The composite of methoxy polyethylene glycol (mPEG) and poly(lactic-co-glycolic acid) (PLGA) thermosensitive hydrogel mixed with various portions of hydroxyapatite (HAP) or β-tricalcium phosphate (β-TCP) were used as bone graft substitutes. The physical properties of a series of composite gels, including the critical micelle concentration (CMC), particle sizes, zeta potential, rheological behavior, morphology of composite gels, and sol–gel transition, were characterized in vitro. These composite gels could form a gel at body temperature and could be controlled easily at room temperature, but showed only a small decline in pH, to between 6.33 and 6.66, whereas mPEG–PLGA gel without ceramic exhibited a more significant decrease in pH over a period of 5 days. The dissolution of ceramics results in an increase in the concentration of calcium and phosphate, which can buffer the degradation of mPEG–PLGA. Higher cell viability was observed in the composite gels with more bioceramics, as shown in the MTT assay and the live and dead stain. Mixing mPEG–PLGA with HAP or β-TCP may hold greater promise than mPEG–PLGA alone for repairing bone defects. 相似文献
A partially biodegradable and thermosensitive hybrid hydrogel network (DAN series) based on dextran-allylisocyanate (Dex-AI) and poly(N-isopropylacrylamide) (PNIPAAm) was synthesized via UV photocrosslinking. These hybrid hydrogels were characterized in terms of their chemical structure, thermal, mechanical, morphological and temperature-induced swelling properties. The effect of the composition ratio of Dex-AI to PNIPAAm on such properties were examined. The differential scanning calorimetry data show that this Dex-AI/PNIPAAm hybrid network has an increased lower critical solution temperature (LCST) and glass transition temperature (Tg) with an increase in the Dex-AI content. The interior morphology of these hybrid hydrogels revealed a decreased porous microstructure with an increase in the Dex-AI content in the hybrid network. Furthermore, if the Dex-AI composition became too high, a distinctive network structure with two different microporous structures appeared. The mechanical properties of these hybrid hydrogels also increased with an increase in the Dex-AI content. The temperature dependence of the swelling ratio, the deswelling kinetics as well as the reswelling kinetics was also characterized by gravimetric method. When comparing with a normal PNIPAAm hydrogel, these Dex-AI/PNIPAAm hybrid networks, due to the presence of Dex-AI moiety, also show improved temperature-induced intelligent properties, such as the faster and controllable response dynamics, which may find promising applications in a wide variety of fields, such as biomedical and bioengineering fields. 相似文献
Delivery of biomacromolecular drugs into the inner ear is challenging, mainly because of their inherent instability as well as physiological and anatomical barriers. Therefore, protein-friendly, hydrogel-based delivery systems following local administration are being developed for inner ear therapy. Herein, biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing interferon α-2?b (IFN α-2?b) were loaded in chitosan/glycerophosphate (CS/GP)-based thermosensitive hydrogel for IFN delivery by intratympanic injection. The injectable hydrogel possessed a physiological pH and formed semi-solid gel at 37?°C, with good swelling and deswelling properties. The CS/GP hydrogel could slowly degrade as visualized by scanning electron microscopy (SEM). The presence of NPs in CS/GP gel largely influenced in vitro drug release. In the guinea pig cochlea, a 1.5- to 3-fold increase in the drug exposure time of NPs-CS/GP was found than those of the solution, NPs and IFN-loaded hydrogel. Most importantly, a prolonged residence time was attained without obvious histological changes in the inner ear. This biodegradable, injectable, and thermosensitive NPs-CS/GP system may allow longer delivery of protein drugs to the inner ear, thus may be a potential novel vehicle for inner ear therapy. 相似文献
Present study aims at synthesizing a thermosensitive hydrogel for controlled release of insulin. According to a modified method, hydroxybutyl chitosan (HBC) hydrogel possessed thermal sensitivity is prepared which can form hydrogel at over 25℃. The HBC hydrogel is non-cytotoxic to mice fibroblasts cells (L929). Insulin is 100% entrapped in the hydrogel, 38% of which is released in vitro from the concentration of 5% hydrogel after 48 h, whereas by enzymolysis with lysozyme, 80% of the total insulin is released after 48h. This study suggests that HBC hydrogel could be utilized for controlled release of insulin in a non-invasive manner. 相似文献
The design and synthesis of porous phosphate-gelatine composite implant which mimicks the structure of natural bone and has drug delivery function is proposed. Gelatine reproducing the proteinaceous part of bone was cross-linked in order to modulate its solubility in the physiologic fluids. The kinetic of gelatine release from ceramic matrix was also evaluated as model of the release of any therapeutic compound which can be loaded into gelatine. 相似文献
Sustained release thermosensitive solution containing cytarabine-loaded liposome delivery system offers the possibility of reduced dosing frequency and sustained drug action. Biodegradable and biocompatible chitosan-beta-glycerophosphate (C-GP) thermosensitive solution having the property to gel at body temperature and to maintain its physical integrity for longer period of time was used. The C-GP solution containing cytarabine-loaded liposomes (CGPCLL) was studied, and the results showed that the cytarabine liposomes were capable of high encapsulation efficiency (85.2 +/- 2.58%) with the mean diameter of 220 +/- 6.9 nm of extruded cytarabine-loaded liposome. Furthermore, transmission electron microscopy showed spherical-shaped liposomes after extrusion with smooth surface. In vitro studies of CGPCLL in PBS buffer showed that this system can sustain release of encapsulated drug for more than 60 h compared with drug-loaded liposomal suspension (upto 48 h). Pharmacokinetic studies of CGPCLL resulted in higher t(1/2) (28.86 h) and AUC 2526.88 mug/mL h compared with cytarabine-loaded liposomal suspension (CLLS) and C-GP containing free cytarabine (CGPFC) in rats. CGPCLL was capable of sustaining the cytarabine release for more than 60 h in vivo compared with CLLS and CGPFC which showed maximum amount of drug release within 42 and 10 h, respectively. Thus, these results showed that the CGPCLL gels at body temperature and can sustain the delivery of cytarabine effectively. 相似文献
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. 相似文献
A carboxymethyl derivative of scleroglucan (Scl-CM) with a derivatization degree of 65 ± 5% was synthesized. The rheological
behaviour of this novel polymer was studied and compared with that of the starting polymer. We observed that the charged moieties
carried on the chains could prevent the triple helix formation of Scl. Scl-CM aqueous solutions behave like true polymer solutions
up to 1% w/v, whereas above this concentration a weak gel behaviour was observed. CaCl2 addition to aqueous Scl-CM solutions led to a physical gel formation; the hydrogel strength was related to polymer and CaCl2 concentrations. Temperature sweeps, registered at 1 Hz on hydrogels differing in CaCl2 concentration, evidenced a gel → sol transition in the range of 30–40°C, depending on the molar ratio between carboxylic
groups and Ca+2. In order to verify a possible use of these hydrogels as drug delivery systems, acyclovir was loaded into the network. Rheological
analysis evidenced that the loaded drug can affect the hydrogel elastic modulus. The release of acyclovir in phosphate buffer
was evaluated at different temperatures in order to assess the suitability of this novel drug delivery system in topical applications. 相似文献
A poly (N-isopropylacrylamide) (PNIPA) hydrogel was synthesized by free radical polymerization and reinforced with a polyurethane foam
to make a hydrogel composite. The temperature dependence of the elastic modulus of the PNIPA hydrogel and the composite due
to volume phase transition was found using a uniaxial compression test, and the swelling property was investigated using an
equilibrium swelling ratio experiment. The gel composite preserves the ability to undergo the volume phase transition and
its elastic modulus has strong temperature dependence. The temperature dependence of the elastic modulus and swelling ratio
of the gel composite were compared to the PNIPA hydrogel. Not surprisingly, the modulus and swelling ratio of the composite
were less dramatic than in the gel. 相似文献
The aim of this study was to present a non-trypsin 3D cell culture method with a reversible thermosensitive HBCS hydrogel. In this study, hydroxybutyl chitosan (HBCS) was synthesized by grafting hydroxybutyl groups on chitosan molecule chains. The prepared HBCS was water-soluble, and the reversible phase transformation temperature was 26 °C. Scanning electron microscope images illuminated the 3-D network of hydrogel formed irregular porous structure which ranged from 50–250 μm. Cell viability assay indicated that HBCS solution could promote the proliferation of human umbilical vein endothelial cells (HUVECs), and the boost of proliferation was enhanced with the increase of HBCS concentration. HBCS had no harm to the nitric oxide (NO) synthesis functionality of HUVECs. HUVECs could grow and reproduce inside the hydrogel, and showed good vitality after 14-days culture. Meanwhile, cells cultured inside the hydrogel could be passaged successively through the reversible phase transformation process of HBCS. The results revealed that HBCS have the potential to be used for 3-D cell culture without the use of trypsin. 相似文献
In this work, the LTCC composite ceramics containing ??-alumina and quartz based on the binary system BaO?CB2O3 were prepared by traditional solid-state preparation process at a sintering temperature of 900 °C. Sintering mechanism and physical properties of the LTCC composite ceramics are investigated and discussed in detail in terms of their mineral phase composition. The results indicate that, by the chemical combination of barium hydroxide octahydrate and an aqueous solution of boric acid, a barium borate phase can be formed form the binary system BaO?CB2O3 and consequently supply a liquid sintering aid for the fabrication of LTCC composite ceramics at a sintering temperature of 900 °C. The introduction of ??-alumina to the binary system BaO?CB2O3 can improve the sintering behavior whereas the presence of quartz in the composite ceramics is important to achieve low permittivity. By the combination of ??-alumina, quartz and BaO?CB2O3 composition, the dense LTCC composite ceramics, which is characterized by excellent dielectric properties (permittivity: 3.56; 4.83; dielectric loss: 3 × 10?4; 4 × 10?4), can be fabricated availably. 相似文献
Ferroelectric ceramic particles based on lead titanate zirconate (PZT) were dispersed in a polymer matrix based on castor oil. After the poling process, the pyroelectric activity of this composite was measured using a direct method in which a linear heating rate was applied to the pre-poled samples. The pyroelectric coefficient at 343 K is comparable with that of a PZT–poly(vinylidene fluoride) (PVDF) composite and significantly higher than that of PVDF. 相似文献
Bone graft materials are applied in patients to augment bone defects and enable the insertion of an implant in its ideal position. However, the currently available augmentation materials do not meet the requirements of being completely resorbed and replaced by new bone within 3 to 6 months. A novel electrospun cotton-wool like material (Bonewool®, Zurich Biomaterials LLC, Zurich, Switzerland) consisting of biodegradable poly(lactic-co-glycolic) acid (PLGA) fibers with incorporated amorphous ß-tricalcium phosphate (ß-TCP) nanoparticles has been compared to a frequently used bovine derived hydroxyapatite (Bio-Oss®, Geistlich Pharma, Wolhusen, Switzerland) in vitro. The material composition was determined and the degradation behavior (calcium release and pH in different solutions) as well as bioactivity has been measured. Degradation behavior of PLGA/ß-TCP was generally more progressive than for Bio-Oss®, indicating that this material is potentially completely resorbable.
Local drug delivery strategies based on nanoparticles, gels, polymeric films, rods and wafers are increasingly used in cancer chemotherapy in order to enhance therapeutic effect and reduce systemic toxicity. Herein, a biodegradable and biocompatible in situ thermosensitive hydrogel was designed and employed to deliver tumor necrosis factor-α (TNF-α) locally by intratumoral injection. The triblock copolymer was synthesized by ring-opening polymerization (ROP) of β-butyrolactone (β-BL) and lactide (LA) in bulk using polyethylene glycol (PEG) as an initiator and Sn(Oct)2 as the catalyst, the polymer was characterized by NMR, gel permeation chromatography and differential scanning calorimetry. Blood and tumor pharmacokinetics and in vivo antitumor activity of TNF-α after intratumoral administration in hydrogel or solution with the same dose were evaluated on S180 tumor-bearing mice. Compared with TNF-α solution, TNF-α hydrogel exhibited a longer T1/2 (4-fold) and higher AUCtumor (19-fold), but Cmax was lower (0.5-fold), which means that the hydrogel formulation improved the efficacy with a lower systhemic exposure than the solution formation. In addition, TNF-α hydrogel improved the antitumor activity and survival due to lower systemic exposure than the solution. These results demonstrate that the in situ thermosensitive hydrogel-based local delivery system by intratumoral injection is well suited for the administration of TNF-α. 相似文献
Articular cartilage has limited repair capability following traumatic injuries and current methods of treatment remain inefficient. Reconstructing cartilage provides a new way for cartilage repair and natural polymers are often used as scaffold because of their biocompatibility and biofunctionality. In this study, we added degummed chopped silk fibers and electrospun silk fibers to the thermosensitive chitosan/glycerophosphate hydrogels to reinforce two hydrogel constructs which were used as scaffold for hyaline cartilage regeneration. The gelation temperature and gelation time of hydrogel were analyzed by the rheometer and vial tilting method. Mechanical characterization was measured by uniaxial compression, indentation and dynamic mechanical analysis assay. Chondrocytes were then harvested from the knee joint of the New Zealand white rabbits and cultured in constructs. The cell proliferation, viability, production of glycosaminoglycans and collagen type II were assessed. The results showed that mechanical properties of the hydrogel were significantly enhanced when a hybrid with two layers of electrospun silk fibers was made. The results of GAG and collagen type II in cell-seeded scaffolds indicate support of the chondrogenic phenotype for chondrocytes with a significant increase in degummed silk fiber–hydrogel composite for GAG content and in two-layer electrospun fiber–hydrogel composite for Col II. It was concluded that these two modified scaffolds could be employed for cartilage tissue engineering. 相似文献