langmuir, Freundlich, Toth, Redlich-Peterson, Dubinin-Radushkevich, Radke-Praushnitz, Fritz-S, Langmuir-Freundlich, Marczewski-Jaroniec, Bi-Langmuir isotherm equations. Whereas, to describe sorption kinetics an original model was proposed, which combine chemical reaction on sorbent surface and intraparticle diffusion. The process of sorption was described by two parameters: diffusion coefficient DAB = 2.967·10−9 m2 s−1 and surface process rate constant kv = 9.129·10−5 s−1.

Evaluation of thermosensitive chitosan hydrogel containing gefitinib loaded cellulose acetate butyrate nanoparticles in a subcutaneous breast cancer model

In the present study, gefitinib loaded cellulose acetate butyrate nanoparticles (Gnb-NPs) were prepared and then incorporated into thermo-sensitive chitosan/β-glycerophosphate hydrogels for intratumoral administration in mice bearing breast cancer. Accordingly, Gnb-NPs were prepared using the solvent evaporation process and optimized by applying a two-level fractional factorial design. Properties of NPs, including particle size, zeta potential (ZP), polydispersity index (PdI), encapsulation efficiency (EE) % and drug loading (DL) %, were investigated; the optimized Gnb-NPs were then loaded in chitosan hydrogels (Gnb-NPs-Hydrogel). The formulated Gnb-NPs-Hydrogel was assessed in terms of gelling time, release behavior, injectability, swelling and degradation behavior. The anti-cancer efficacy of Gnb-NPs-Hydrogel was evaluated in vitro against the 4 T1 breast cancer cell line and in vivo in breast tumor bearing mice. The optimized formulation showed spherical particles with the size of 156.50 ± 2.40 nm, PdI of 0.20 ± 0.002, ZP of −4.90 ± 0.04 mV, EE of 99.77 ± 0.09 % and DL of 20.59 ± 0.05 %. Incorporating Gnb-NPs into the hydrogel led to the decrease of the drug release rate. Gnb-NPs-Hydrogel displayed a greater cytotoxic effect in comparison to the free Gnb and Gnb-Hydrogel in 4 T1 cancer cells. Furthermore,intratumorallyinjectedGnb-NPs-Hydrogel showed the strongest antitumor efficacy in vivo. The superior performance of Gnb-NPs-Hydrogel, thus, demonstrated its potential for the treatment of breast cancer.

Controlled Liposome Delivery from Chitosan-Based Thermosensitive Hydrogel for Regenerative Medicine.

This work describes the development of an injectable nanocomposite system based on a chitosan thermosensitive hydrogel combined with liposomes for regenerative medicine applications. Liposomes with good physicochemical properties are prepared and embedded within the chitosan network. The resulting nanocomposite hydrogel is able to provide a controlled release of the content from liposomes, which are able to interact with cells and be internalized. The cellular uptake is enhanced by the presence of a chitosan coating, and cells incubated with liposomes embedded within thermosensitive hydrogels displayed a higher cell uptake compared to cells incubated with liposomes alone. Furthermore, the gelation temperature of the system resulted to be equal to 32.6 °C; thus, the system can be easily injected in the target site to form a hydrogel at physiological temperature. Given the peculiar performance of the selected systems, the resulting thermosensitive hydrogels are a versatile platform and display potential applications as controlled delivery systems of liposomes for tissue regeneration.

A hybrid oxygen-generating wound dressing based on chitosan thermosensitive hydrogel and decellularized amniotic membrane

Amniotic membrane (AM) has been utilized as a wound dressing extensively. Given the importance of oxygen in wound healing, here we have reported the fabrication and characterization of an oxygen-generating wound dressing based on AM. This construct was composed of H2O2-loaded polylactic acid (PLA) microparticles embedded within a chitosan/β-glycerophosphate (β-GP) thermosensitive hydrogel covered with a layer of decellularized human-AM. The microparticles had a diameter of 4.48 ± 1.8 μm, an encapsulation efficiency of 44.172 ± 4.49%, and generated oxygen for at least 7 days. The hybrid construct was formed at 32.4 ± 2 °C, had a porous structure (84.69 ± 8.34%) with a pore size of 46.72 ± 26.21 μm. The hydrogel/dAM extract was non-toxic after 7 days based on our MTT results, and the final composite supported cell growth and adhesion. This sample had the most negligible blood cell adhesion with less than 5% hemolysis. Our results indicate the proposed structure's desirable biological, chemical, and physical properties as an active wound dressing.