Formulation and rheological evaluation of ethosome-loaded carbopol hydrogel for transdermal application

Objective: To select a suitable ethosome-loaded Carbopol hydrogel formulation, specifically tailored for transdermal application that exhibits (i) plastic flow with yield stress of approximately 50–80?Pa at low polymer concentration, (ii) relatively frequency independent elastic (G′) and viscous (G″) properties and (iii) thermal stability.

Methods: Carbopol (C71, C934, C941, C971 or C974) hydrogels were prepared by dispersing Carbopol in distilled water followed neutralization by sodium hydroxide. The effects of Carbopol grade, Carbopol concentration, ethosome addition and temperature on flow (yield stress and viscosity) and viscoelastic (G′ and G″) properties of Carbopol hydrogel were evaluated. Based on the aforementioned rheological properties evaluated, suitable ethosome-loaded Carbopol hydrogel was selected. In-vitro permeation studies of diclofenac using rat skin were further conducted on ethosome-loaded Carbopol hydrogel along with diclofenac-loaded ethosomal formulation as control.

Results: Based on preliminary screening, C934, C971 and C974 grades were selected and further evaluated for flow and viscoelastic properties. It was observed that ethosome-loaded C974 hydrogel at concentration of 0.50 and 0.75% w/w, respectively, demonstrated acceptable plastic flow with distinct yield stress and a frequency independent G′ and G″. Furthermore, the flow and viscoelastic properties were maintained at the 4, 25 and 32?°C. The results from in vitro skin permeation studies indicate that ethosome-loaded C974 hydrogel at 0.5% w/w polymer concentration exhibited similar skin permeation as that of ethosomal formulation.

Conclusion: The results indicate that suitable rheological properties of C974 could facilitate in achieving desired skin permeation of diclofenac while acting as an efficient carrier system for ethosomal vesicles.     

Evaluation of cross-linked chitosan microparticles containing metronidazole for periodontitis treatment

The aims of this study were to find the optimal formulation for the preparation of metronidazole-loaded chitosan microparticles (MTZ-MPs) via an emulsion cross-linking process, and to compare the in vitro release of MTZ from hydrogels and films containing the drug in forms of MTZ-MPs and raw powders. The effects of emulsifier type and concentration, amount of cross-linking agent, cross-linking time, drug:chitosan ratio, form of drug adding and washing method on the properties of the MTZ-MPs were investigated. The results indicated that the optimal conditions for round and free-flowing MTZ-MPs with a high percentage of entrapped drug and preferable release profile were 1% of Span80 in soybean oil, 5% of glutaraldehyde based on chitosan solution, 30 min of cross-linking time, 1:1 drug:chitosan ratio, drug adding in form of ethanol solution and washing with hexane only. MTZ-MPs prepared from the optimal formulation were incorporated in mucoadhesive hydrogel and film. The release profiles of the drug from hydrogel and film containing MTZ-MPs were in prolong pattern compared with those containing drug powders. However, the hydrogels exhibited higher preferable pattern of release profile than the films. Therefore, the hydrogel containing MTZ-MPs was possible to be further clinically investigated for peridontitis treatment.     

Bioactive injectable triple acting thermosensitive hydrogel enriched with nano-hydroxyapatite for bone regeneration: in-vitro characterization,Saos-2 cell line cell viability and osteogenic markers evaluation

Hydrogels forming in-situ have gained great attention in the area of bone tissue engineering recently, they were also showed to be a good and less invasive alternative to surgically applied ones. The primal focus of this study was to prepare chitosan-glycerol phosphate thermosensitive hydrogel formed in-situ and loaded with risedronate (bone resorption inhibitor) in an easy way with no requirement of complicated processes or large number of equipment. Then we investigated its effectiveness for bone regeneration. In-situ forming hydrogels were prepared using chitosan cross-linked with glycerol phosphate and loaded with risedronate and nano-hydroxyapatite as bone cement. The prepared hydrogels were characterized by analyzing their gelation time at 37?°C, % porosity, swelling index, in-vitro degradation, rheological properties, and in-vitro drug release. Results showed that the in-situ hydrogels prepared using 2.5% (w/v) chitosan cross-linked with 50% (w/v) glycerol phosphate in the ratio (9:1, v/v) reinforced with 20?mg/mL and nano-hydroxyapatite possessed the most sustained drug release profile. This optimized formulation was further evaluated using DSC and FTIR studies, in addition to their morphological properties using scanning electron microscopy. The effect on Saos-2 cell line viability was evaluated also using MTT assay on the optimized hydrogel formulation in addition to their action on cell proliferation using fluorescence microscope. Moreover, calcium deposition on the hydrogel and alkaline phosphatase activity were evaluated. Risedronate-nano-hydroxyapatite loaded hydrogels significantly enhanced the Saos-2 cell proliferation in addition to enhanced alkaline phosphatase activity and calcium deposition. Such results suggest that risedronate-nano-hydroxyapatite loaded hydrogels present great biocompatibility for bone regeneration. Proliferation of cells, as well as deposition of mineral on the hydrogel, was an evidence of the biocompatible nature of the hydrogel. This hydrogel formed in-situ present a good less invasive alternative for bone tissue engineering.     

Thermo-responsive methylcellulose hydrogels as temporary substrate for cell sheet biofabrication

Methylcellulose (MC), a water-soluble polymer derived from cellulose, was investigated as a possible temporary substrate having thermo-responsive properties favorable for cell culturing. MC-based hydrogels were prepared by a dispersion technique, mixing MC powder (2, 4, 6, 8, 10, 12 % w/v) with selected salts (sodium sulphate, Na₂SO₄), sodium phosphate, calcium chloride, or phosphate buffered saline, to evaluate the influence of different compositions on the thermo-responsive behavior. The inversion test was used to determine the gelation temperatures of the different hydrogel compositions; thermo-mechanical properties and thermo-reversibility of the MC hydrogels were investigated by rheological analysis. Gelation temperatures and rheological behavior depended on the MC concentration and type and concentration of salt used in hydrogel preparation. In vitro cytotoxicity tests, performed using L929 mouse fibroblasts, showed no toxic release from all the tested hydrogels. Among the investigated compositions, the hydrogel composed of 8 % w/v MC with 0.05 M Na₂SO₄ had a thermo-reversibility temperature at 37 °C. For that reason, this formulation was thus considered to verify the possibility of inducing in vitro spontaneous detachment of cells previously seeded on the hydrogel surface. A continuous cell layer (cell sheet) was allowed to grow and then detached from the hydrogel surface without the use of enzymes, thanks to the thermo-responsive behavior of the MC hydrogel. Immunofluorescence observation confirmed that the detached cell sheet was composed of closely interacting cells.     

Design and optimization of thermosensitive nanoemulsion hydrogel for sustained-release of praziquantel

Objective: This work aimed to develop an alternative sustained-release thermosensitive praziquantel-loaded nanoemulsion (PZQ-NE) hydrogel for better schistosomiasis treatment.

Significance: PZQ-NE-dispersed chitosan/glycerol 2-phosphate disodium/HPMC (NE/CS/β-GP/HMPC) hydrogel was successfully prepared to improve bioavailability of PZQ.

Methods: Solubility tests and pseudo-ternary phase diagrams were applied to screen optimal oils, surfactants and co-surfactants of NE. The hydrogels were characterized for gelling time, surface exudates, rheological properties and in vitro drug release. Formulation optimization of NE/CS/β-GP/HMPC hydrogel was conducted by Box–Behnken experimental design combined with response surface methodology. In vitro cytotoxicity of hydrogel was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method. The sustained-release property of PZQ in NE and optimized hydrogel was evaluated by pharmacokinetic study in rabbits.

Results: The formulation of PZQ-NE consisted of mass ratio of 12.5% capryol 90 containing PZQ (160?mg/g), 40% cremophor RH 40/tween 20 and transcutol HP (S/CoS?=?2:1), 47.5% deionized water. PZQ releasing from NE/CS/β-GP/HMPC hydrogels was best fitted to Higuchi model and governed by diffusion. Rheological investigation evidenced the themosensitive gelation of different hydrogel systems and their gel-like character at 37?°C. The optimized hydrogel formulation consisted of HPMC solution (103.69?mg/g), 3.03% (w/v) chitosan and 14.1% (w/v) β-GP showed no cytotoxicity when the addition of NE was no more than 100?mg/g. Pharmacokinetic parameters indicated that NE/CS/β-GP/HMPC hydrogel can significantly slow down drug elimination, prolong mean residence time and improve bioavailability of PZQ.

Conclusions: NE/CS/β-GP/HMPC hydrogel possessed sustained-release property and could be an alternative antischistosomal drug delivery system with improved therapeutic effect.     

Assessment of reinforced poly(ethylene glycol) chitosan hydrogels as dressings in a mouse skin wound defect model

Wound dressings of chitosan are biocompatible, biodegradable, antibacterial and hemostatic biomaterials. However, applications for chitosan are limited due to its poor mechanical properties. Here, we conducted an in vivo mouse angiogenesis study on reinforced poly(ethylene glycol) (PEG)-chitosan (RPC) hydrogels. RPC hydrogels were formed by cross-linking chitosan with PEGs of different molecular weights at various PEG to chitosan ratios in our previous paper. These dressings can keep the wound moist, had good gas exchange capacity, and was capable of absorbing or removing the wound exudate. We examined the ability of these RPC hydrogels and neat chitosan to heal small cuts and full-thickness skin defects on the backs of male Balb/c mice. Histological examination revealed that chitosan suppressed the infiltration of inflammatory cells and accelerated fibroblast proliferation, while PEG enhanced epithelial migration. The RPC hydrogels promoted wound healing in the small cuts and full layer wounds. The optimal RPC hydrogel had a swelling ratio of 100% and a water vapor transmission rate (WVTR) of about 2000 g/m²/day. In addition, they possess good mechanical property and appropriate degradation rates. Thus, the optimal RPC hydrogel formulation functioned effectively as a wound dressing and promoted wound healing.     

Preparation and pharmaceutical/pharmacodynamic evaluation of topical brucine-loaded liposomal hydrogel

To reduce the toxicity and enhance the therapeutic efficacy of brucine, a traditional Chinese medicine for relieving arthritic and traumatic pain, in this study, a novel brucine-loaded liposomal hydrogel (BLH) formulation, suitable for topical application, was developed. Spherical liposomes composed of lecithin and cholesterol, with brucine, was prepared by a modified ethanol-dripping method. High percentage (over 80%) of encapsulated brucine in liposomes was obtained. Topical liposomal hydrogel formulations were prepared by further incorporation of the prepared liposomes into structured carbopol 940 hydrogels with the concentration of carbopol 1.0%, the ratio of glycerol to carbopol 8:1 and the brucine content 0.1%. The liposomal hydrogel formulations provided an obvious promotion for skin permeation of bruicne while for the free brucine in hydrogels (BH), there was no detectable drug permeation through the skin. The safety evaluation showed that the prepared BLH were no irritation to both the broken and integrity skin. Pharmacodynamic evaluation revealed that the BLH showed a better therapeutic efficacy than that of the BH. So, it can be concluded that the BLH developed here could represent a safe, effective and promising transdermal formulation for local treatment of analgesic and anti-inflammatory disease.     

Controlled release behaviors of chitosan/α, β- glycerophosphate thermo-sensitive hydrogels

Chitosan/α, β-glycerophosphate (CS/α, β-GP) thermo-sensitive hydrogels presented flowable solution state at low temperature and semisolid hydrogel when the ambient temperature increased. In this research, different concentrations of metronidazole encapsulated, CS and α, β-GP, as well as different acid solvents, were chosen to evaluate their influences on the drug release behaviors from CS/α, β-GP hydrogels. It was found that there was a sustaining release during the first 3 h followed by a plateau. SEM images showed that drugs were located both on the surface and in the interior of hydrogels. The optimal preparation conditions of this hydrogel for drug release were as follows: 1.8% (w/v) CS in HAc solvent, 5.6% (w/v) α, β-GP and 5 g/L metronidazole encapsulation. Cytotoxicity evaluation found no toxic effect. In order to control the release rate, 2.5 g/L chitosan microspheres with spherical shape and smooth surface were incorporated, and it was found that the initial release process was alleviated, while drug concentration had no obvious effect on the release rate. It could be concluded that the metronidzole release behaviors could be optimized according to practical applications.     

Fabrication of chitosan/poly(ε-caprolactone) composite hydrogels for tissue engineering applications

The aim of this study was to fabricate three-dimensional (3D) porous chitosan/poly(ε-caprolactone) (PCL) hydrogels with improved mechanical properties for tissue engineering applications. A modified emulsion lyophilisation technique was developed to produce 3D chitosan/PCL hydrogels. The addition of 25 and 50 wt% of PCL into chitosan substantially enhanced the compressive strength of composite hydrogel 160 and 290%, respectively, compared to pure chitosan hydrogel. The result of ATR–FTIR imaging corroborated that PCL and chitosan were well mixed and physically co-existed in the composite structures. The composite hydrogels were constructed of homogenous structure with average pore size of 59.7 ± 14 μm and finer pores with average size of 4.4 ± 2 μm on the wall of these larger pores. The SEM and confocal laser scanning microscopy images confirmed that fibroblast cells were attached and proliferated on the 3D structure of these composite hydrogels. The composite hydrogels acquired in this study possessed homogeneous porous structure with improved mechanical strength and integrity. They may have a high potential for the production of 3D hydrogels for tissue engineering applications.     

Evaluation of Oil/Water-Type Cyclosporine Gel Ointment with Commercially Available Oral Solution

Oil/water-type cyclosporine (CyA) hydrogel ointment was evaluated as a candidate for the percutaneous application of CyA. The physical properties and the permeation profiles of 2% w/w CyA gel ointment were compared with other CyA ointments. All ointments used in this study were prepared with commercially available CyA (Sandimmune) oral solution, unlike the ointment reported in the publication of by Mizoguchi et al. The gel ointment required a surfactant corresponding to 5-7% w/w to obtain fine uniform particles. Mean diameter of oily particles in the gel ointment was 8.75 μm. The permeation of CyA from the ointments was investigated by using the abdominal skin of hairless rats in vitro. The percutaneous permeation of CyA was observed to be influenced by a variety of ointment bases used and by the presence of a stratum corneum which plays a role as the main barrier. In intact skin, the extent of permeation from the gel ointment was almost equivalent to that from Mizoguchi's ointment, which used the raw CyA. No permeation was observed in ointment bases with either white petrolatum or hydrophilic petrolatum, indicating values under the limit of detection (78 ng/ml) of the high-performance liquid chromatographic method used in this study. On the other hand, in stripped skin, differences in flux value of each ointment were shown. Those values increased in the following order: Mizoguchi's ointment, white petrolatum, hydrogel, hydrophilic petrolatum. From these results, hydrogel ointment seemed to be applicable for various skin diseases which respond to CyA. Of the physical properties, spreadability and consistency showed that gel ointment was superior to Mizoguchi's ointment. In stability tests, the gel ointment was stable with regard to particle size and residual CyA for 4 weeks. These results suggested that the oil/water-type CyA hydrogel ointment prepared in a combination with hydrogel and commercially available oral solution was useful for practical hospital preparations, with good physical properties, permeability, and stability.     

Swelling and mechanical behaviors of carbon nanotube/poly(vinyl alcohol) hybrid hydrogels

In this paper, carbon nanotubes (CNTs) were added into poly(vinyl alcohol) (PVA) hydrogels to modify their mechanical properties. A series of CNT/PVA hybrid hydrogels were prepared by freezing/thawing method. The mechanical and swelling properties of all hybrid hydrogels are better than those of the original PVA hydrogel. Especially, for CNTP-0.5 specimen with 0.5% w/w CNTs, its tensile modulus, tensile strength and strain at break are increased by 78.2%, 94.3% and 12.7%, respectively. And its swelling behavior is different from that of the pure PVA hydrogel. Its final swelling ratios at room temperature and 310 K are increased by 35.7% and 44.9%, respectively.     

pH-sensitive hydrogels based on semi-interpenetrating network (semi-IPN) of chitosan and polyvinyl pyrrolidone for clarithromycin release

The aim of this study was to develop a pH-sensitive chitosan/polyvinyl pyrrolidone (PVP) based controlled drug release system for clarithromycin. The hydrogels were synthesized by cross-linking chitosan and PVP blend with glutaraldehyde to form a semi-interpenetrating polymer network (semi-IPN). These semi-IPNs were studied for their content uniformity, swelling index (SI), mucoadhesion, wettability, in vitro release and their release kinetics. The hydrogels showed more than 97% content of clarithromycin. These hydrogels showed high swelling and mucoadhesion under acidic conditions. The swelling may be due to the protonation of a primary amino group on chitosan. In acidic condition, chitosan would be ionized, and adhesion could have occurred between the positively charged chitosan and the negatively charged mucus. In the alkaline condition, less swelling and mucoadhesion was noticed. In vitro release study revealed that formulation containing chitosan (2% w/v) and PVP (4% w/v) in the ratio of 21:4 showed complete drug release after 12 h. Release profile showed that all the formulations followed non-Fickian diffusion mechanism. The cross-linking and compatibility of clarithromycin in the formulation was studied by Fourier transform infrared (FTIR) spectroscopic analysis, differential scanning calorimetry (DSC) and powder X-ray diffraction (p-XRD) study, which confirmed proper formation of semi-IPN and stability of clarithromycin in the formulations. The surface morphology of semi-IPN was studied before and after dissolution in simulated gastric fluid (SGF, pH 1.2) which revealed pores formation in membrane after dissolution. The results of study suggest that semi-IPNs of chitosan/PVP are potent candidates for delivery of clarithromycin in acidic environment.     

Novel chitosan hydrogel formed by ethylene glycol chitosan, 1,6-diisocyanatohexan and polyethylene glycol-400 for tissue engineering scaffold: in vitro and in vivo evaluation

Traditional chitosan hydrogels were prepared by chemical or physical crosslinker, and both of the two kinds of hydrogels have their merits and demerits. In this study, researchers attempted to prepare one kind of chitosan hydrogel by slightly crosslinker, which could combine the advantages of the two kinds of hydrogels. In this experiment, the crosslinker was formed by a reaction between the isocyanate group of 1,6-diisocyanatohexan and the hydroxyl group of polyethylene glycol-400 (PEG-400), then the crosslinker reacted with the amidine and the hydroxyl group of ethylene glycol chitosan to form the network structure. Physical properties of the hydrogel were tested by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and biodegradation. Biocompatibility was assessed by cell implantation in vitro and the scaffold was used as a cartilage tissue engineering scaffold to repair a defect in rabbit knee joints in vivo. FTIR results show the formation of a covalent bond during thickening of the ethylene glycol chitosan. SEM and degradation experiments showed that the ethylene glycol chitosan hydrogel is a 3-D, porous, and degradable scaffold. The hydrogel contained 2 % ethylene glycol chitosan and 10 μl crosslinker was selected for the biocompatibility experiment in vitro and in vivo. After chondrocytes were cultured in the ethylene glycol chitosan hydrogel scaffold for 1 week cells exhibited clustered growth and had generated extracellular matrix on the scaffold in vitro. The results in vivo showed that hydrogel-chondrocytes promoted the repair of defect in rabbits. Based on these results, it could be concluded that ethylene glycol chitosan hydrogel is a scaffold with excellent physicochemical properties and it is a promising tissue engineering scaffold.     

In-situ forming biodegradable glycol chitosan-based hydrogels: Synthesis,characterization, and chondrocyte culture

In-situ forming hydrogels from thiolated glycol chitosan (GCH-SH) and vinyl sulfone-modified PEG (PL-VS) were designed, prepared and successfully applied as biodegradable, non-toxic bio-scaffolds for chondrocyte culture. The hydrogels could be formed in situ under physiological conditions via Michael-type addition between the GCH-SH and PL-VS at a low polymer concentration of 1–3% (w/v). Gelation times varied from 0.75 to 50 min, depending on the polymer concentration and the arm number of PEG-VS. Moreover, a high arm number and a high polymer concentration may lead to efficient network formation of GCH-SH/PEG-VS hydrogels. These hydrogels were found biodegradable in the presence of lysozyme, a cationic protein in the body, for a long period of time. Rheological studies indicated that these hydrogels generally displayed highly elastic property and had higher mechanical strength than those from thiolated hyaluronic acid/PEG-VS reported previously. SEM observation revealed that these hydrogels possessed well-interconnected microporous morphology. Besides these, the chondrocytes could be incorporated and homogeneously distributed in the hydrogel based on GCH-SH and 4-arm PL-VS. Importantly, after cell culture of 14 days, the chondrocytes in the hydrogel remained viable, as determined by a live–dead assay, and the cells kept their round chondrocytic phenotype. These results suggest that Michael-type addition is an effective method in the preparation of in-situ forming, biodegradable GCH-based hydrogels serving as bio-scaffolds for chondrocyte culture.     

pH-sensitive hydrogels based on semi-interpenetrating network (semi-IPN) of chitosan and polyvinyl pyrrolidone for clarithromycin release

The aim of this study was to develop a pH-sensitive chitosan/polyvinyl pyrrolidone (PVP) based controlled drug release system for clarithromycin. The hydrogels were synthesized by cross-linking chitosan and PVP blend with glutaraldehyde to form a semi-interpenetrating polymer network (semi-IPN). These semi-IPNs were studied for their content uniformity, swelling index (SI), mucoadhesion, wettability, in vitro release and their release kinetics. The hydrogels showed more than 97% content of clarithromycin. These hydrogels showed high swelling and mucoadhesion under acidic conditions. The swelling may be due to the protonation of a primary amino group on chitosan. In acidic condition, chitosan would be ionized, and adhesion could have occurred between the positively charged chitosan and the negatively charged mucus. In the alkaline condition, less swelling and mucoadhesion was noticed. In vitro release study revealed that formulation containing chitosan (2% w/v) and PVP (4% w/v) in the ratio of 21:4 showed complete drug release after 12?h. Release profile showed that all the formulations followed non-Fickian diffusion mechanism. The cross-linking and compatibility of clarithromycin in the formulation was studied by Fourier transform infrared (FTIR) spectroscopic analysis, differential scanning calorimetry (DSC) and powder X-ray diffraction (p-XRD) study, which confirmed proper formation of semi-IPN and stability of clarithromycin in the formulations. The surface morphology of semi-IPN was studied before and after dissolution in simulated gastric fluid (SGF, pH 1.2) which revealed pores formation in membrane after dissolution. The results of study suggest that semi-IPNs of chitosan/PVP are potent candidates for delivery of clarithromycin in acidic environment.     

Delivery of cefotaxime to the brain via intranasal administration

The purpose of this study was to investigate the plausibility of delivery of cefotaxime to the brain via intranasal administration. In vitro permeation studies were carried out using Franz diffusion cells, and the effect of different concentrations of chitosan (0.1% w/v and 0.25% w/v) on drug permeation across the bovine olfactory mucosa was determined. Samples were collected from the receiver compartment at different time points and analyzed using HPLC. The amount of cefotaxime that permeated across the olfactory mucosa when 0.25% w/v of chitosan was used as a permeation enhancer was ~1.5- and ~2-fold higher at the end of the first hour and second hour, respectively, over control (29.56 ± 6.18 μg/cm(2)). There was no significant enhancement in drug permeation when 0.1% w/v chitosan was used as the permeation enhancer. Pharmacokinetic studies were carried out using Sprague-Dawley rats. Cefotaxime solution with 0.25% w/v chitosan (40 mg/kg) was administered intravenously (i.v.) to rats in groups 1 and 3 and intranasally to those in group 2 and 4. The time course of drug in the brain was investigated by performing microdialysis in rats of groups 1 and 2. Blood samples were withdrawn from rats in groups 3 and 4, and cefotaxime in plasma was analyzed using HPLC after extraction with a hydrochloric acid-chloroform:1-pentanol (3:1) and phosphate buffer solvent system. Pharmacokinetic parameters were calculated using the trapezoidal rule. The results imply that the drug levels attained in the brain following i.v. and intranasal administrations were comparable. These results suggest that intranasal administration of cefotaxime could be a potential method of delivering antibacterial agents because of it being noninvasive and patient compliant.     

阴离子型高吸水性树脂凝胶的响应性能

以CMCTS-g-PAA和CMCTS-g-(PAANa-co-PVP)两类羧甲基壳聚糖改性阴离子型高吸水性树脂凝胶为研究对象,对其所吸收液体性能变化的响应性进行了研究。研究发现,阴离子型高吸水性树脂随乙醇/水混合溶剂中乙醇体积分数(φ)的增大发生体积相转变;随树脂结构中链段极性的增大,凝胶相变点相应的(φ)值降低;并随所吸收液体中低极性乙醇含量的增大,-COO-之间的相互排斥作用减弱,树脂的吸水速率降低。当研究溶液离子强度对树脂溶胀性能的影响时发现,1/S值较大时,离子强度与Q5/3成正比;但离子浓度较大时,Q5/3与1/S的线性关系消失。此外所吸收溶液的pH值对树脂的吸收率也有很大的影响。     

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.     

基于点击化学的壳聚糖水凝胶的制备及性能

本研究首先在甲磺酸中用丙烯酰氯对壳聚糖(CS)进行接枝改性,通过一步法合成了水溶性丙烯酰基壳聚糖(CS-AC)。之后,在光引发剂I2959和紫外光(UV)照下,以二硫苏糖醇(DTT)为交联剂制备了基于巯基-烯点击化学的CS-AC/DTT快速交联水凝胶。红外光谱(FTIR)和核磁共振氢谱(¹H-NMR)结果定性和定量地证明了100%左右的双键接枝率。与CS-CC-CS自交联水凝胶40min以上的交联时间相比,CS-AC/DTT点击化学水凝胶最短能在10min之内就凝胶完全,此时双键/巯基投料比为1∶0.5。测试表明该水凝胶具有5-10KPa左右的强度以及高达1415%的溶胀率。此外,水凝胶对小鼠成纤维细胞(NIH-3T3)无明显毒性,在物理负载了莫匹罗星后对耐甲氧西林金葡萄球菌(MRSA)具有良好的抗菌性。     

Differential physical, rheological, and biological properties of rapid in situ gelable hydrogels composed of oxidized alginate and gelatin derived from marine or porcine sources

Marine derived gelatin is not known to associate with any communicable diseases to mammals and could be a reasonable substitute for gelatin derived from either bovine or porcine sources. The low melting point of marine gelatin (8°C) also offers greater formulation flexibility than mammalian derived gelatins. However, the sub-optimal physical properties of marine gelatin generally limit the interest to further develop it for biomedical applications. This study aimed at investigating the feasibility of using oxidized alginate (Oalg) as a high activity macromolecular crosslinker of marine gelatin to formulate in situ gelable hydrogels with the goal of enhancing the latter’s physical properties. The performance of Oalg/marine gelatin hydrogel was compared to Oalg/porcine gelatin hydrogel; in general, the physicomechanical properties of both hydrogels were comparable, with the hydrogels containing porcine gelatin exhibiting moderately higher mechanical strengths with shorter gelation times, smaller size pores, and higher swelling ratios. On the contrary, the biological performances of the two hydrogels were significantly difference. Cells cultured in the marine gelatin derived hydrogel grew significantly faster, with greater than 60% more cells by 7 days and they exhibited more spread-out conformations as compared those cultured in the porcine derived hydrogel. Production of ECM by cells cultured in the Oalg/marine gelatin hydrogel was up to 2.4 times greater than that of in the Oalg/porcine gelatin hydrogel. The biodegradation rate of the hydrogel formulated from marine gelatin was greater than its counterpart prepared from porcine gelatin. These differences have important implications in the biomedical applications of the two hydrogels. Huijuan Liao and Hanwei Zhang are the first authors.