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@#Diabetic macular edema(DME)is the foremost cause of vision impairment and even blindness in patients with diabetes mellitus. Nowadays, the approach in the treatment of DME involves laser photocoagulation, intravitreal injections of anti-VEGF agents or triamcinolone acetonide. However, they still have some limitations. In recent years, dexamethasone intravitreal implant, as a new treatment option, has brought therapeutic hope to DME patients who have poor response to other methods. Meanwhile, it has the advantages of good clinical efficacy, long duration, acceptable safety and good patient tolerability. In this paper, the research advances in dexamethasone intravitreal implant for DME are described.
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Objective: To construct bone morphogenetic protein 2 (BMP-2) gelatin/chitosan hydrogel sustained-release system, co-implant with induced pluripotent stem cells (iPS) derived mesenchymal stem cells (MSCs) to hydroxyapatite (HA)/zirconium dioxide (ZrO 2) bio porous ceramic foam, co-culture in vitro, and to explore the effect of sustained-release system on osteogenic differentiation of iPS-MSCs. Methods: BMP-2 gelatin/chitosan hydrogel microspheres were prepared by water-in-oil solution. Drug encapsulation efficiency, drug loading, and in vitro sustained release rate of the microspheres were tested. HA/ZrO 2 bio porous ceramic foam composite iPS-MSCs and BMP-2 gelatin/chitosan hydrogel sustained release system co-culture system was established as experimental group, and cell scaffold complex without BMP-2 composite gelatin/chitosan hydrogel sustained release system as control group. After 3, 7, 10, and 14 days of co-culture in the two groups, ALP secretion of cells was detected; gene expression levels of core binding factor alpha 1 (Cbfa1), collagen type Ⅰ, and Osterix (OSX) were detected by RT-PCR; the expression of collagen type Ⅰ was observed by immunohistochemical staining at 14 days of culture; and cell creep and adhesion were observed by scanning electron microscopy. Results: BMP-2 gelatin/chitosan hydrogel sustained-release system had better drug encapsulation efficiency and drug loading, and could prolong the activity time of BMP-2. The secretion of ALP and the relative expression of Cbfa1, collagen type Ⅰ, and OSX genes in the experimental group were significantly higher than those in the control group at different time points in the in vitro co-culture system ( P<0.05). Immunohistochemical staining showed that the amount of fluorescence in the experimental group was significantly more than that in the control group, i.e. the expression level of collagen type Ⅰ was higher than that in the control group. The cells could be more evenly distributed on the materials, and the cell morphology was good. Scanning electron microscopy showed that the sustained-release system could adhere to cells well. Conclusion: iPS-MSCs have the ability of osteogenic differentiation, which is significantly enhanced by BMP-2 gelatin/chitosan hydrogel sustained-release system. The combination of iPS-MSCs and sustained-release system can adhere to the materials well, and the cell activity is better.
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OBJECTIVE:To prepare Hyaluronic acid-methyl collagen-terpolymer (HEMA-MMA-MAA)/Doxorubicin com-pound membranes-loaded tantalum stent,and to optimize the formulation. METHODS:Electrostatic self-assembly reaction was ad-opted to prepare compound membranes using metal tantalum stent as carrier,hyaluronic acid,methyl collagen and terpolymer as ex-cipients. With 1 and 30 d accumulative release rate as index,orthogonal test was used to optimize mass concentrations of hyaluron-ic acid,methyl collagen and terpolymer,and validated. The drug release behavior in vitro were investigated. RESULTS:The opti-mal formulation was as hyaluronic acid 1 mg/ml,methyl collagen 4.5 mg/ml and terpolymer 100 mg/ml. 1 and 30 d accumulative release rates of prepared tantalum stent were 7.57%(RSD=2.3%,n=3) and 84.14%(RSD=2.1%,n=3),respectively. 20 d later,dissolution rate approximated to zero level rate of drug release. CONCLUSIONS:Hyaluronic acid-methyl collagen-terpoly-mer/Doxorubicin compound membranes-loaded tantalum stent with sustained-release property is prepared successfully.
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Now a days as very few drugs are coming out of research and development and already existing drugs are suffering the problem of resistance due to their irrational use specifically in case of drugs like antibiotics. Hence, change in the operation is a suitable and optimized way to make the some drug more effective by slight alteration in the drug delivery.
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10.3969/j.issn.2095-4344.2013.25.019
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PURPOSE: The purpose of this study was to evaluate the effect of two sustained release systems (Pluronic F-127 gel and Fibrin glue) on the diffusion of dexamethasone across the human sclera. METHODS: Scleral sections excised from moist-chamber-stored human globes were mounted in a perfusion chamber that can create transscleral pressure. In the sustained release study, sample (100 muL) of 3H-dexamethasone in Pluronic F-127 gel or Fibrin glue was added to the episcleral side of the tissue, while BSS plusR was perfused across the uveal side at an transscleral pressure of 15 mmHg. Perfusate fractions were collected and measured using scintillation spectrometry and scleral permeability was calculated. RESULTS: The apparent permeability constants of the human sclera to 3H-dexamethasone in BSS plus(R) (the control value), Pluronic F-127 gel, and Fibrin glue were 1.15+/-0.11x10(-5) cm/s (n=5), 1.49+/-0.33x10-6 cm/s (n=5), and 7.32+/-0.98x10(-6) cm/s (n=7), respectively. The permeability values of Pluronic F-127 gel and Fibrin glue were relatively lower than the control value. Pluronic F-127 gel and Fibrin glue showed a uniform sustained release characteristic during a 24-hour period. The cumulative release rates of dexamethasone through the human sclera from BSS plus(R) (the control value), Pluronic F-127 gel, and Fibrin glue were 84.0+/-1.5% (n=5), 29.3+/-5.8% (n=5), and 61.5+/-5.9% (n=4) at 20 hours, respectively. There were significant differences in the human scleral permeability constants and cumulative release rates among the three vehicles (p<0.0001). CONCLUSIONS: Pluronic F-127 gel and Fibrin glue provided a slow, uniform sustained release during a 24- hour period. This study established a strong possibility of the new transscleral drug delivery in vitro using the sustained release systems of Pluronic F-127 gel and Fibrin glue. This may be a good experimental tool in the future development of a practical drug delivery system across the sclera for the treatment of a variety of chorioretinal disorders.