Calcium alginate/dextran methacrylate IPN beads as protecting carriers for protein delivery

In the present study, mechanical and protein delivery properties of a system based on the interpenetration of calcium-alginate (Ca-Alg) and dextran-methacrylate (Dex-MA) networks are shown. Interpenetrated hydrogels beads were prepared by means of the alginate chains crosslinking with calcium ions, followed by the exposure to UV light that allows the Dex-MA network formation. Optical microscope analysis showed an average diameter of the IPN beads (Ca-Alg/Dex-MA) of 2?mm. This dimension was smaller than that of Ca-Alg beads because of the Dex-MA presence. Moreover, the strength of the IPN beads, and of their corresponding hydrogels, was influenced by the Dex-MA concentration and the crosslinking time. Model proteins (BSA and HRP) were successfully entrapped into the beads and released at a controlled rate, modulated by changing the Dex-MA concentration. The enzymatic activity of HRP released from the beads was maintained. These novel IPN beads have great potential as protein delivery system.     

聚（AA-co-AM）／壳聚糖IPN超大孔水凝胶的制备及性能

以丙烯酸、丙烯酰胺为基体,壳聚糖为添加物,N,N’-亚甲基双丙烯酰胺、戊二醛为复合交联剂,利用水溶液聚合法和发泡技术制备了聚(丙烯酸-丙烯酰胺)/壳聚糖互穿网络超大孔水凝胶。采用差示扫描量热法(DSC)、红外光谱(FT-IR)和扫描电镜(SEM)等分析技术进行了表征,研究了水凝胶的溶胀行为和凝胶压缩强度。实验结果表明,该互穿网络超大孔水凝胶具有较快的溶胀速率和较好的凝胶强度。     

甲壳型液晶高分子PBPCS与IPN聚丙烯酸酯三元共混及阻尼性能研究

通过原位复合技术把甲壳型液晶高分子PBPCS分散到核-壳结构的聚丙烯酸酯中制备PBPCS与IPN聚丙烯酸酯三元共混阻尼材料。由IR光谱、TEM透射电镜初步认为PBPCS被包裹在IPN聚丙烯酸酯聚合物中,但PBPCS的加入会影响到核壳粒子结构的正常形态。通过DMA实验得到耗散因子曲线表明,加入PBPCS的三元共混物在高温区的最大耗散因子提高到0.9以上,表明甲壳型液晶高分子PBPCS在一定程度上增加IPN聚丙烯酸酯的阻尼能力,同时从体系中分子链相对运动对这一现象做出解释。     

Magnetic N-succinyl chitosan/alginate beads for carbamazepine delivery

Context: Epilepsy is a chronic condition characterized by recurrent unprovoked seizures. The most optimal use of drugs was limited due to their widespread systemic and central side effects. In contrast, focal drug delivery to epileptogenic focus based on superparamagnetic carrier is considered to be a promising and safe alternative. This delivery system could arrive exactly at the targeted tissue and deliver the loaded drug there with the help of an external magnetic field. Objective: A new magnetic delivery system was established to inhibit paradoxical discharge once the onset of seizures. Materials and methods: Carbamazepine was incorporated into N-succinyl chitosan (NSC)/alginate hydrogel beads by ionic interaction. The characteristics of the beads including morphology, release behavior, and magnetic property were also investigated. Results: Acceptable spherical morphology, excellent slow-release property, and superparamagnetic property of the NSC/alginate hydrogel beads were observed. Discussion and conclusion: The magnetic NSC/alginate beads may be acted as a sustained-release formulation. The drugs exhibit the potential magnetic property owing to Fe3O4 particles. It is promising that the released drugs are induced by the weak magnetic field of epileptogenic zone and have the potential of locating them so as to inhibit paradoxical discharge once the onset of seizures.     

Injectable thermogelling chitosan for the local delivery of bone morphogenetic protein

The aim of the present study was to evaluate the in vivo biocompatibility of injectable thermo gelling chitosan-ammonium hydrogen phosphate solution (chitosan-AHP) and its efficacy to deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) in a bioactive form. The thermogel showed a typical foreign body response upon subcutaneous implantation surrounded by a fibrous capsule. Even at 4 and 8?weeks post implantation, significant neutrophil infiltration was observed within the gel. Chitosan-AHP gel retained most of the loaded rhBMP-2 after a small initial release. The bioactivity of the released protein was demonstrated in vitro by the increase in alkaline phosphatase activity of mouse pre osteoblast cells (MC3T3-E1). Histological and micro-computed tomography (μCT) evaluation showed evidence of ectopic bone formation upon 4?μg/mL rhBMP-2 loaded chitosan-AHP injection. The study demonstrated a neutrophil mediated local tissue response to chitosan-AHP gel and its ability to encapsulate and maintain the bioactivity of rhBMP-2.     

Development of phosphorylated glucomannan-coated chitosan nanoparticles as nanocarriers for protein delivery

The aim of the present work was to develop a new nanoparticle carrier, adapted for the oral administration of proteins and their delivery to the immune system. Chitosan and phosphorylated glucomannan were chosen as major constituents of the nanoparticles. Chitosan nanoparticles were formed by ionic gelation and then coated with glucomannan. Two different protocols were adopted for the formation of the glucomannan coating: protocol I, in which chitosan nanoparticles were isolated before their coating; protocol II, in which chitosan nanoparticles were not isolated, but coated with glucomannan in the presence of free chitosan. The results showed that, under the selected formulation conditions, the sizes of the nanoparticles ranged between 170 and 300 nm and their zeta potential values were inverted from positive to negative by the glucomannan coating. The nanoparticles prepared by the two protocols could be freeze-dried, in the presence or absence of cryoprotective agents, preserving their original characteristics. The results of the stability study evidenced the positive role of the glucomannan coating in preventing the aggregation of the nanoparticles in buffered media. Finally, the association of the inmunomodulatory protein complex P1 to the chitosan-glucomannan nanoparticles was investigated. The results showed that the association was not dependent on the chitosan: sodium tripoliphosphate ratio, but it was significantly affected by the presence of sodium phosphate in the protein structure.     

Two-step synthesis of polyacrylamide/polyacrylate interpenetrating network hydrogels and its swelling/deswelling properties

A two-step polymerization technique is introduced to synthesize polyacrylamide/polyacrylate interpenetrating network (PAM/PAC IPN) hydrogels. The swelling ratio of the IPN hydrogel increases with the increase of the PAC content in PAM/PAC, and is smaller than the traditional PAM or PAC superabsorbents. A non-Fickian mechanism is observed in the swelling process, and the swelling changes from non-Fickian mechanism to Fickian mechanism with the increase of polyacrylate dosage in the hydrogel. The IPN hydrogel has typical pH-sensitivity and on–off effect. The deswelling properties and methyl orange dye removal are carried out based on the chelation of the carboxylic/carboxylate groups on the hydrogels with multivalent cations in solution. The hydrogel is expected to be used in the removal of heavy metal ions and dyes.     

Active nanodiamond hydrogels for chemotherapeutic delivery

Nanodiamond materials can serve as highly versatile platforms for the controlled functionalization and delivery of a wide spectrum of therapeutic elements. In this work, doxorubicin hydrochloride (DOX), an apoptosis-inducing drug widely used in chemotherapy, was successfully applied toward the functionalization of nanodiamond materials (NDs, 2-8 nm) and introduced toward murine macrophages as well as human colorectal carcinoma cells with preserved efficacy. The adsorption of DOX onto the NDs and its reversible release were achieved by regulating Cl- ion concentration, and the NDs were found to be able to efficiently ferry the drug inside living cells. Comprehensive bioassays were performed to assess and confirm the innate biocompatibility of the NDs, via real-time quantitative polymerase chain reaction (RT-PCR), and electrophoretic DNA fragmentation as well as MTT analysis confirmed the functional apoptosis-inducing mechanisms driven by the DOX-functionalized NDs. We extended the applicability of the DOX-ND composites toward a translational context, where MTT assays were performed on the HT-29 colon cancer cell line to assess DOX-ND induced cell death and ND-mediated chemotherapeutic sequestering for potential slow/sustained released capabilities. These and other medically relevant capabilities enabled by the NDs forge its strong potential as a therapeutically significant nanomaterial.     

Strong dual-crosslinked hydrogels for ultrasound-triggered drug delivery

Nano Research - Hydrogels that can respond to dynamic forces either from endogenous biological activities or from external mechanical stimuli show great promise as novel drug delivery systems...     

壳聚糖水凝胶的制备及性能研究

以壳聚糖为原料,用戊二醛作为交联剂,在醋酸溶液中合成壳聚糖水凝胶。用正交实验优化了制备壳聚糖水凝胶的工艺条件,实验结果表明:当壳聚糖浓度为3%、戊二醛浓度为3%、凝胶温度为55℃时制得的水凝胶硬度最大;当壳聚糖浓度为2%、戊二醛浓度为1%、凝胶温度为45℃时,制得的水凝胶溶胀度最大。壳聚糖水凝胶具有良好的生物相容性。     

空心羟基磷灰石亚微球/壳聚糖可注射水凝胶的制备及表征

采用W/O/W复乳法制备空心羟基磷灰石(HAP)亚微球,将空心HAP亚微球均匀分布在壳聚糖/甘油磷酸钠(CS/GP)体系中制备可注射HAP/CS水凝胶(gel 1),同时制备可注射CS水凝胶(gel 2).用X射线衍射仪、场发射透射电镜、红外光谱、扫描电镜对空心HAP亚微球和水凝胶进行了表征,并比较分析了两种溶胶的成胶...     

Quaternized chitosan/rectorite intercalative materials for a gene delivery system

Non-viral vectors have gained increasing attention in gene therapy because of their safety, but with the shortcoming of low transfection efficiency. We have developed a hybrid material as a novel non-viral vector, which combines the advantages of both biopolymer and clay in a gene delivery system. Quaternized chitosan was intercalated into the interlayers of rectorite to obtain a new polymer/layered silicate nanocomposite. In vitro and in vivo toxicity studies revealed that the nanocomposites were biocompatible and non-toxic. At the nanocomposite:pDNA mass ratio of 8:1, they achieved 100% pDNA adsorption capacity. In vitro cell transfection revealed a transfection efficiency of 32.1% at 96?h as shown by a flow-cytometric study, and the intensive green fluorescence protein (GFP) expression could last for up to 120?h. Furthermore, an in vivo transfection study showed that the most prominent GFP expression was observed in the gastric and duodenum mucosa, and good transfection efficiency was also obtained when injected into the muscle. All the results suggest that quaternized chitosan/rectorite nanocomposite is a novel and potential non-viral gene carrier.     

新型互穿网络超大孔水凝胶的制备、性能及表征

以丙烯酸、丙烯酰胺为基体，以乙烯基吡咯烷酮为预聚体，利用新型两步聚合法和发泡技术，制备了聚（丙烯酸．丙烯酰胺），聚乙烯基吡咯烷酮互穿网络超大孔水凝胶．采用差示扫描量热法（DSC）、红外光谱（FT-IR）和扫描电镜（SEM）等分析技术对所得水凝胶进行了表征，并研究了水凝胶的溶胀行为和凝胶强度．实验结果表明：该水凝胶具有相互连通的孔结构，溶胀行为在几分钟内即可完成；以新型两步法制备的互穿网络结构（IPN），大大提高了超大孔水凝胶的强度，新型两步法是制备IPN的有效方法之一．     

The preparation and characteristic of robust inorganic/organic IPN nanocomposite hydrogels with fast response rate

In order to prepare a robust thermosensitive hydrogels with ultrarapid response rate, the –Si–O– network was incorporated into the first clay cross-linked poly(N-isopropylacrylamide) network by the simultaneous hydrolytic polycondensation of tetramethoxysilane (TMOS); the two-step freezing polymerization technique was used in polymerization process for guaranteeing the very fast response rate of gels. The properties of resulting hydrogels (T-NC gels) including mechanical properties, hydrophily, swelling and response behavior show an obvious dependency on the content of added TMOS. With the increase of added TMOS, the more integrated and high-density –Si–O– network was formed in gels, which makes the gels become more robust with higher strength and modulus, while the swelling ratio and response rate decreases due to the lapped effect of increased network density and hydrophobicity. Interestingly, T-NC gels show better volume stability than that of NC gels in shrinking process.     

Cytocompatibility evaluation in cell-culture systems of chemically crosslinked chitosan/PVA hydrogels

In the present study we report the preparation, characterization and cytocompatibility of novel polymeric systems based on blends of chitosan and poly(vinyl alcohol) (PVA) and chemically crosslinked by glutaraldehyde for biomedical applications. The structure of the hydrogels was characterized through Fourier Transform Infrared spectroscopy (FTIR) and their swelling behavior was investigated as preliminary in vitro test. Bioactivity, cytotoxicity and cell viability were assessed via MTT assay with 2 cell cultures and cell spreading-adhesion analysis. Moreover, the cell viability and potential biocompatibility were assessed by the secretion of nitric oxide by activated macrophages with gamma interferon (IFN-γ) cytokine and lipopolysaccharide (LPS). It was found that by increasing the chitosan to PVA ratio the swelling behavior was significantly altered. In addition, all tested hydrogels have clearly presented adequate cell viability, non-toxicity and suitable properties which can be tailored for prospective use in tissue engineering.     

温敏性壳聚糖/甘油磷酸盐配合物凝胶的研究

采用壳聚糖与甘油磷酸盐分子组装的原理制备了具有温敏性的配合物凝胶体系,其在室温下呈液态,升温凝胶化.研究结果表明,α-甘油磷酸钠(α-GP)与β-甘油磷酸钠(β-GP)按一定比例混合与壳聚糖配合的体系,具有较宽的调节IGT的能力,可在更短的时间内凝胶,并且凝胶强度增大.当α-GP的混入比为30%w/w时,与未加入α-GP的体系相比,凝胶体系IGT可由37℃降低至29℃,并且体系在37℃下,可在200s内快速凝胶,强度可达到约0.51kPa.     

Mucoadhesive polymeric hydrogels for nasal delivery of acyclovir

The study evaluated different mucoadhesive polymeric hydrogels for nasal delivery of acyclovir. Gels containing poly-N-vinyl-2-pyrrolidone (PVP) were prepared with crosslinking achieved by irradiation with a radiation dose of 15 kGy being as efficient as 20 kGy. Gels containing chitosan and carbopol were also evaluated. The mucoadhesive properties of gels were measured by a modification of a classical tensile experiment, employing a tensile tester and using freshly excised sheep nasal mucosa. Considering the mucoadhesive force, chitosan gel and gel prepared with 3% PVP in presence of polyethylene glycol (PEG) 600 were the most efficient. The in vitro drug release depended on the gel composition. Higher release rates were obtained from PVP gels compared to chitosan or carbopol gels. The release rate of drug from PVP gels was increased further in presence of PEG or glycerol. Histopathological investigations proved that the PVP was a safe hydrogel to be used for mucosal delivery. The PEG in gel formulations caused less damages to the nasal mucosal compared to formulation containing glycerol.     

Biocompatibility and characteristics of chitosan/cellulose acetate microspheres for drug delivery

In this work, chitosan/cellulose acetate microspheres (CCAM) were prepared by the method of W/O/W emulsion with no toxic reagents. The microspheres were spherical, free flowing, and non-aggregated, which had a narrow size distribution. More than 90% of the microspheres had the diameter ranging from 200 to 280 μm. The hemolytic analysis indicated that CCAM was safe and had no hemolytic effect. The implanted CCAM did not produce any significant changes in the hematology of Sprague-Dawley (SD) rats, such as white blood cell, red blood cell, platelet, and the volume of hemoglobin. In addition, the levels of serum alanine aminotransferase, blood urea nitrogen, and creatinine had no obvious changes in SD rats implanted with CCAM, surger thread, or normal SD rats without any implantation. Thus, the CCAM had good blood compatibility and had no hepatotoxicity or renal toxicity to SD rats. Furthermore, CCAM with or without the model drug had good tissue compatibility with respect to the inflammatory reaction in SD rats and showed no significant difference from that of SD rats implanted with surgery thread. CCAM shows promise as a long-acting delivery system, which had good biocompatibility and biodegradability.     

Preparation and characterization of electrospun PCL/PLGA membranes and chitosan/gelatin hydrogels for skin bioengineering applications

In this study, two distinct systems of biomaterials were fabricated and their potential use as a bilayer scaffold (BS) for skin bioengineering applications was assessed. The initial biomaterial was a polycaprolactone/poly(lacto-co-glycolic acid) (PCL/PLGA) membrane fabricated using the electrospinning method. The PCL/PLGA membrane M-12 (12% PCL/10% PLGA, 80:20) displayed strong mechanical properties (stress/strain values of 3.01 ± 0.23 MPa/225.39 ± 7.63%) and good biocompatibility as demonstrated by adhesion of keratinocyte cells on the surface and ability to support cell proliferation. The second biomaterial was a hydrogel composed of 2% chitosan and 15% gelatin (50:50) crosslinked with 5% glutaraldehyde. The CG-3.5 hydrogel (with 3.5% glutaraldehyde (v/v)) displayed a high porosity, ≥97%, good compressive strength (2.23 ± 0.25 MPa), ability to swell more than 500% of its dry weight and was able to support fibroblast cell proliferation. A BS was fabricated by underlaying the membrane and hydrogel casting method to combine these two materials. The physical properties and biocompatibility were preliminarily investigated and the properties of the two biomaterials were shown to be complementary when combined. The upper layer membrane provided mechanical support in the scaffold and reduced the degradation rate of the hydrogel layer. Cell viability was similar to that in the hydrogel layer which suggests that addition of the membrane layer did not affect the biocompatibility.     

Preparation,fabrication and biocompatibility of novel injectable temperature-sensitive chitosan/glycerophosphate/collagen hydrogels

This paper introduces a novel type of injectable temperature-sensitive chitosan/glycerophosphate/collagen (C/GP/Co) hydrogel that possesses great biocompatibility for the culture of adipose tissue-derived stem cells. The C/GP/Co hydrogel is prepared by mixing 2.2% (v/v) chitosan with 50% (w/w) β-glycerophosphate at different proportions and afterwards adding 2 mg/ml of collagen. The gelation time of the prepared solution at 37°C was found to be of around 12 min. The inner structure of the hydrogel presented a porous spongy structure, as observed by scanning electron microscopy. Moreover, the osmolality of the medium in contact with the hydrogel was in the range of 310–330 mmol kg⁻¹. These analyses have shown that the C/GP/Co hydrogels are structurally feasible for cell culture, while their biocompatibility was further examined. Human adipose tissue-derived stem cells (ADSCs) were seeded into the developed C/GP and C/GP/Co hydrogels (The ratios of C/GP and C/GP/Co were 5:1 and 5:1:6, respectively), and the cellular growth was periodically observed under an inverted microscope. The proliferation of ADSCs was detected using cck-8 kits, while cell apoptosis was determined by a Live/Dead Viability/Cytotoxicity kit. After 7 days of culture, cells within the C/GP/Co hydrogels displayed a typical adherent cell morphology and good proliferation with very high cellular viability. It was thus demonstrated that the novel C/GP/Co hydrogel herein described possess excellent cellular compatibility, representing a new alternative as a scaffold for tissue engineering, with the added advantage of being a gel at the body’s temperature that turns liquid at room temperature.