Good Blood Compatibility Research Articles

Bio-responsive Bletilla striata polysaccharide-based micelles for enhancing intracellular docetaxel delivery

The aim of this study was to design a pH- and redox-dual responsive Bletilla striata polysaccharide (BSP)-based copolymer to enhance anti-tumor drugs release at tumor sites and improve the therapeutic effect. The copolymer was synthesized using stearic acid (SA) and cystamine via a disulfide linkage and characterized using 1H-Nuclear Magnetic Resonance spectroscopy and Fourier Transform Infrared spectroscopy. The BSP-ss-SA copolymer could self-assemble into micelle in an aqueous environment and could encapsulate docetaxel therein. Its inhibitory effects on HepG2 cells and 4 T1 cells were determined. Besides, the anti-cancer effects in vivo and histopathological study of 4 T1-bearing tumor mice were also evaluated. Docetaxel-loaded BSP-ss-SA micelles showed significant pH-sensitive release behavior, supplying a greater drug release percentage in pH 5.0 media compared to pH 7.4 media. BSP-ss-SA micelles exhibited a clear redox-responsive release property in pH 7.4 media whereas the similar cumulative release percentage of docetaxel from BSP-ss-SA micelles in pH 5.0 media in the presence and absence of DL-dithiothreitol. The Docetaxel-loaded BSP-ss-SA micelles clearly inhibited the proliferation of HepG2 and 4 T1 cells compared with docetaxel solution. The results of MTT and histopathological study indicated that BSP-ss-SA copolymer exhibited good blood compatibility. The BSP-ss-SA copolymer may be used as carriers to deliver anti-tumor drugs to special tumor tissues.

Effects of diameters and crystals of titanium dioxide nanotube arrays on blood compatibility and endothelial cell behaviors

Titanium dioxide nanotube arrays (TNTAs) have attracted extensive attention in the fields of biomaterials and biomedicine due to their unique tubular structure and good biocompatibility. In this paper, TNTAs with different nanotube diameters and lengths were in situ prepared on the titanium surface by the anodic oxidation, and their crystal structures were further changed by annealing treatment. The effects of TNTAs with different diameters and crystals on the blood compatibility and endothelial cell behaviors were investigated. The results showed that TNTAs with the diameter of 30∼90 nm can be obtained by controlling the anodization voltage, and annealing treatment did not obviously change the diameters and lengths of the nanotube arrays. However, annealing treatment can transform the amorphous TNTAs into the anatase structure. The diameter and crystal structure of the nanotube arrays played a key role in the surface wettability and protein adsorption. The nanotube array with larger diameter displayed better surface hydrophilicity as compared to the pristine titanium, and annealing treatment further enhanced the hydrophilicity. As compared to the pristine titanium, the nanotube array structure had the characteristic of selective protein adsorption, and the nanotube array can promote the bovine serum albumin (BSA) adsorption and prevent the fibrinogen (FIB) adsorption, however, the increase of nanotube diameter could reduce BSA adsorption and increase FIB adsorption. Besides, the nanotube array with anatase structure can promote BSA adsorption while reduce FIB adsorption. Therefore, the TNTAs with smaller diameter and anatase crystal had good blood compatibility and cell compatibility, they can not only reduce platelet adhesion and hemolysis rate but also increase endothelial cell adhesion and proliferation. In conclusion, the nanotube arrays of the present study can be used to improve the cell compatibility and blood compatibility of the titanium implants.

Fabrication of chitosan/graphene oxide composite aerogel microspheres with high bilirubin removal performance.

Functional chitosan/graphene oxide (CS/GO) composite aerogel microspheres were fabricated via CO2 supercritical drying, which displayed excellent performance for bilirubin removal. The morphology and chemical structure of CS/GO composite aerogel microspheres were characterized, which illustrated a nanoporous structure with a maximum specific surface area of 174.69 m2/g, and a special pore size distribution at 20-40 nm, also a good mechanical property. Importantly, the composite aerogel microspheres (10% GO) revealed a large adsorption capacity (178.25 mg/g) for bilirubin within 2 h. Dynamic adsorption experiment illustrated that the aerogel microspheres adsorbed much more bilirubin with a shorter equilibrium time of about 30 min. Besides, the adsorption mechanism of bilirubin by the CS/GO composite aerogel microspheres was investigated through the relevant model fitting, including adsorption kinetics and adsorption isotherm, which illustrated that the mechanism included both physical and chemical processes, but chemical adsorption was dominated. Adsorption isotherm indicated that bilirubin adsorption by the microspheres was fitted well with Freundlich isotherm, which ascribed to multilayer adsorption. After five adsorption-desorption cycles, the adsorption capacity still maintains large adsorption capacity. In addition, the hemolysis rate and coagulation time tests presented the good blood compatibility for the adsorbents. Therefore, the CS/GO composite aerogel microspheres with rapid, high adsorption capacity and good blood compatibility might be promising for hyperbilirubinemia treatment.

Biocompatibility and paclitaxel/cisplatin dual-loading of nanotubes prepared from poly(ethylene glycol)-polylactide-poly(ethylene glycol) triblock copolymers for combination cancer therapy

Nanotubes were prepared by self-assembly of the copolymer using co-solvent evaporation method. The biocompatibility of the nanotubes was assessed in comparison with spherical micelles and filomicelles prepared from poly(ethylene glycol)-poly(L-lactide-co-glycolide) (PEG-PLGA) and poly(ethylene glycol)-poly(L-lactide) (PEG-PLA), respectively. Several aspects of biocompatibility of the aggregates were considered, including agar diffusion and MTT assay, release of cytokines, hemolysis, protein adsorption, dynamic clotting in vitro, and Zebrafish embryonic compatibility in vivo. The nanotubes present good cell compatibility and blood compatibility in vitro, and almost no toxicity towards Zebrafish embryos development in vivo. Furthermore, dual-loading of hydrophilic cisplatin and hydrophobic paclitaxel was achieved in the nanotubes with high loading content and loading efficiency. The release of both drugs was slower from dual-loaded nanotubes than from single-loaded ones, but the total amount of released drugs in higher for dual-loaded nanotubes than from single-loaded ones. Cellular uptake and inhibition tests showed that the nanotubes were successfully taken up by tumor cells and effectively inhibited cell growth. It is thus concluded that PEG-PLA-PEG nanotubes with outstanding biocompatibility could be promising for co-delivery of hydrophilic and hydrophobic agents in combination cancer therapy.

Codelivery of doxorubicin and camptothecin by dual-responsive unimolecular micelle-based β-cyclodextrin for enhanced chemotherapy

Tumor microenvironment (TME)-induced drug delivery technology is a promising strategy for improving low drug accumulation efficiency, short blood circulation and weak therapeutic effect. In this work, a dual-responsive (reduction- and pH-responsive) polyprodrug nanoreactor based on β-cyclodextrin (β-CD) was constructed for combinational chemotherapy. Specifically, the dual-responsive star polymeric prodrug was synthesized by atom transfer radical polymerization (ATRP) based on a starburst initiator of β-CD-Br. The obtained polyprodrug contained a hydrophilic chain of poly-(ethylene glycol) methyl ether methacrylate (POEGMA) and a hydrophobic part of camptothecin (CPT) prodrug and poly[2-(diisopropylamino)ethyl methacrylate] (PDPA), denoted as β-CD-PDPA-POEGMA-PCPT (CCDO for short). The obtained CCDO could form stable unimolecular micelles, which could be efficiently internalized by cancer cells. To enhance the curative effect, the anticancer agent doxorubicin (DOX) could be encapsulated into the hydrophobic cavity of the CCDO by hydrophobic-hydrophobic interaction. In vitro drug release studies showed that the obtained CCDO/DOX micelles controlled the release of active CPT and DOX occurring in a reductive environment and at low pH. In vitro cytotoxicity results suggested that the anticancer efficacy of dual-responsive CCDO/DOX micelles was superior to that of CCDO micelles. In addition, in vivo results verified good blood compatibility of the unimolecular micelles. This integrated dual-responsive drug delivery system may solve the low drug loading and poor controlled release problems found in traditional polymer-based drug carriers, providing an innovative and promising route for cancer therapy.

Heparin coating on 3D printed poly (l-lactic acid) biodegradable cardiovascular stent via mild surface modification approach for coronary artery implantation

In the last decade, stent implantation therapy has been widely performed in the clinic. Although the patient's cardiovascular state depends on their age, gender, and health condition, the development of customized individual stents has been limited. Thus, a patient-specific stent manufacturing system should be devised for more successful stent therapy. In this study, we prepared a 3D printed PLA biodegradable polymeric stent using polydopamine (PDA), polyethyleneimine (PEI) and heparin (Hep) chemistry to prevent restenosis and thrombosis with anticoagulation and good blood compatibility. Physico-chemical characterization indicated that pristine PLA substrates were well modified as the amine abundant surface allowed for coating of a large amount of Hep. From in vitro and ex vivo analysis, heparinized 3D PLA stents showed excellent thromboresistance and hemocompatibility functions as well as modulation of smooth muscle cell (SMC) and endothelial cell (EC) proliferation. In an in vivo study, the heparinized 3D PLA stent showed the widest lumen area with the least neointimal hyperplasia and without atherosclerosis or thrombosis. All of these assessments clearly confirmed that our innovative strategy may suggest a useful paradigm as a preparation method for a patient-customized fully biodegradable individual stent for successful implantation therapy. This would find wide utilization for cardiovascular clinical applications.

Biological properties of mesoporous silica-rapamycin-heparin drug eluting stent

Objective Fabricating mesoporous silica-rapamycin-heparin drug-eluting stent (MRHES), and then evaluating its biological properties via in vitro and in vivo experiments. Methods The blood compatibility of MRHES was detected by haemolysis test and platelet adhesion test. We implanted MRHES and bare metal stent (BMS) into one of the rabbit carotid arteries respectively. After operation, they were sacrificed to take out specimens. The specimens were divided into two sections: the first segment were hematoxylin-eosin staining after they were sected to observe the intimal hyperplasia, and the second segment were scanned by electron microscopy to observe the endothelialization. Results MRHES had good blood compatibility. After 30 days, the average thickness of the intima was: BMS: (0.14±0.01) mm, MRHES: (0.08±0.01) mm, P<0.01. After 90 days, the average thickness of the intima was: BMS: (0.38±0.04) mm, MRHES: (0.20±0.03) mm, P<0.01. After 30 days, BMS was nearly completely endothelialized, but not MRHES. After 90 days, both of them were completely endothelialized. Conclusion MRHES showed excellent blood compatibility. It inhibited intimal hyperplasia in the early stage, but had little effect on endothelialization lately. Key words: Rapamycin; Heparin; Mesoporous silica; Drug-eluting stent; Intimal hyperplasia

Functionalized Biomimetic Composite Nanfibrous Scaffolds with Antibacterial and Hemostatic Efficacy for Facilitating Wound Healing.

An ideal wound dressing should not only promote rapid hemostasis and wound healing but also have good biocompatibility, antimicrobial activities, and should mimic the skin's physiological function. In the present study, five O-quaternized chitosan (QAS-CS) materials with satisfactory antibacterial activity and no cytotoxicity were successfully synthesized. Furthermore, we reported the synthesis and characterization of the two novel composite nanofibrous scaffolds consisting of selfdeveloped collagen (COL), quaternary ammonium salt (QAS) or QAS-CS and polycaprolactone (PCL) or polyvinyl alcohol (PVA) with an electrospinning approach. The PCL/COL/QAS (PCQ3) and PVA/COL/QAS-CS (PCQC5) materials exhibited uniform, three-dimensional interconnected pore structure, high porosity, and large specific surface area, which can mimic the architecture and biological functions of the native extracellular matrix microenvironment and provide suitable conditions for cell adhesion, proliferation, and differentiation. The growth and proliferation of human immortalized epidermal (HaCaT) cells on PCQ3 and PCQC5 materials was good, and the result of blood compatibility and the skin irritant test indicated that the scaffolds had good blood compatibility and did not exhibit significant irritability. Importantly, PCQ3 and PCQC5 have notable effects on rapid hemostasis, antibacterial activity, and anti-inflammation, promote wound healing, and display other superior benefits in comparison to available products. Overall, PCQ3 and PCQC5 are proposed to be good candidates for skin tissue engineering applications and can be used on different types of wounds.

TLyp-1-conjugated GSH-sensitive biodegradable micelles mediate enhanced pUNO1-hTRAILa/curcumin co-delivery to gliomas

The successful treatment of gliomas relies on two important factors, namely therapeutic genes/drugs and efficient delivery vehicles to cross the blood-brain barrier. In this work, a new gene vector was constructed based on polycaprolactone (PCL), glutathione (reduced; GSH)-sensitive polyethylenimine (PEI-SS) and polyethylene glycol (PEG), and modified with a cell-penetrating peptide (tLyp-1); this yielded tLyp-1-conjugated GSH-sensitive biodegradable micelles (PPPt) that mediated enhanced tumour necrosis factor (TNF)-related apoptosis-inducing ligand (pUNO1-hTRAILa) and curcumin (CUR) co-delivery to gliomas. The sensitisation function of CUR was used to explore whether CUR and genes have a synergistic antitumour effect. The results showed that the drug loading efficiency of PPPt was about 8.6%. The PPPt possessed good cytocompatibility and blood compatibility when the concentration was less than 0.06 mg/mL. PPPt strongly condensed pUNO1-hTRAILa to form a nanocomplex and efficiently transfected C6 cells. The drug-release behaviour of PPPt/CUR/pUNO1-hTRAILa was reduction-sensitive and the cellular uptake results indicate that modification of tLyp-1 promoted the internalisation of micelles. The PPPt/CUR/pUNO1-hTRAILa complexes exhibited much better in vitro and in vivo antitumour effects than micelles loaded with CUR or pUNO1-hTRAILa alone. We also used magnetic resonance imaging for in vivo monitoring of the transcranial drug delivery and therapeutic effect of the tumour on rats bearing in situ glioma.

New membranes based on polyethersulfone – SlipSkin™ polymer blends with low fouling and high blood compatibility

Hemodialysis is an important therapy for treating patients with End Stage Renal Disease (ESRD). These patients visit the hospital 3 times a week and each time their blood is cleansed during 4-hour dialysis sessions using a hollow fiber membrane module; also called artificial kidney. This device mainly achieves removal of small water-soluble toxins and a limited number of middle molecules. To improve the clearance of toxins, especially middle molecules and protein bound toxins, longer treatment via nocturnal dialysis and/or the application of portable/wearable artificial kidney is required. Such therapies require application of membranes with very low fouling and very good blood compatibility. Current membranes often contain hydrophilic additives which could elute during sterilization processes and/or during long-term filtration. In this study, we propose a simple method for developing low fouling blood compatible membranes by blending of polyethersulfone (PES), a material already used for fabrication of dialysis membranes, with small amounts of SlipSkin™ (SS), a blood compatible random copolymer of hydrophilic N-vinylpyrrolidone (NVP) and hydrophobic N-butylmethacrylate (BMA). Our results show that membranes with 2 wt% of SS have high fouling resistance to proteins and middle-size molecules and very good blood compatibility, making these membranes promising for application in dialysis therapy.

Construction of controllable polyethylene glycol bioactive coating with hemocompatibility from the surface of modified glass substrate

A diblock copolymer, poly(ethylene glycol) methacrylate-block-glycidyl methacrylate (PEGMA-GMA), was prepared on glass substrate by surface-initiated atom transfer radical polymerization (SI-ATRP), and endothelial specific peptide Arg-Glu-Asp-Val (REDV) was immobilized at the end of the PEGMA-GMA polymer brush by ring opening reaction through the rich epoxy groups in the GMA. The structure and hydrophilicity of the polymer brushes were characterized by static water contact angle, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The results showed that the REDV modified copolymer brushes were successfully constructed on the glass substrates. The REDV peptide immobilized onto surface was quantitatively characterized by ultraviolet-visible spectroscopy (UV-VIS). The blood compatibility of the coating was characterized by recalcification time and platelet adhesion assay. The results showed that the polymer coating had good blood compatibility. The multifunctional active polymer coating with PEGMA and peptide produced an excellent prospect in surface construction with endothelial cells selectivity.

An Albumin Biopassive Polyallylamine Film with Improved Blood Compatibility for Metal Devices.

Nowadays, a variety of materials are employed to make numerous medical devices, including metals, polymers, ceramics, and others. Blood-contact devices are one of the major classes of these medical devices, and they have been widely applied in clinical settings. Blood-contact devices usually need to have good mechanical properties to maintain clinical performance. Metal materials are one desirable candidate to fabricate blood-contact devices due to their excellent mechanical properties and machinability, although the blood compatibility of existing blood-contact devices is better than other medical devices, such as artificial joints and artificial crystals. However, blood coagulation still occurs when these devices are used in clinical settings. Therefore, it is necessary to develop a new generation of blood-contact devices with fewer complications, and the key factor is to develop novel biomaterials with good blood compatibility. In this work, one albumin biopassive polyallylamine film was successfully established onto the 316L stainless steel (SS) surface. The polyallylamine film was prepared by plasma polymerization in the vacuum chamber, and then polyallylamine film was annealed at 150 °C for 1 h. The chemical compositions of the plasma polymerized polyallylamine film (PPAa) and the annealed polyallylamine film (HT-PPAa) were characterized by Fourier transform infrared spectrum (FTIR). Then, the wettability, surface topography, and thickness of the PPAa and HT-PPAa were also evaluated. HT-PPAa showed increased stability when compared with PPAa film. The major amino groups remained on the surface of HT-PPAa after annealing, indicating that this could be a good platform for numerous molecules’ immobilization. Subsequently, the bovine serum albumin (BSA) was immobilized onto the HT-PPAa surface. The successful introduction of the BSA was confirmed by the FTIR and XPS detections. The blood compatibility of these modified films was evaluated by platelets adhesion and activation assays. The number of the platelets that adhered on BSA-modified HT-PPAa film was significantly decreased, and the activation degree of the adhered platelets was also decreased. These data revealed that the blood compatibility of the polyallylamine film was improved after BSA immobilized. This work provides a facile and effective approach to develop novel surface treatment for new-generation blood-contact devices with improved hemocompatibility.

Hydrophobically modified poly(vinyl alcohol)s as antithrombogenic coating materials

Hydrophobically modified poly(vinyl alcohol)s (hm-PVAs) with various alkyl chain lengths (3–12) were synthesized and were coated on poly(propylene) (PP) films. The blood compatibilities of the hm-PVAs-coated films were evaluated. The C6-PVA-coated PP film showed suppressed platelet adhesion as compared to the other hm-PVA-coated PP films, especially the 15C6-PVA-coated PP film, in which 30 mol% of OH groups were substituted by C6 groups. The fibrinogen adsorption was also inhibited on this film. The hydration water structure of the films was analyzed using differential scanning calorimetry (DSC). 15C6-PVA showed the highest (4.8 wt%) intermediate water (IW), and hence exhibited good blood compatibility. The fibrinogen γ chain activity of the 15C6-PVA-coated PP film was 18% lower than that of the PP film, indicating that hm-PVAs can inhibit fibrinogen γ chain activation. These results showed that by simple hydrophobic modification, PVA could be used as a blood contacting material.

Structural control and characterization of hierarchically structured fibrous scaffolds

To prepare hierarchically structured fibrous scaffolds with different morphologies, and to explore the additional dimensionality for tuning the physicochemical properties of the scaffolds and the effect of their hemocompatibility and cytocompatibility. Electrospinning poly (e-caprolactone) (PCL)/polyvinylpyrrolidone (PVP) bicomponent fibers (PCL∶PVP mass ratios were 8∶2 and 5∶5 respectively), and the surface porous fibrous scaffolds were prepared by extracting PVP components. The scaffolds were labeled PCL-P8 and PCL-P5 respectively according to the mass ratio of polymer. In addition, shish-kebab (SK) structured scaffolds with different kebab sizes were created by solution incubation method, which use electrospun PCL fibers as shish while PCL chains in solution crystallizes on the fiber surface. The PCL fibrous scaffolds with smooth surface was established as control group. The hierarchically structured fibrous scaffolds were characterized by field emission scanning electron microspore, water contact angle tests, and differential scanning calorimeter (DSC) experiments. The venous blood of New Zealand white rabbits was taken and hemolysis and coagulation tests were used to characterize the blood compatibility of the scaffolds. The proliferation of the pig iliac artery endothelial cell (PIEC) on the scaffolds was detected by cell counting kit 8 (CCK-8) method, and the biocompatibility of the scaffolds was evaluated. Field emission scanning electron microscopy showed that porous morphology appeared on the surface of PCL/PVP bicomponent fibers after extracting PVP. In addition, SK structure with periodic arrangement was successfully prepared by solution induction, and the longer the crystallization time, the larger the lamellar size and periodic distance. The contact angle and DSC measurements showed that when compared with smooth PCL fiber scaffolds, the crystallinity of PCL surface porous fibrous scaffolds and PCL-SK fibrous scaffolds increased, while the hydrophobicity of PCL-SK fibrous scaffolds increased, but the hydrophobicity of PCL porous scaffolds did not change significantly. The hemolysis test showed that the hemolysis rate of PCL surface porous fibrous scaffolds and PCL-SK fibrous scaffolds was higher than that of PCL fibrous scaffolds. According to American Society of Materials and Tests (ASTM) F756-08 standard, all scaffolds were non-hemolytic materials and were suitable for blood contact materials. Coagulation test showed that the coagulation index of PCL surface porous fibrous scaffolds and PCL-SK fibrous scaffolds was higher than that of PCL fibrous scaffolds at 5 and 10 minutes of culture. CCK-8 assay showed that both hierarchically structured fibrous scaffolds were more conducive to PIEC proliferation than PCL fibrous scaffold. Based on electrospinning technology, solution-induced and blend phase separation methods can be used to construct multi-scale fiber scaffolds with different morphologies, which can not only regulate the surface physicochemical properties of the scaffolds, but also have good blood compatibility and biocompatibility. The hierarchically structured fibrous scaffolds have high application potential in the field of tissue engineering.

Chitosan-Chondroitin sulfate based polyelectrolyte complex for effective management of chronic wounds.

Acute and chronic wound remain an unresolved clinical problem among various demographic groups. Traditional marketed products focus mainly on inhibition of bacterial growth at the wound site neglecting the tissue repair, which significantly affect the healing rate. It would be highly beneficial if a wound healing material can be developed which has both antibacterial as well as tissue regenerating potential. We have prepared a polyelectrolyte complex (PEC) using chitosan (CH) and chondroitin sulfate (CS) which can form an in-situ scaffold by spontaneous mixing. The fabrication of CH-CS PEC was optimized using Quality-By-Design (QbD) approach. The prepared PEC showed very high swelling and porosity property. It was found to be non-hemolytic with good blood compatibility and low blood clotting index. It also exhibited good antibacterial activity against both gram-positive and gram-negative bacteria. The cell proliferation study exhibited good cytocompatibility and almost four-fold increase in cell density when treated with CH-CS PEC compared to control. In summary, we demonstrated that the prepared CH-CS PEC showed good blood compatibility, high antibacterial effect, and promoted wound healing potentially by stimulating fibroblast growth, making it an ideal wound dressing material.

Multifunctional Nanosystem Based on Graphene Oxide for Synergistic Multistage Tumor-Targeting and Combined Chemo-Photothermal Therapy.

Locating nanomedicines at the active sites plays a pivotal role in the nanoparticle-based cancer therapy field. Herein, a multifunctional nanotherapeutic is designed by using graphene oxide (GO) nanosheets with rich carboxyl groups as the supporter for hyaluronic acid (HA)-methotrexate (MTX) prodrug modification via an adipicdihydrazide cross-linker, achieving synergistic multistage tumor-targeting and combined chemo-photothermal therapy. As a tumor-targeting biomaterial, HA can increase affinity of the nanocarrier toward CD44 receptor for enhanced cellular uptake. MTX, a chemotherapeutic agent, can also serve as a tumor-targeting enhancer toward folate receptor based on its similar structure with folic acid. The prepared nanosystems possess a sheet shape with a dynamic size of approximately 200 nm and pH-responsive drug release. Unexpectedly, the physiological stability of HA-MTX prodrug-decorated GO nanosystems in PBS, serum, and even plasma is more excellent than that of HA-decorated GO nanosystems, while both of them exhibit an enhanced photothermal effect than GO nanosheets. More importantly, because of good blood compatibility as well as reduced undesired interactions with blood components, HA-MTX prodrug-decorated GO nanosystems exhibited remarkably superior accumulation at the tumor sites by passive and active targeting mechanisms, achieving highly effective synergistic chemo-photothermal therapeutic effect upon near-infrared laser irradiation, efficient ablation of tumors, and negligible systemic toxicity. Hence, the HA-MTX prodrug-decorated hybrid nanosystems have a promising potential for synergistic multistage tumor-targeting therapy.

Chemical and biological behaviours of hydrogels based on oxidized carboxymethylcellulose coupled to chitosan

Carboxymethylcellulose (CMC) was subjected to partial oxidation reaction by 2,2,6,6-tetramethylpiperidine-1-oxyl in the presence of sodium hypochlorite (NaOCl) and sodium bromide (NaBr). Hydroxylamine and acid–base assay methods were used to quantify the aldehyde and carboxyl groups, respectively. Chitosan (CS) was then coupled to CMC or oxidized CMC (OCMC). The carboxyl groups carried by CMC and the free amines by CS were estimated by potentiometry and conductimetry. Characterization and identification of the obtained materials were made by Fourier transform infrared spectroscopy, Ultraviolet–visible spectroscopy and X-ray fluorescence. The blood compatibility test shows that the haemolysis percentages of films are less than 5%, which indicates their good blood compatibility and their non-haemotoxicity. The anti-inflammatory activity reveals that the materials possess an ability to inhibit the denaturation of proteins. The mucoadhesion tests exhibit a marked increase in adhesion times of CMC/CS and OCMC/CS hydrogels on the intestinal mucosa. Besides, swelling behaviour and biodegradability were established.

Fabrication and characterization of hydroxyapatite/sodium alginate/chitosan composite microspheres for drug delivery and bone tissue engineering

Hydroxyapatite/sodium alginate/chitosan (HA/SA/CS) composite microspheres, which possess good biocompatibility for specific biomedical application, were prepared using an emulsion crosslink technique; calcium ions were used as a cross-linking agent. The effect of the concentration of sodium alginate (SA), the volume ratio of water to oil, the content of hydroxyapatite (HA) nanoparticles, as well as rotation speed, on the morphology and dispersion of composite microspheres were investigated. Also investigated were the drug loading, release behaviors, in vitro hemolysis activity, cytotoxicity, cell adhesion and proliferation capacity of the materials. The results demonstrate that the HA/SA/CS composite microspheres were successfully prepared; their drug loading and encapsulation efficiency are much higher than that of HA nanoparticles. Dox-loaded HA/SA/CS composite microspheres show good pH-sensitive drug-release capability. The hemolysis and cytotoxicity tests suggest that the microspheres have good blood and cell compatibility. Furthermore, the prepared composite microspheres display better cell adhesion and proliferation capacity than HA nanoparticles and HA/SA composite microspheres. Therefore, the HA/SA/CS composite microspheres might have potential as drug carriers in a pH-responsive controlled-release drug delivery system and as candidates for application in bone tissue engineering.

Extraction, Partial Identification and Bioactivities of Total Flavonoids from Carex meyeriana Kunth

To date, knowledge associated with extraction, chemical constituents and bioactivities of Total Flavonoids from Carex meyeriana Kunth (TFCMK) that remains unclear. Therefore, this paper was designed to optimize the ethanol reflux extraction method by response surface methodology and determine the chemical constituents by Liquid Phase-Mass Spectrometry (HPLC-MS); additionally, the bioactivities including antioxidant, antibacterial and hemolysis test were also explored. The maximum TFCMK extraction yield of 6.248%±0.016% was obtained under the optimal conditions as follows: Ethanol concentration 50%, ratio of liquid-to-solid 31 mL/g, extraction time 91 min and extraction temperature 71°C. Meanwhile, 9 compounds of TFCMK were identified by using LP-MS for the first time. In addition, TFCMK showed higher antioxidant activity compared with vitamin C, as evidenced by the lower EC50 or IC50 of TFCMK (reducing power assay: 0.125±0.025 mg/mL, DPPH radicals: 0.28±0.031, ABTS+ radicals:0.012±0.005, hydroxyl radicals: 0.028±0.008 mg/mL; The EC50 or IC50 of VC 0.156±0.012, 0.059±0.019, 0.068±0.024 and 0.032±0.007 mg/mL, respectively.). Broth microdilution assays had demonstrated that the minimal inhibitory concentrations (MICs) of TFCMK on Bacillus pumilus, Bacillus subtilis and Escherichia coli were 0.625±0.0032, 1.250±0.0216 and 5.000±0.0205 mg/mL, respectively. Besides, the hemolysis rate (less than 5%) in vitro implied that TFCMK possessed a good blood compatibility. In summary, this paper provides evidences that TFCMK might be applied as an antioxidant and antibacterial agent in the pharmaceutical and chemical industries.

Engineering multifunctional bioactive citric acid-based nanovectors for intrinsical targeted tumor imaging and specific siRNA gene delivery in vitro/in vivo

Targeted tumor imaging and efficient specific gene delivery in vivo has been one of the main challenges in gene-based cancer diagnosis and therapy. Herein, we engineered a citric acid-based polymer with intrinsical photoluminescence and gene loading capacity to achieve targeted delivery of siRNA and tumor imaging in vitro and in vivo. The multifunctional platform was formed from the self-assembling of poly (citric acid)-polymine conjugated with folic acid and rhodamine B (PPFR). PPFR showed stable photoluminescent ability and could effectively bind and protect the siRNA against RNase degradation. PPFR also exhibited good blood compatibility and cell compatibility against C2C12, MCF-7 and A549. Compared with commercial transfection agent Lipofectamine™ 2000, PPFR had a high cellular uptake, equivalent transfection efficiency and effectively down-regulated intracellular p65 expression in A549 cancer cells. Importantly, PPFR could efficiently accumulate and label the tumor tissue through the fluorescent imaging, selectively deliver siRNA into tumor tissue in vivo based on the tumor-bearing nude mice model. This work may provide a facile strategy to synthesize multifunctional biocompatible biomaterials for targeted tumor imaging and gene therapy.