Sequential-Crosslinking Fibrin Glue for Rapid and Reinforced Hemostasis.

Achieving hemostasis effectively is essential for surgical success and excellent patient outcomes. However, it is challenging to develop hemostatic adhesives that are fast-acting, strongly adherent, long-lasting, and biocompatible for treating hemorrhage. In this study, a sequential crosslinking fibrin glue (SCFG) is developed, of which the first network of the fibrin glue forms in situ within 2 s to act as an initial physical barrier and locks the gelatin methacryloyl precursor for tight construction of the second network to enhance wet adhesion and durability for tissues covered with blood. The sequential crosslinking glue can provide large pressures (≈280 mmHg of burst pressure), makes strong (38 kPa of shear strength) and tough (≈60 J m-2 of interfacial toughness) interfaces with wet tissues, and outperforms commercial hemostatic agents and gelatin methacryloyl. SCFG are demonstrated as an effective and safe sealant to enhance the treatment outcomes of bleeding tissues in rat, rabbit, and pig models. The ultrafast gelation, strong adhesion and durability, excellent compatibility, and easy manufacture of SCFG make it a promising hemostatic adhesive for clinical applications.

Engineering Clinically Relevant Probiotics with Switchable "Nano-Promoter" and "Nano-Effector" for Precision Tumor Therapy.

Probiotics have the potential as biotherapeutic agents for cancer management in preclinical models and human trials by secreting antineoplastic or immunoregulatory agents in the tumor microenvironment (TME). However, current probiotics lack the ability to dynamically respond to unique TME characteristics, leading to limited therapeutic accuracy and efficacy. Although progress has been made in customizing controllable probiotics through synthetic biology, the engineering process is complex and the predictability of production is relatively low. To address this, here, for the first time, this work adopts pH-dependent peroxidase-like (POD-like) artificial enzymes as both an inducible "nano-promoter" and "nano-effector" to engineer clinically relevant probiotics to achieve switchable control of probiotic therapy. The nanozyme initially serves as an inducible "nano-promoter," generating trace amounts of nonlethal reactive oxygen species (ROS) stress to upregulate acidic metabolites in probiotics. Once metabolites acidify the TME to a threshold, the nanozyme switches to a "nano-effector," producing a great deal of lethal ROS to fight cancer. This approach shows promise in subcutaneous, orthotopic, and colitis-associated colorectal cancer tumors, offering a new methodology for modulating probiotic metabolism in a pathological environment.

Artificial-enzymes-armed Bifidobacterium longum probiotics for alleviating intestinal inflammation and microbiota dysbiosis.

Inflammatory bowel disease can be caused by the dysfunction of the intestinal mucosal barrier and dysregulation of gut microbiota. Traditional treatments use drugs to manage inflammation with possible probiotic therapy as an adjuvant. However, current standard practices often suffer from metabolic instability, limited targeting and result in unsatisfactory therapeutic outcomes. Here we report on artificial-enzyme-modified Bifidobacterium longum probiotics for reshaping a healthy immune system in inflammatory bowel disease. Probiotics can promote the targeting and retention of the biocompatible artificial enzymes to persistently scavenge elevated reactive oxygen species and alleviate inflammatory factors. The reduced inflammation caused by artificial enzymes improves bacterial viability to rapidly reshape the intestinal barrier functions and restore the gut microbiota. The therapeutic effects are demonstrated in murine and canine models and show superior outcomes to traditional clinical drugs.

pH-responsive hybrid platelet membrane-coated nanobomb with deep tumor penetration ability and enhanced cancer thermal/chemodynamic therapy.

Background: Despite their outstanding properties in high surface-to-volume ratio and deep penetration, the application of ultrasmall nanoparticles for tumor theranostics remains limited because of their dissatisfied targeting performance and short blood circulation lifetime. Various synthetic materials with complex structures have been prepared as a multifunctional platform for loading ultrasmall nanoparticles. However, their use in nanomedicine is restricted because of unknown metabolic processes and potential physiological toxicity. Therefore, versatile and biocompatible nanoplatforms need to be designed through a simple yet effective method for realizing specific delivery and responsible release of ultrasmall nanoparticles. Methods: Iron-gallic acid coordination polymer nanodots (FeCNDs) exhibits outstanding photothermal ability and Fenton catalytic performance, which can be applied for tumor inhibition via hyperthermia and reactive oxygen species. A pH-responsive platelet-based hybrid membrane (pH-HCM) was prepared via co-extrusion and acted as a safe nanoplatform to load FeCNDs (pH-HCM@FeCNDs). Subsequently, their responsive performance and penetration ability were valued considering the multicellular sphere (MCS) model in an acidic or neutral environment. Thereafter, in vivo fluorescence image was performed to assess targeting capability of pH-HCM@FeCNDs. Finally, the corresponding antitumor and antimetastatic effects on orthotropic breast cancer were investigated. Results: In 4T1 MCS model, pH-HCM@FeCNDs group exhibited higher penetration efficiency (72.84%) than its non-responsive counterparts (17.77%) under an acidic environment. Moreover, the fluorescence intensity in pH-HCM@FeCNDs group was 3.18 times higher than that in group without targeting performance in the in vivo fluorescence image experiment. Finally, through in vivo experiments, pH-HCM@FeCNDs was confirmed to exhibit the best antitumor effect (90.33% tumor reduction) and antimetastatic effects (only 0.29% tumor coverage) on orthotropic breast cancer. Conclusions: Hybrid cell membrane was an ideal nanoplatform to deliver nanodots because of its good responsibility, satisfactory targeting ability, and excellent biocompatibility. Consequently, this study provides novel insights into the delivery and release of nanodots in a simple but effect method.

Preclinical validation of silibinin/albumin nanoparticles as an applicable system against acute liver injury.

BACKGROUND: Silibinin (SIL) has been extensively studied for its therapeutic effects on various liver diseases. However, its effect on acute liver injury was limited for poor solubility and low bioavailability. Thus, we prepared SIL and bovine serum albumin (SIL/BSA) nanoparticles and further evaluated their therapeutic efficacy against acute liver injury in mouse models. METHODS: SIL/BSA nanoparticles were prepared via a nanoprecipitation method. Both in vitro cell culture model and in vivo mouse models of acetaminophen (APAP) and lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury were used to evaluate the therapeutic effect of SIL/BSA nanoparticles and potential mechanisms. RESULTS: The SIL/BSA nanoparticles with hydrophilic diameters of 90 ± 29 nm were stably suspended. SIL/BSA nanoparticles presented better biocompatibility and more liver distribution in vivo than SIL microparticles. SIL/BSA nanoparticles significantly alleviated APAP and LPS/D-GalN induced acute liver injury in mice. Similarly, SIL/BSA nanoparticles remarkably enhanced the viability of hepatocytes in vitro against both APAP and LPS/D-GalN induced hepatocyte damage. Moreover, SIL/BSA nanoparticles exhibited antioxidant effects against intracellular oxidative stress via upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway, decreasing ROS and regulating antioxidant enzyme reactivity. And the downstream of mitochondria damage and caspase 9/3 related apoptosis pathway was also inhibited CONCLUSION: SIL/BSA nanoparticles were successfully prepared to enhance the liver availability of SIL. Both in vivo and in vitro, SIL/BSA nanoparticles exerted ideal hepatoprotective and antioxidant efficacy against acute liver injury, suggesting the promising future in clinical transfer. STATEMENT OF SIGNIFICANCE: In our study, we prepared small-size, stable and well-dispersed silibinin/bovine serum albumin (SIL/BSA) nanoparticles via using simple and cost-effective nanoprecipitation techniques. Their physicochemical and pharmacokinetic characteristics were analyzed. We systematically studied the hepatoprotective and antioxidant efficacy of SIL/BSA both in vivo and in vitro, using two acute liver injury models. These findings revealed that SIL/BSA nanoparticles exerted ideal hepatoprotective and antioxidant efficacy against acute liver injury, suggesting the promising future in clinical transfer.

Thin film nanoarchitectonics of layer-by-layer assembly with reduced graphene oxide on intraocular lens for photothermal therapy of posterior capsular opacification.

Due to development of surgical techniques and intraocular lens (IOL) implants, vision can often be restored in cataracts patients. However, posterior capsular opacification (PCO) has become the most common and challenging complication in cataracts surgery. While various approaches such as surface modification and drug prophylaxis have been investigated to prevent PCO development, there is no standard treatment that is sufficiently safe and effective to meet clinical demands. Near-infrared (NIR) light-triggered photothermal therapy is an attractive noninvasive treatment for PCO prophylaxis. We fabricated a new type of IOL with excellent biocompatibility, stability, and photothermal conversion property. Polyethyleneimine (PEI) and graphene oxide (GO) were layer-by-layer assembled on model polymethylmethacrylate and IOL substrates, and the thickness, surface roughness, and wettability of the substrates with different numbers of bilayers were evaluated. After the reduction of GO to reduced GO (rGO), a rGO/PEI multilayer thin film with good stability and photothermal conversion capability was obtained. The rGO/PEI multilayer coating was able to induce apoptosis in lens epithelium cells under 808-nm NIR laser irradiation in vitro. Finally, rGO@IOL was implanted into rabbit eyes, and the biocompatibility and ability to prevent PCO were evaluated for 5 weeks. The rGO@IOL implant exhibited excellent PCO prevention ability with the assistance of NIR irradiation and did not induce obvious pathological effects in surrounding healthy tissues. The rGO@IOL implant with good biocompatibility, good physicochemical stability, and excellent photothermal conversion property shows promise for clinical application in PCO prophylaxis.

An NIR Discrete Metallacycle Constructed from Perylene Bisimide and Tetraphenylethylene Fluorophores for Imaging-Guided Cancer Radio-Chemotherapy.

To promote the clinical theranostic performances of platinum-based anticancer drugs, imaging capability is urgently desired, and their chemotherapeutic efficacy needs to be upgraded. Herein, a theranostic metallacycle (M) is developed for imaging-guided cancer radio-chemotherapy using perylene bisimide fluorophore (PPy) and tetraphenylethylene-based di-Pt(II) organometallic precursor (TPE-Pt) as building blocks. The formation of this discrete supramolecular coordination complex facilitates the encapsulation of M by a glutathione (GSH)-responsive amphiphilic block copolymer to prepare M-loaded nanoparticles (MNPs). TPE-Pt acts as a chemotherapeutic drug and also an excellent radiosensitizer, thus incorporating radiotherapy into the nanomedicine to accelerate the therapeutic efficacy and overcome drug resistance. The NIR-emission of PPy is employed to detect the intracellular delivery and tissue distribution of MNPs in real time. In vitro and in vivo investigations demonstrate the excellent anticancer efficacy combining chemotherapy and radiotherapy; the administration of this nanomedicine effectively inhibits the tumor growth and greatly extends the survival rate of cisplatin-resistant A2780CIS-tumor-bearing mice. Guided by in vivo fluorescence imaging, radio-chemotherapy is precisely carried out, which facilitates boosting of the therapeutic outcomes and minimizing undesired side effects. The success of this theranostic system brings new hope to supramolecular nanomedicines for their potential clinical translations.

A thermosensitive, reactive oxygen species-responsive, MR409-encapsulated hydrogel ameliorates disc degeneration in rats by inhibiting the secretory autophagy pathway.

Lumbar disc degeneration is a common cause of chronic low back pain and an important contributor to various degenerative lumbar spinal disorders. However, currently there is currently no effective therapeutic strategy for treating disc degeneration. The pro-inflammatory cytokine interleukin-1ß (IL-1ß) mediates disc degeneration by inducing apoptotic death of nucleus pulposus (NP) cells and degradation of the NP extracellular matrix. Here, we confirmed that extracellular secretion of IL-1ß via secretory autophagy contributes to disc degeneration, and demonstrate that a thermosensitive reactive oxygen species (ROS)-responsive hydrogel loaded with a synthetic growth hormone-releasing hormone analog (MR409) can protect against needle puncture-induced disc degeneration in rats. Methods: The expression levels of proteins related to secretory autophagy such as tripartite motif-containing 16 (TRIM16) and microtubule-associated protein light chain 3B (LC3B) were examined in human and rat disc tissues by histology and immunofluorescence. The effects of TRIM16 expression level on IL-1ß secretion were examined in THP-1 cells transfected with TRIM16 plasmid or siRNA using ELISA, immunofluorescence, and immunoblotting. The in vitro effects of MR409 on IL-1ß were examined in THP-1 cells and primary rat NP cells using ELISA, immunofluorescence, immunoblotting, and qRT-PCR. Further, MR409 was subcutaneously administered to aged mice to test its efficacy against disc degeneration using immunofluorescence, X-ray, micro-CT, and histology. To achieve controllable MR409 release for intradiscal use, MR409 was encapsulated in an injectable ROS-responsive thermosensitive hydrogel. Viscosity, rheological properties, release profile, and biocompatibility were evaluated. Thereafter, therapeutic efficacy was assessed in a needle puncture-induced rat model of disc degeneration at 8 and 12 weeks post-operation using X-ray, magnetic resonance (MR) imaging, histological analysis, and immunofluorescence. Results: Secretory autophagy-related proteins TRIM16 and LC3B were robustly upregulated in degenerated discs of both human and rat. Moreover, while upregulation of TRIM16 facilitated, and knockdown of TRIM16 suppressed, secretory autophagy-mediated IL-1ß secretion from THP-1 cells under oxidative stress, MR409 inhibited ROS-induced secretory autophagy and IL-1ß secretion by THP-1 cells as well as IL-1ß-induced pro-inflammatory and pro-catabolic effects in rat NP cells. Daily subcutaneous injection of MR409 inhibited secretory autophagy and ameliorated age-related disc degeneration in mice. The newly developed ROS-responsive MR409-encapsulated hydrogel provided a reliable delivery system for controlled MR409 release, and intradiscal application effectively suppressed secretory autophagy and needle puncture-induced disc degeneration in rats. Conclusion: Secretory autophagy and associated IL-1ß secretion contribute to the pathogenesis of disc degeneration, and MR409 can effectively inhibit this pathway. The ROS-responsive thermosensitive hydrogel encapsulated with MR409 is a potentially efficacious treatment for disc degeneration.

Adaptable hydrogel with reversible linkages for regenerative medicine: Dynamic mechanical microenvironment for cells.

Hydrogels are three-dimensional platforms that serve as substitutes for native extracellular matrix. These materials are starting to play important roles in regenerative medicine because of their similarities to native matrix in water content and flexibility. It would be very advantagoues for researchers to be able to regulate cell behavior and fate with specific hydrogels that have tunable mechanical properties as biophysical cues. Recent developments in dynamic chemistry have yielded designs of adaptable hydrogels that mimic dynamic nature of extracellular matrix. The current review provides a comprehensive overview for adaptable hydrogel in regenerative medicine as follows. First, we outline strategies to design adaptable hydrogel network with reversible linkages according to previous findings in supramolecular chemistry and dynamic covalent chemistry. Next, we describe the mechanism of dynamic mechanical microenvironment influence cell behaviors and fate, including how stress relaxation influences on cell behavior and how mechanosignals regulate matrix remodeling. Finally, we highlight techniques such as bioprinting which utilize adaptable hydrogel in regenerative medicine. We conclude by discussing the limitations and challenges for adaptable hydrogel, and we present perspectives for future studies.

A Nanomedicine Fabricated from Gold Nanoparticles-Decorated Metal-Organic Framework for Cascade Chemo/Chemodynamic Cancer Therapy.

The incorporation of new modalities into chemotherapy greatly enhances the anticancer efficacy combining the merits of each treatment, showing promising potentials in clinical translations. Herein, a hybrid nanomedicine (Au/FeMOF@CPT NPs) is fabricated using metal-organic framework (MOF) nanoparticles and gold nanoparticles (Au NPs) as building blocks for cancer chemo/chemodynamic therapy. MOF NPs are used as vehicles to encapsulate camptothecin (CPT), and the hybridization by Au NPs greatly improves the stability of the nanomedicine in a physiological environment. Triggered by the high concentration of phosphate inside the cancer cells, Au/FeMOF@CPT NPs effectively collapse after internalization, resulting in the complete drug release and activation of the cascade catalytic reactions. The intracellular glucose can be oxidized by Au NPs to produce hydrogen dioxide, which is further utilized as chemical fuel for the Fenton reaction, thus realizing the synergistic anticancer efficacy. Benefitting from the enhanced permeability and retention effect and sophisticated fabrications, the blood circulation time and tumor accumulation of Au/FeMOF@CPT NPs are significantly increased. In vivo results demonstrate that the combination of chemotherapy and chemodynamic therapy effectively suppresses the tumor growth, meantime the systemic toxicity of this nanomedicine is greatly avoided.

Enhancement of tumour penetration by nanomedicines through strategies based on transport processes and barriers.

Nanomedicines for antitumour therapy have been widely studied in recent decades, but only a few have been used in clinical applications. One of the most important reasons is the poor tumour permeability of the nanomedicines. In this three-part review, intravascular, transvascular and extravascular transport were introduced one by one according to their roles in the overall process of nanomedicine transport into tumours. Transportation obstacles, such as elevated interstitial fluid pressure (IFP), abnormal blood vessels, dense tumour extracellular matrix (ECM) and binding site barriers (BSB), were each discussed in the context of the respective transport processes. Furthermore, homologous resolution strategies were summarized on the basis of each transportation obstacle, such as the normalization of blood vessels, regulation of the tumour microenvironment (TME) and application of transformable nanoparticles. At the end of this review, we propose holistic, concrete, and innovative views for better tumour penetration of nanomedicines.

Tumor microenvironment-responsive multifunctional peptide coated ultrasmall gold nanoparticles and their application in cancer radiotherapy.

Two important features are required for promising radiosensitizers: one is selective tumor cell targeting to enhance the therapeutic outcome via lethal DNA damage and the other is rapid clearance to enable excellent biocompatibility for potential clinical application. Herein, ultrasmall gold nanoparticles (Au NPs) with diameter smaller than 5 nm were prepared and covered with a multifunctional peptide to endow them with selective tumor cell uptake capability. Combined with X-ray irradiation, the responsive Au NPs demonstrated superior radio-sensitizing toxicity and rapid renal clearance in vivo. Methods: A responsive peptide (Tat-R-EK) consists of three build blocks were used: a cell and even nuclear penetrating block derived from human immunodeficiency virus-1 transactivator of transcription protein (Tat), an cathepsin B cleavable linker, and a zwitterionic antifouling block. Ultrasmall Au NPs were prepared and then covered by the peptide via the Au-S bonds between gold and thiol groups from cysteine. The morphology, colloidal stability and the responsiveness of obtained Au@Tat-R-EK NPs were studied using transmittance electron microscopy and dynamic laser scattering. The selective cancer cell uptake and accumulation of Au@Tat-R-EK NPs in cancer tissue were studied via ICP-MS in vitro and in vivo, respectively. The cytotoxicity of Au@Tat-R-EK NPs on HepG2 cancer cells was evaluated in terms of cell viability, DNA damage, intracellular reactive oxygen species generation, and apoptosis analysis. Finally, the biocompatibility and tumor destruction ability against orthotopic LM3 liver cancers were verified in vivo. Results: Multifunctional peptide modified ultrasmall Au NPs were successfully prepared. The Au NPs exhibited enough colloidal stability and cathepsin B-responsive surface change, leading to selectively uptake by cancer cells in vitro and accumulation to tumor sites in vivo. Combined with X-ray irradiation, the responsive Au NPs demonstrated superior radio-sensitizing cytotoxicity in vitro and therapeutic outcome on mouse liver cancer in vivo. The ultrasmall size enables rapid clearance of the Au NPs, guarantees the biocompatibility in vivo for potential clinical applications. Conclusion: Some obstacles faced by the Au NPs-based radiotherapy, such as short circulation half-life, non-specific distribution, slow clearance and low radio-sensitizing effect, were effective solved through rational design of the smart nanomedicine. This work provides new insight in designing tumor microenvironment-responsive nanomedicine in cancer radiotherapy.

The impact of size and surface ligand of gold nanorods on liver cancer accumulation and photothermal therapy in the second near-infrared window.

Gold nanorods (GNRs) with longitudinal surface plasmon resonance (LSPR) peaks in second near-infrared (NIR-II) window have attracted a great amount of attention as photothermal transducer because of their inherently excellent photothermal transition efficiency, high biocompatibility and versatile surface functionalization. One key question for the application of these GNRs against tumors in vivo is which size/shape and surface ligand conjugation are promising for circulation and tumor targeting. In this study, we prepared a series of gold nanorods (GNRs) of similar aspect ratio and LSPR peaks, and thus similar photothermal transfer efficiency under irradiation of 980 nm laser, but with tunable size in width and length. The obtained GNRs were subjected to surface modification with PEG and tumor targeting ligand lactoferrin. With these tailor-designed GNRs in hand, we have the chance to study the impact of dimension and surface property of the GNRs on their internalization via tumor cells, photothermal cytotoxicity in vitro, blood circulation and tissue distribution pattern in vivo. As a result, the GNRs with medium size (70 nm in length and 11.5 nm in width) and surface PEG/LF modification (GNR70@PEG-LF) exhibit the fastest cell internalization via HepG2 cells and best photothermal outcome in vitro. The GNR70@PEG-LF also display long circulation time and the highest tumor accumulation in vivo, due to the synergetic effect of surface coating and dimension. Finally, tumor ablation ability of the GNRs under irradiation of 980 nm light were validated on mice xenograft model, suggesting their potential photothermal therapy against cancer in NIR-II window.

In situ synthesis of poly (γ- glutamic acid)/alginate/AgNP composite microspheres with antibacterial and hemostatic properties.

In the present work, a poly(γ-glutamic acid)/alginate/silver nanoparticle (PGA/Alg/AgNP) composite microsphere with excellent antibacterial and hemostatic properties was prepared by the in situ UV reduction and emulsion internal gelation method, and its potential application for antibacterial hemostatic dressing was explored. Well dispersed AgNPs were in situ synthesized by a UV reduction method with alginate as stabilizer and reductant. The AgNPs showed excellent antibacterial activities against both gram-negative and gram-positive bacteria. Additionally, the AgNPs prepared by the in-situ UV reduction exhibited better biocompatibility and antibacterial effects than those prepared by the conventional chemical reduction method. PGA/Alg/AgNP composite microspheres were then prepared with the AgNPs by an emulsion internal gelation method. Such microspheres were found to be a porous and hollow network with pH-sensitive swelling properties and excellent hemostatic performance, indicating its application potentials as an advanced antibacterial hemostatic material.

Preparation of hydroxylated lecithin complexed iodine/carboxymethyl chitosan/sodium alginate composite membrane by microwave drying and its applications in infected burn wound treatment.

Improving the antibacterial properties of membrane wound dressings of natural polymers is crucial. Iodine is an important safe inorganic antibacterial agent, but was confined in the composition with polymer membranes due to the challenges of homogeneity and stability during drying. In the present work, iodine was complexed with hydroxylated lecithin (HL) to improve its stability and complexing efficiency for the composition with carboxymethly chitosan/sodium alginate. With the aid of microwave drying, hydroxylated lecithin complexed iodine/carboxymethly chitosan/sodium alginate (HLI/CMCS/SA) composite membranes with homogeneously distributions of HLI, high contents of activated iodine, good mechanical and swelling properties, proper water vapor permeability, pH controllable iodine release and excellent antibacterial properties were prepared. The composite membranes exhibited high repairing efficiencies for the infection of a rat model of the seawater immersed wound infection of deep partial-thickness burns. This novel antibacterial composite membrane can be potentially used as a high performance wound dressing for treating and repairing open trauma infections.

Preparation of the chitosan/poly(glutamic acid)/alginate polyelectrolyte complexing hydrogel and study on its drug releasing property.

In the current study, a novel semi-dissolution/acidification/sol-gel transition (SD-A-SGT) method was explored for the preparation of polyelectrolyte complexing (PEC) composite hydrogels with natural polymers only. A chitosan (CS) powder was uniformly dispersed in a solution of poly(glutamic acid) (PGA) and alginate (SA) to form a semi-dissolved slurry mixture that was then exposed to an gaseous acidic atmosphere. CS was gradually dissolved and interacted with PGA and SA to form a CS/PGA/SA PEC composite hydrogel with a homogeneous structure. The SD-A-SGT procedure was able to overcome the shortcomings of direct mixing method via the PEC interaction. The effects of the hydrogel composition on its structure and properties were investigated by FTIR, XRD, rheology study, XPS, SEM, and swelling kinetics. The drug delivery performance of the CS/PGA/SA hydrogel was explored using piroxicam (PXC) as a model drug. PXC was in situ embedded in the hydrogel by the SD-A-SGT method. The hydrogel exhibited pH responsive drug release behaviors that were affected by the hydrogel composition. In all, the SD-A-SGT method for preparing PEC composite hydrogels has a great application potential in constructing the CS based hydrogels as medical materials.

Bioresponsive Materials for Drug Delivery Based on Carboxymethyl Chitosan/Poly(γ-Glutamic Acid) Composite Microparticles.

Carboxymethyl chitosan (CMCS) microparticles are a potential candidate for hemostatic wound dressing. However, its low swelling property limits its hemostatic performance. Poly(γ-glutamic acid) (PGA) is a natural polymer with excellent hydrophilicity. In the current study, a novel CMCS/PGA composite microparticles with a dual-network structure was prepared by the emulsification/internal gelation method. The structure and thermal stability of the composite were determined by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). The effects of preparation conditions on the swelling behavior of the composite were investigated. The results indicate that the swelling property of CMCS/PGA composite microparticles is pH sensitive. Levofloxacin (LFX) was immobilized in the composite microparticles as a model drug to evaluate the drug delivery performance of the composite. The release kinetics of LFX from the composite microparticles with different structures was determined. The results suggest that the CMCS/PGA composite microparticles are an excellent candidate carrier for drug delivery.

Preparation, Characterization and Properties of Alginate/Poly(γ-glutamic acid) Composite Microparticles.

Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly(γ-glutamic acid) (PGA) is a natural polymer with high hydrophility. In the current study, novel Alg/PGA composite microparticles with double network structure were prepared by the emulsification/internal gelation method. It was found from the structure characterization that a double network structure was formed in the composite microparticles due to the ion chelation interaction between Ca2+ and the carboxylate groups of Alg and PGA and the electrostatic interaction between the secondary amine group of PGA and the carboxylate groups of Alg and PGA. The swelling behavior of the composite microparticles was significantly improved due to the high hydrophility of PGA. Influences of the preparing conditions on the swelling behavior of the composites were investigated. The porous microparticles could be formed while compositing of PGA. Thermal stability was studied by thermogravimetric analysis method. Moreover, in vitro cytocompatibility test of microparticles exhibited good biocompatibility with L929 cells. All results indicated that such Alg/PGA composite microparticles are a promising candidate in the field of wound dressing for hemostasis or rapid removal of exudates.

Preparation and characterization of chitosan physical hydrogels with enhanced mechanical and antibacterial properties.

The chitosan physical hydrogels formed under gaseous ammonia atmospheres usually have poor mechanical properties and low antibacterial activities, which limit its application as biomaterials. In the current study, CTS-Ag+/NH3 physical hydrogels with great comprehensive properties were prepared by the gelation of chitosan in the presence of AgNO3 under a gaseous ammonia atmosphere. Compared with the previously reported hydrogels made with chitosan and AgNO3, the CTS-Ag+/NH3 hydrogels were more homogeneous and transparent. In addition, the AgNO3 content in the hydrogels was decreased to 0.064-0.424wt.%. The formation mechanism and the influence of reaction conditions on the structures and properties of CTS-Ag+/NH3 physical hydrogels were characterized by FT-IR, SEM, XPS, XRD and rheological measurement. Tensile testing suggested that CTS-Ag+/NH3 physical hydrogels had a higher tensile strength than the CTS/NH3 hydrogel. Moreover, the CTS-Ag+/NH3 physical hydrogels showed excellent antibacterial activities against both gram positive and negative bacteria.