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@#A thermosensitive hydrogel system consisting of PLGA-PEG-PLGA hydrogel and Pseudomonas aeruginosa DNA vaccine was constructed and the immune efficacy of the system was evaluated. The PLGA-PEG-PLGA thermosensitive hydrogel containing Pseudomonas aeruginosa DNA vaccine was prepared by a simple physical mixing method. The gelation temperature, cytotoxicity, and release curve in vitro were tested.The degradability of hydrogel in vivo was evaluated. The mice were divided into control group (PBS), hydrogel group (Hydrogel), in vivo-jetPEI/plasmid DNA group (in vivo-jetPEI/pDNA), and hydrogel + in vivo-jetPEI/plasmid group (Gel+in vivo-jetPEI/pDNA). Mice were immunized three times with a ten-day interval. Two weeks after the last immunization, the mice were sacrificed. The proliferation of splenic lymphocytes, serum specific IgG antibodies and IFN-γ in supernatant of splenic lymphocytes were detected. The gelation temperature of PLGA-PEG-PLGA hydrogel was (32 ± 0.5) ℃. There was no obvious toxicity to cells in vitro, and about 80% of plasmid DNA was released after 7 days in vitro. PLGA-PEG-PLGA hydrogel was biodegradable, and degraded almost completely after 15 days in vivo. The spleen lymphocytes proliferated; the levels of specific IgG antibodies and IFN-γ of in vivo-jetPEI/pDNA and Gel+in vivo-jetPEI/pDNA groups increased. The hydrogel could enhance the immune response induced by DNA vaccine.Results suggest that the thermosensitive hydrogel system consisting of PLGA-PEG-PLGA hydrogel and Pseudomonas aeruginosa DNA vaccine is a promising new strategy for the development of PA vaccine.
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Aim To observe the immune regulation and cartilage protection of dexamethasone-loaded thermosensitive hydrogel (DLTH) on rheumatoid arthritis (RA) rats via conceiving a newly injectable sustained DLTH with chitosan-glycerin-borax as carrier. Methods Thirty rats were randomly divided into three groups, namely control, model and DLTH group. RA model was established through immune induction in model and DLTH group. From the 12th day, rats of DLTH group were injected with 40 (jlL DLTH (1 mg · kg
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Objective To explore the antibacterial activity and cytocompatibility of chitosan-nano-silver complex thermosensitive hydrogel. Methods There were 4 groups: group A (containing 1 ×10-5 chitosan-nano-silver complex thermosensitive hydrogel), group B (containing 5 ×10-6 chitosan-nano-silver complex thermosensitive hydrogel) , group C ( containing 2 ×10-6 chitosan-nano-silver complex thermosensitive hydrogel) , group D ( chitosan thermosensitive hydrogel ) .The antibacterial activity of the samples against six kinds of gram-negative bacteria, one kind of gram-positive bacterium, three kinds of fungi were measured by bacteriostatic circle.The cytocompatibility of the extraction to NIH-3T3 cells was studied by SRB. Results The antibacterial activity enhanced with the increasing of nano silver concentration in chitosan-nano-silver complex thermosensitive hydrogel, whose antibacterial activity was better than chitosan thermosensitive hydrogel; its extraction has no cytotoxicity, thus showed good cytocompatibility. Conclusion The chitosan-nano-silver complex thermosensitive hydrogel is a potential novel wound dressing.
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Objective To explored the therapeutic benefit and safety of acute kidney injury ( AKI) mice induced by ischemia/reperfusion ( I/R ) treating by thermosensitive chitosan chloride ( CSCI ) hydrogel, an injectable scaffold for adipose-derived MSCs ( ADMSCs ) delivery.Methods After establishing the rat model of acute kidney injury, all rats were randomly divided into 4 groups: ADMSCs/PBS group, ADMSCs/CSCI group, PBS group and CSCI group.Live/Dead staining was used to evaluate the Cytocompatibility between CSCI hydrogel and ADMSCs, dihydroethidium ( DHE) staining was used to detect the number of ROS in vivo, and bioluminescence imaging ( BLI) was used to track the retention and survival of ( fluc-mrfp) labeled ADMSCs in the rat kidney, respectively.The biocompatibility and biodegradability of CSCI hydrogel in kidney tissue were detected by HE staining.The improvement of renal function was evaluated by detecting the level of serum creatinine and urea nitrogen.Results Live/Dead staining manifested an satisfactory Cytocompatibility between CSCI hydrogel and ADMSCs.CSCI hydrogel can improve the micro-environment of AKI kidney tissue by lowering the level of ROS.In PBS and CSCI groups, the positive rate of DHE staining was 68.8%±8.5% and 38.5%±5.8%( P <0.05 ) , respectively.These suggested that CSCI hydrogels could improve the retention and survival of grafted ADMSCs.In ADMSCs /CSCI hydrogel group, BLI fluorescent signal can be detected on the seventh day and was undetectable on the 21st day.ROI value of BLI signal changed from 38 ×105 p/(s? cm2? sr) on the first day to 8.5 ×105 p/(s? cm2? sr) on the 14th day.In ADMSCs /PBS group, BLI fluorescent signal only can be detected on the seventh day and was undetectable on the 14th day.ROI value of BLI signal changed from 17 ×105 p/( s?cm2? sr) on the first day to 3.3 ×105 p/( s? cm2? sr) on the 14th day.Results detected on the 3th and 28th day suggested that ADMSCs/CSCI hydrogel group , ADMSCs/PBS group and CSCI hydrogel group have a better self-repairing capability than the PBS injection group ( P<0.05 ) .In addition, compared with the ADMSCs /PBS group and CSCI hydrogel group, ADMSCs /CSCI hydrogel group got a lower tissue injury scores (P<0.05).At the 4th week, significant improvement of the renal function was observed in CSCI hydrogels with ADMSCs groups.Conclusions CSCI hydrogel is a very promising cell carrier for the treatment of AKI.
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Objective To prepare triamcinolone acetonide acetate(TAA)thermosensitive hydrogel for intra-articular injection,and to investigate its release in vitro. Methods TAA suspending thermosensitive hydrogel was prepared by using poly lactic-co-glycolic acid(PLGA)-polyethylene glycol(PEG)-PLGA as gel matrices,xanthan gum as suspending agent and NaCl as flocculant. It was evaluated preliminarily by determining its contents and its in vitro release. Results The best compositions for preparation of TAA suspending thermosensitive hydrogel were 25% PLGA-PEG-PLGA,0.05% xanthan gum, 0.9% NaCl and 4 mg·mL-1 TAA.The gelation temperature was 35.3 ℃ .The average recovery was(98.98±0.31)%. By the method of membraneless dissolution,the accumulative drug release was up to 83. 31% at 16 days. The drug release followed Ritger-Peppas methematical model. Conclusion The TAA thermosensitive hydrogel with obviously sustained release is expected to become a new drug delivery system for intra-articular injection.
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OBJECTIVE:To optimize the formulation of Methotrexate thermosensitive hydrogels,and to study the in vitro re-lease property of it. METHODS:Taking PLGA-PEG-PLGA as matrix and mannitol as viscosity modifiers,Methotrexate thermosen-sitive hydrogels were prepared. Using the absolute value of the deviation of gelation temperature between 35 ℃,its formulation was optimized by orthogonal test using the concentrations of PLGA-PEG-PLGA,methotrexate and mannitol as factors. The dialysis bag method was used to investigate accumulative release rate of Methotrexate thermosensitive hydrogels and methotrexate solution within 336 h in vitro. RESULTS:The optimal formulation was as PLGA-PEG-PLGA of 20%,methotrexate of 0.10% and mannitol of 0.10%;gelation temperature were 35.1,35.0,35.0℃. The average drug-loading rate was more than 90%. 12 d accumulative re-lease rate was more than 90%(r=3). Methotrexate solution has been substantially completely relased within 240 h. CONCLU-SIONS:Methotrexate thermosensitive hydrogels with sustained-release are prepared successfully,and the preparation technology is simple and practical.
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By developing a rapid gelation chitosan (CS) /β-glycerophosphate (β-GP) thermosensitive hydrogel containing Kuijiean, to decrease the loss of drug and confirm the capabilities of the drug delivery. Thermosensitive hydrogel was a carrier, gel time was chosen in this study as the index to investigate the effect of β-GP concentration, pH value, and temperature on the thermosensitive hydrogel by single factor experiments. The properties of the hydrogel were characterized regarding shape and surface morphology by using scaning electron microscopy (SEM); The chemical structure diversification of hydrogels upon gelation was charactered by FTIR spectrometer. By the experiments of the drug loaded thermosensitive hydrogel to deliver drug in vitro, the diversification of the capabilities of the drug delivery was evaluated. The temperature of Kuijiean thermosensitive hydrogel was (37.0 ± 4.5) ℃, by which the sol gel could transform into semi-solid gel at (6.00 ± 0.82) min, the drug release rate slowed down obviously, and the cumulative release rate was only (67.78 ± 0.35)% (n = 3) by 24 h, while the cumulative release rate of the equal quantity of raw material drug was (90.43 ± 0.62)% (n = 3) by 24 h. The release behavior was close to the Weibull model, the drug release mechanism was a double mechanism combining drug diffusion and gel erosion. It is true that achieves the transformation of Kuijiean from sol to semi-solid gel at 37.0 ℃. The CS/β-GP gel system allows the sustained release of the Kuijiean.
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OBJECTIVE: To synthesis chitosan/β-glycerophosphate (CS/β-GP) thermosensitive hydrogel containing multi-walled carbon nanotubes-polyethyleneimine (MWCNTs-PEI) complexes and to lay a foundation for further research of dual slow-release delivery system. METHODS: Chitosan thermosensitive hydrogel containing MWCNTs-PEI was prepared by MWCNTs-PEI dispersed to the chitosan thermosensitive hydrogel. As the indicator of the gelling time, the experiment studied the effect of β-GP concentration, pH, temperature and MWCNTs-PEI composite quality on the thermosensitive chitosan hydrogel, and then it was charactered by using transmission electron microscopy (SEM), infrared spectrometer(IR), and initially investigated in vivo compatibility. RESULTS: The dynamic rheology method investigated the gelling temperature were about 37.0°C. Within a certain range, the gelling time of thermosensitive chitosan hydrogel was shortened with the increase of concentration of β-GP, pH, temperature, and the quality of MWCNTs-PEI complexes, and they could be transformed into the hydrogel in vivo. The addition of MWCNTs-PEI complex didn't react chemically with the thermosensitive chitosan hydrogel and significantly make the holes of the chitosan thermosensitive hydrogel smaller by SEM and FT-IR, eventually leading to the swelling rate and the corrosional ratio decrease. CONCLUSION: Chitosan/β-glycerophosphate thermosensitive hydrogel containing amino-carbon nanotubes has a rapid gelation and good temperature-sensitivity, which can serve as a good double sustained-release carrier.
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OBJECTIVE: To synthesize magnetic thermosensitive hydrogel and study its heat effect under alternating magnetic field in vitro. METHODS: PLGA-PEG-PLGA triblock copolymer was synthesized by ring-opening polymerization of D, L-lactide and glycolide with PEG1500 in the presence of stannous iso caprylate. Magnetic thermosensitive hydrogel of different concentrations were prepared using different currents. The influences of the concentration of magnetic fluid and current of magnetic field on the heat effect were separately observed. RESULTS: The synthetized PLGA-PEG-PLGA triblock copolymer was excellently temperature sensitive. It retained the thermo-sensitivity of original hydrogel when the magnetic fluid was loaded. The 5, 10 and 20 min heating ability of magnetic fluid was positively linearly correlated with its concentration (r=0.9985, 0.9893 and 0.9711, respectively, n=3) and current of magnetic field (r=0.9948, 0.9977 and 0.9994, respectively, n=4). CONCLUSION: The magnetic thermosensitive hydrogel has excellent temperature sensitivity. When alternating magnetic field is applied, the temperature of the system can rise and reach above LCST of hydrogel. The temperature can be controlled by changing the concentration of magnetic fluid and the current of magnetic field. Copyright 2012 by the Chinese Pharmaceutical Association.
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Objective To prepare a sustained-delivery of paclitaxel-loaded thermosensitive hydrogel for the treatment of breast cancer by ultrasound-guided intratumoral injection,and probe the antitumor effect and mechanism of the new method. Methods Paclitaxel-loaded thermosensitive hydrogel was prepared. A total of 40 rats bearing subcutaneous breast tumor were randomized into 4 groups. Each group of rats were administered ultrasound-guided intratumoral injection of different agents as follows: salin, thermosensitive hydrogel, paclitaxel injection and paclitaxel-loaded thermosensitive hydrogel. The tumor nodules were scanned by high frequence ultrasound. The rats were sacrificed on the 14th day,and then the tumors were stripped to calculate the growth inhibitory rate. Histological examinations were undergone and RT-PCR was performed for the detection of bcl-2 and bax expression. Results Greater decrease in average tumor weight was found in paclitaxel-gel group [(16. 04 ± 2. 82)g], compared with that in paclitaxel group [(27.45 ±5.13)g, P ＜0. 05],and tumor growth inhibitory rate in the group was 62.77 %. In this group, blood flow signals reduction was detected on ultrasound and extensive necrosis was found in histological examination. In addition,down-regulation in bcl-2 mRNA expression and up-regulation in bax were found. Conclusions Ultrasound-guided percutaneous intratumoral injection of paclitaxel-loaded thermosensitive hydrogel may provide an effective method for breast tumor ablation therapy. The mechanism may be related to the inhibition of proliferation and induction of apoptosis.
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Objective To evaluate the clinical effects of scaling and root planning combined with application of the emodin thermosensitive hydrogel on periodontitis. Methods Forty patients with chronic periodontitis with a total of eighty teeth were included in the study.For each patient after scaling and root planning,the teeth on one side were assigned as the test group and treated with the emodin thermosensitive hydrogel in the pocket once a week for four weeks.The teeth on the other side were assigned as the control group.All the clinical parameters were recorded at the baseline,the 6th week and 12th week after the treatment. Results At the baseline,there was no difference in the clinical parameters between the test group and the control group(P＞0.05).A statistically significant improvement of all clinical parameters was observed in both groups 6w later(t = 39.06、62.76、20.50、8.05、158.32、31.45、46.53、8.43、8.08、8.03)(P＜0.01＝,and all clinical parameters of the test group were better than those of the control group,the differences were statistically significant(t = 31.50、27.91、3.92、7.38、20.09)(P＜0.01＝. Conclusion The emodin thermosensitive hydrogel could effectively control the symptoms of periodontitis.
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Objective To evaluate the effectiveness and feasibility of riein-loaded thermosenaitive hydrogel in percutaneous intratumoral injection for treatment of hepatic carcinoma. Methods BALB/c-nu mice were inoculated subcutaneously in the right flank with human liver cancer cell line HepG2. A total of 32 male mice bearing subcutaneous hepatic carcinoma (7-10mm in diameter) were randomized into 4 groups. Each group of mice were administered percutaneous intratumoral injection of different agents as follows: salin, thermosensitive hydrogel,ricin, ricin-loaded thermosensitive hydrogel. The tumor volume was totally measured 3 times by high frequency ultrasound once a week. One mouse of each group was sacrificed to perform tumor histopathological examination on 7th day, 14th day, respectively, and survival time of the remaining mice was recorded. Results After intratumoral therapy,tumor volume in ricin group was smaller than that of saline group on 7th day, 14th day and 21st day( P<0.01 ),and mice got a life-prolonging rate of 36.8%. In ricin-loaded thermosensitive hydrogel group,obvious necrosis occurred in tumors treated since 5th day, and the tumor almost regressed on 21st day. Histopathological assay showed serious necrosis with a large number of leucocyte infiltration in tumor. All the remaining mice treated with riein-loaded thermosensitive hydrogel survived at the end of experiment sans tumor recurrence. Conclusions Percutaneous intratutnoral injection of ricin-loaded thermosensitive hydrogel could completely ablate hepatic carcinoma,which may provide an effective and feasible method for tumor ablation therapy.
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OBJECTIVE: To prepare thermosensitive meloxicam hydrogel and establish its quality control method.METHODS: The hydrogel was prepared with poloxamer 407 and poloxamer 188 as base.The content of meloxicam in the thermosensitive gel was determined by UV spectrophotometry.RESULTS: The thermosensitive meloxicam hydrogel was yellowish or flavovirens in color,with its identification and tests all in conformity with the related specification stated in Chinese Pharmacopeia(2005 edition).The linear response range of meloxican was 1.956～19.56 mg?L-1(r=0.999 7).The average recovery was 98.42%(RSD=1.53%).CONCLUSION: The preparative technique is simple,and the quality of the preparation is controllable.
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Objective: To prepare a functional chitosan thermosensitive hydrogel for minocycline-HCl gelatin microspheres and observe its effects on repairing experimental rats gingivitis. Methods: Minocycline-HCl gelatin microspheres were prepared by using gelatin as core material and emulsion crosslinking method, then the latter was incorporated into the chitosan thermosensitive hydrogel. Established an experimental gingivitis model in SD rats and to observe the effect of hydrogel on gingivitis. Results: Microspheres thermosensitive hydrogel had obviously sustained effects on gingivitis. Results showed that GI,PD in experiment group were significantly improved. Conclusion: The chitosan thermosensitive hydrogel loading of minocycline-HCl gelatin microspheres have antiphlogistic effects on experimental rats gingivitis.
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Objective To evaluate the potential of chlorhexidine(Chx)-thermosensitive hydrogel as a local drug delivery system for periodontal treatment.Methods The release profiles of Chx from CS-HTCC/GP thermosensitive hydrogel in vitro were investigated.Moreover,the antibacterial activity of S-HTCC/GP-0.1%Chx thermosensitive hydrogel to oral representative pathogens - Porphyromonas gingivalis(P.gingivalis),Prevotella intermedia(P.intermedia) and Actinobacillus actinorn ycetemcornitans(A.actinom ycetemcomitans) was determined by inhibitory zone measurement.Results Chlorhexidine(Chx) released in vitro over 18 hours from the CS-HTCC/GP thermosensitive hydrogel in artificial saliva pH 6.8 which more effectively retarded the release of Chx.Three periodontal pathogens were susceptible to Chx thermosensitive hydrogel with the inhibitory zone diameters over the range of 12～14mm.Conclusion All results indicated that Chx thermosensitive hydrogel can be used as a local drug delivery system for periodontal treatment.