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The bone formation promoter recombinant human parathyroid hormone 1-34 [PTH (1-34)] has a short half-life and low bioavailability. In this study, we prepared a biodegradable and temperature-sensitive hyaluronic acid-poly-N-isopropyl acrylamide (AHA-g-PNIPAAm), and further investigated its effects of PTH (1-34) release and cell behavior as drug carrier. The structure of AHA-g-PNIPAAM was confirmed by hydrogen nuclear magnetic resonance spectroscopy and infrared spectroscopy. Next, PTH (1-34) loaded thermo-sensitive hydrogels were prepared by physical swelling method and their stability was investigated. The morphology of hydrogel was observed by scanning electron microscope. The minimum critical transition temperature and drug release behavior of hydrogels were investigated by ultraviolet spectrophotometry. The tetrazolium-based colorimetric assay (MTT assay) was used to investigate the toxicity and proliferation effects of PTH (1-34)-loaded thermo-sensitive hydrogel on mouse mononuclear macrophage RAW264.7 and mouse precranial osteoblasts MC3T3-E1. The effect of PTH (1-34)-loaded thermo-sensitive hydrogel on the differentiation of RAW264.7 was investigated by the tartrate-resistant acid phosphatase assay. The results showed that the PTH (1-34)-loaded thermo-sensitive hydrogel prepared in this study displayed regular three-dimensional honeycomb structure, and had good stability, thermo-sensitivity and sustained and controlled release properties, which could promote the proliferation of MC3T3-E1 cells more effectively and inhibit the differentiation of RAW264.7 into osteoclasts.
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PURPOSE: Aim of this study was to assess the safety and effectiveness of Keraheal-Allo® (Biosolution Co., Ltd., Korea) in patients with deep second-degree burn as a part of post marketing surveillance. METHODS: Seventy-five patients with deep second-degree burn were enrolled from April 2017 to October 2017. Keraheal-Allo, a thermos-sensitive hydrogel-type allogeneic keratinocytes, was applied to 90 deep second-degree burn sites of 75 patients. After application of Keraheal-Allo, the efficacy was assessed as the period of 100% re-epithelialization that was evaluated every time dressing was changed. RESULTS: The mean re-epithelialization period in the treated sites with KeraHeal-allo was 13.67±5.11 days. There was no severe adverse event. CONCLUSION: In conclusion, this thermo-sensitive hydrogel-type allogeneic keratinocytes have the clinical usefulness in terms of the safety, efficacy and ease of use.
Subject(s)
Humans , Bandages , Burns , Keratinocytes , Marketing , Re-EpithelializationABSTRACT
In order to explore the effect of abendazole sulfoxide-loaded thermo-sensitive hydrogel (ABZSO/PLGA-PEG-PL-GA) on alveolar hydatid cysts,the viable protoscoleces incubated in vitro with ABZSO/PLGA-PEG-PLGA (20,40,80 μg/mL),ABZSO (40 μg/mL),PLGA-PEG-PLGA and the blank control,respectively,and the viable protoscoleces were counted.The morphological of the alveolar hydatid cysts or protoscoleces in each group were observed by scanning electron microscop(SEM).After the rats infected with alveolar hydatid cysts having been treated,the sizes of the alveolar hydatid cysts were observed.When the alveolar hydatid cysts incubated in different drug group in 18 days,the percentage of viable protoscoleces in ABZSO/PLGA-PEG-PLGA (40μg/mL) group was lower than that of ABZSO (40 μg/mL) group.Results of SEM showed that the protoscoleces in the ABZSO/PLGA-PEG-PLGA (80 μg/mL) group were seriously damaged.The in vivo study demonstrated the anti-alveolar hydatid cysts efficacy of ABZSO/PLGA-PEG-PLGA (4 mg/mL) group was better than the other groups.The anti-alveolar hydatid cysts efficacy of ABZSO/PLGA-PEG-PLGA is evident.
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PURPOSE: Poloxamer 407 (P407) thermo-sensitive hydrogel formulations were developed to enhance the retention time in the urinary bladder after intravesical instillation. MATERIALS AND METHODS: P407 hydrogels (P407Gels) containing 0.2 w/w% fluorescein isothiocyanate dextran (FD, MW 4 kDa) as a fluorescent probe were prepared by the cold method with different concentrations of the polymer (20, 25, and 30 w/w%). The gel-forming capacities were characterized in terms of gelation temperature (G-Temp), gelation time (G-Time), and gel duration (G-Dur). Homogenous dispersion of the probe throughout the hydrogel was observed by using fluorescence microscopy. The in vitro bladder simulation model was established to evaluate the retention and drug release properties. P407Gels in the solution state were administered to nude mice via urinary instillation, and the in vivo retention behavior of P407Gels was visualized by using an in vivo imaging system (IVIS). RESULTS: P407Gels showed a thermo-reversible phase transition at 4℃ (refrigerated; sol) and 37℃ (body temperature; gel). The G-Temp, G-Time, and G-Dur of FD-free P407Gels were approximately 10℃–20℃, 12–30 seconds, and 12–35 hours, respectively, and were not altered by the addition of FD. Fluorescence imaging showed that FD was spread homogenously in the gelled P407 solution. In a bladder simulation model, even after repeated periodic filling-emptying cycles, the hydrogel formulation displayed excellent retention with continuous release of the probe over 8 hours. The FD release from P407Gels and the erosion of the gel, both of which followed zero-order kinetics, had a linear relationship (r²=0.988). IVIS demonstrated that the intravesical retention time of P407Gels was over 4 hours, which was longer than that of the FD solution ( < 1 hour), even though periodic urination occurred in the mice. CONCLUSIONS: FD release from P407Gels was erosion-controlled. P407Gels represent a promising system to enhance intravesical retention with extended drug delivery.
Subject(s)
Animals , Mice , Administration, Intravesical , Dextrans , Drug Liberation , Fluorescein , Hydrogels , Hydrogels , In Vitro Techniques , Kinetics , Methods , Mice, Nude , Microscopy, Fluorescence , Optical Imaging , Phase Transition , Poloxamer , Polymers , Urinary Bladder , UrinationABSTRACT
Objective To evaluate the therapeutic effect of PLGA-PEG-PLGA-5-fluorouracil temperature-sensitive hydrogel interstitial chemotherapy for pancreatic cancer by using endoscopic ultrasonography.Methods PLGA-PEG-PLGA-5-fluorouracil temperature-sensitive hydrogel in vitro release experiments were performed in the following procedures:determination of lixivium drug concentration and calculation of its emission.Fifty nude mice with the pancreatic cancer cell line SW1990 were randomly divided into 5 groups,10 in each group.Group A was intratumorally injected with PLGA-PEG-PLGA-5-fluorouracil temperature-sensitive hydrogel at 4mg/kg ; group B with PLGA-PEG-PLGA-5-fluorouracil temperature-sensitive hydrogel at lmg/kg; Group C was intratumorally injected with 5-fluorouracil at 4 mg/kg ; Group D with PLGAPEG-PLGA matrix at 4mg/kg ;and group E was the control group.Tumor growth and audio-visual images of the nude mice tumor nodules were observed before administration,and 3,7,10,14 days after.Tumor growth curve was also drawn.Animals were sacrificed at 14 days Tumors were weighed to calculate the inhibitory rate and stained for pathological study.Results 1,3,5,8,10,and 14-day release of 5-fluorouracil temperature-sensitive hydrogel were 21.6％,33.8 ％,44.3％,63.6％,76.3％ and 91.8％.Tumor sizes of group A and group B were significantly different from those of other groups (P ＜ 0.05).Ultrasound endoscopic image characteristics were correlated with pathological findings.Conclusion PLGA-PEG-PLGA-5-fluorouracil temperature-sensitive hydrogel is able to release for 14 days in vitro,which constantly inhibits human pancreatic cancer cell line SW1990.Intratumoral injection of the agent can significantly inhibit the growth of pancreatic cancer of nude mice.Additionally,gelatinous preparations fixes better than liquid and is of clinical value.Therefore,monitoring temperature-sensitive 5-fluorouracil hydrogel interstitial chemotherapy for pancreatic cancer with endoscopic ultrasound is convenient and safe.
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OBJECTIVE: To prepare thermo-sensitive ornidazole hydrogel and establish its quality control method.METHODS: Thermo-sensitive ornidazole hydrogel was prepared with ornidazole as chief constituent using poloxamer 407 and poloxamer 188 as base.The content of ornidazole in the hydrogel was determined by ultraviolet spectrophotometry.RESULTS: The preparation was white or yellowish semisolid gel,and its test results were up to the related standard specified in Chinese Pharmacopeia(2005 Edition).The linear range of ornidazole was 3.98～43.77 mg?L-1(r=0.999 8),and its mean recovery was 98.52%(RSD=1.1%).CONCLUSION: The preparation is simple and feasible in preparation process,and the quality of the preparation is stable and controllable.