共查询到20条相似文献,搜索用时 15 毫秒
1.
《Cell cycle (Georgetown, Tex.)》2013,12(7):854-856
Specifically and effectively directing a therapeutic gene to its intended site of action is a critical issue for translation of basic genomics to clinical gene therapy. Delivering gene therapy vectors to specific cells or tissues through intravenous injection is the most desirable method for this purpose. In 2001, we reported successful targeted gene transduction in vitro utilizing both oncoretroviral and lentiviral vectors pseudotyped with a chimeric Sindbis virus envelope (ZZ SINDBIS). However, these pseudotypes mediated non-specific gene transduction to liver and spleen in vivo. To address this problem we generated the modified ZZ SINDBIS (termed m168) with significantly less non-specific infectivity. To investigate the ability of m168 pseudotyped lentiviral vector to mediate targeted gene transduction in vivo, we utilized a metastatic tumor model by using mouse melanoma cells engineered to express human P-glycoprotein. We administered the m168 pseudotyped vector conjugated with anti-P-glycoprotein antibody into the mice intravenously to target metastatic melanoma. The m168 pseudotyped vector selectively infected metastatic melanoma cells demonstrating successful targeted gene transduction in vivo. Targeting technology based upon m168 can be further modified for application not only to cancer but also potentially to genetic, neurologic, infectious and immune diseases, thereby expanding the future application of gene therapy. 相似文献
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Jojoba oil-based emulgel formulations were prepared using different concentrations of various gelling agents, such as hydroxypropyl methylcellulose (HPMC) and Carbopol 934 P and combination of both. The prepared emulgels were physically evaluated for their stability after temperature cycle test, centrifugation and long-term shelf storage for 1 year at room temperature. The in vitro release at 37°C was studied to define the effect of the concentration and type of the gelling agent. A comparison between the formulated emulgels and two commercially available products, Candistan® and Canesten® creams, was carried out to judge their efficacy and stability. The prepared emulgels exhibited non-Newtonian shear thinning behavior with little or no thixotropy. Four emulgels showed excellent stability as they demonstrated consistent rheological model under different treatment conditions. The in vitro release test showed variation in the extent of percent drug released. The drug release from the commercial preparation was lower than some of the prepared emulgel formulae. One formula containing combination of the two gelling agents (HPMC and Carbopol 934 P), showed excellent stability and high extent of clotrimazole release was microbiologically evaluated against Candida albicans using cylinder and plate method. The selected formula showed superior antimycotic activity compared to the commercially available formulation. Further in vivo animal studies for the obtained stable formula is recommended. 相似文献
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Karine Fabio Kieran Curley Joseph Guarneri Benoit Adamo Brendan Laurenzi Marshall Grant Robin Offord Kelly Kraft Andrea Leone-Bay 《AAPS PharmSciTech》2015,16(6):1299-1306
In this work, heat stable dry powders of oxytocin (OT) suitable for delivery by oral inhalation were prepared. The OT dry powders were prepared by spray drying using excipients chosen to promote OT stability including trehalose, isoleucine, polyvinylpyrrolidone, citrate (sodium citrate and citric acid), and zinc salts (zinc chloride and zinc citrate). Characterization by laser diffraction indicated that the OT dry powders had a median particle size of 2 μm, making them suitable for delivery by inhalation. Aerodynamic performance upon discharge from proprietary dry powder inhalers was evaluated by Andersen cascade impaction (ACI) and in an anatomically correct airway (ACA) model, and confirmed that the powders had excellent aerodynamic performance, with respirable fractions up to 77% (ACI, 30 L/min). Physicochemical characterization demonstrated that the powders were amorphous (X-ray diffraction) with high glass transition temperature (modulated differential scanning calorimetry, MDSC), suggesting the potential for stabilization of the OT in a glassy amorphous matrix. OT assay and impurity profile were conducted by reverse phase HPLC and liquid chromatography-mass spectrometry (LC-MS) after storage up to 32 weeks at 40°C/75%RH. Analysis demonstrated that OT dry powders containing a mixture of citrate and zinc salts retained more than 90% of initial assay after 32 weeks storage and showed significant reduction in dimers and trisulfide formation (up to threefold reduction compared to control).
Electronic supplementary material
The online version of this article (doi:10.1208/s12249-015-0314-0) contains supplementary material, which is available to authorized users.KEY WORDS: dry powder, oral inhalation, oxytocin, peptide delivery, postpartum hemorrhage 相似文献4.
目的:优化大肠杆菌菌蜕装载质粒的效率,并将装载质粒的菌蜕转染抗原提呈细胞,以提高核酸疫苗的递送水平。方法:将质粒pHH43转化大肠杆菌DH5α,制备大肠杆菌菌蜕;优化菌蜕装载质粒时菌蜕、质粒和膜囊的比例,获得更高的装载效率,通过扫描及透射电镜、流式细胞术观察其形态变化及装载效率;将装载质粒的菌蜕与抗原提呈细胞——巨噬细胞RAW264.7和树突状细胞DC2.4共孵育,观察吞噬效果。结果:优化了大肠杆菌菌蜕装载质粒的效率,当菌蜕、质粒、膜囊的比例为7∶10∶4时效率达到最佳,装载DNA效率达98%以上;抗原提呈细胞吞噬装载了质粒的菌蜕,效率达100%。结论:大肠杆菌菌蜕可高效装载核酸疫苗,且高效被抗原提呈细胞捕获,有助于提高核酸疫苗的递送和免疫效果的提高。 相似文献
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Patil Saurabh Gupta Kritika Pandit Ashish Desai Bhushan Gschliesser Siegfried Dandekar Prajakta Jain Ratnesh 《International journal of peptide research and therapeutics》2021,27(4):2831-2844
International Journal of Peptide Research and Therapeutics - The development of peptide-based formulations presents numerous challenges to the formulator due to their complexity, delicate structure... 相似文献
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目的:基因方法治疗癌症近年来取得了很大的突破,因此基因载体的构建显得尤为重要.其中纳米基因载体合成简单,成本低廉,并能够包裹、浓缩、保护核苷酸使其免受核酸酶降解,因此纳米材料广泛地应用于基因输送.我们拟开展聚乙烯亚胺-纳米金基因载体的制备及其表征.方法:采用层层包裹技术制备基因载体,首先通过柠檬酸钠还原法制备纳米金颗粒后,应用11-巯基十一烷酸对金颗粒进行修饰,使其表面带有羧基,然后进一步将带有氨基的低分子量聚乙烯亚胺与羧基进行连接.应用动态光散射(DLS),紫外可见光谱(UV)和透射电子显微镜(TEM)对构建的纳米基因载体进行表征.结果:成功制备了聚乙烯亚胺-纳米金基因载体,检测表明每一步制备出的产物纳米尺寸在20-30nm之间,液体均匀稳定,分散系数(PDI)在0.2以下,Zeta电位测定表明,每步的产物电荷变化与外层包裹的反应物有关.尽管金颗粒外层包裹聚乙烯亚胺,但是总体上纳米载体尺寸没有发生太大的变化,TEM检测表明每一步形成了均匀的、单分散的、球状的纳米颗粒.结论:我们通过层层包裹技术成功制备了聚乙烯亚胺-纳米金基因载体,在进一步开展的生物活性的检测中,希望通过纳米载体的携带作用,将基因转染进靶细胞,从而检测相关基因对靶细胞的沉默作用,提高基因药物的应用,为开发新型基因药物提供基础. 相似文献
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基因疫苗具有很多独特的优点,已经成为疫苗研究领域的热点。但由于其免疫原性相对较弱,限制了基因疫苗的广泛应用。人们一直在寻求一种理想的基因疫苗运送系统,它不仅能将基因疫苗导入体内,还能提高基因疫苗的免疫原性,诱导机体产生持续高水平的免疫应答反应。 相似文献
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Haznar-Garbacz D Garbacz G Eisenächer F Klein S Weitschies W 《AAPS PharmSciTech》2011,12(4):1183-1185
A novel oral drug delivery system for the controlled release of liquid drugs, drug solutions, and semisolid drug preparations
is presented that is utilizing the constant vapor pressure of liquefied gas. The system is equipped with a capillary as an
element determining the drug delivery rate and contains a liquefied propellant with a suitable boiling point below human body
temperature. In the dissolution studies, polyacrylate gels of different viscosities containing paracetamol as model drug were
used. Zero-order release kinetics was obtained. The release rates were dependent on the gel viscosity. Besides, by gel viscosity,
the drug release rates could also be modified by changing the propellant type and the capillary parameters such as length
or diameter. Accordingly, the new system enables a wide range of drug delivery kinetics which can be modified in a case-by-case
basis in order to match the desired drug delivery characteristics. 相似文献
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Georgeta Coneac Vicen?iu Vlaia Ioana Olariu Ana Maria Mu? Dan Florin Anghel Cornelia Ilie C?lin Popoiu Dumitru Lupuleasa Lavinia Vlaia 《AAPS PharmSciTech》2015,16(4):889-904
The aim of the present investigation was to develop and evaluate microemulsion-loaded hydrogels (MEHs) for the topical delivery of fluconazole (FZ). The solubility of FZ in oils, surfactants and cosurfactants was evaluated to identify the components of the microemulsion. The pseudo-ternary phase diagrams were constructed using the novel phase diagram by micro-plate dilution method. Carbopol EDT 2020 was used to convert FZ-loaded microemulsions into gel form without affecting their structure. The selected microemulsions were assessed for globule size, zeta potential and polidispersity index. Besides this, the microemulsion-loaded hydrogel (MEH) formulations were evaluated for drug content, pH, rheological properties and in vitro drug release through synthetic membrane and excised pig ear skin in comparison with a conventional hydrogel. The optimised MEH FZ formulations consisting of FZ 2%, Transcutol P 11.5% and 11%, respectively, as oil phase, Lansurf SML 20-propyleneglycol 52% and 50%, respectively, as surfactant–cosurfactant (2:1), Carbopol EDT 2020 1.5% as gelling agent and water 34.5% and 37%, respectively, showed highest flux values and high release rate values, and furthermore, they had low surfactant content. The in vitro FZ permeation through synthetic membrane and excised pig ear skin from the studied MEHs was best described by the zero-order and first-order models. Finally, the optimised MEH FZ formulations showed similar or slightly higher antifungal activity as compared to that of conventional hydrogel and Nizoral® cream, respectively. The results suggest the potential use of developed MEHs as vehicles for topical delivery of FZ, encouraging further in vitro and in vivo evaluation.KEY WORDS: fluconazole, in vitro skin permeation, microemulsion, microemulsion-loaded hydrogel, topical 相似文献
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目的:本研究诣在对壳聚糖进行修饰,以解决其水溶性问题和基因释放困难的问题。方法:本研究通过2,3-环氧丙基三甲基氯化铵和N-乙酰-L-半胱氨酸对壳聚糖进行修饰,得到巯基化壳聚糖季铵盐(TMC-SH),使其在生理条件下带正电并含有一定量的游离巯基。以TMC-SH为基因载体,形成基因复合物。通过琼脂糖凝胶电泳考察其稳定性,并测定其粒径和ζ-电位。通过DTT条件下的粒径测定,考察基因复合物的还原响应性。结果:核磁结果表明合成TMC-SH的季铵盐取代度为22%,游离巯基-SH含量为79.22μmol/g;琼脂糖凝胶电泳结果表明以TMC-SH为载体形成的二硫键交联的基因复合物TMC-SS/p DNA具有较好的稳定性;而且,二硫键交联以后基因复合物粒径较小,结构更为密实;在还原条件下粒径变大,表明二硫键交联的基因复合物变得疏松,说明其粒径具有还原响应性。结论:对壳聚糖进行低取代度的季铵盐修饰和一定量的巯基化修饰后,其具有较好的包载p DNA能力和还原响应性的基因释放能力。 相似文献
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Lipid nanoparticles based on solid matrix have emerged as potential drug carriers to improve gastrointestinal (GI) absorption and oral bioavailability of several drugs, especially lipophilic compounds. These formulations may also be used for sustained drug release. Solid lipid nanoparticle (SLN) and the newer generation lipid nanoparticle, nanostructured lipid carrier (NLC), have been studied for their capability as oral drug carriers. Biodegradable, biocompatible, and physiological lipids are generally used to prepare these nanoparticles. Hence, toxicity problems related with the polymeric nanoparticles can be minimized. Furthermore, stability of the formulations might increase than other liquid nano-carriers due to the solid matrix of these lipid nanoparticles. These nanoparticles can be produced by different formulation techniques. Scaling up of the production process from lab scale to industrial scale can be easily achieved. Reasonably high drug encapsulation efficiency of the nanoparticles was documented. Oral absorption and bioavailability of several drugs were improved after oral administration of the drug-loaded SLNs or NLCs. In this review, pros and cons, different formulation and characterization techniques, drug incorporation models, GI absorption and oral bioavailability enhancement mechanisms, stability and storage condition of the formulations, and recent advances in oral delivery of the lipid nanoparticles based on solid matrix will be discussed. 相似文献
15.
Haghighat Vakilian Eduardo Andres Rojas Lida Habibi Rezaei Mehrdad Behmanesh 《Reports of Biochemistry & Molecular Biology》2020,9(3):297
Background:One of the major challenges in gene therapy is producing gene carriers that possess high transfection efficiency and low cytotoxicity (1). To achieve this purpose, crystal nanocellulose (CNC) -based nanoparticles grafted with polyethylenimine (PEI) have been developed as an alternative to traditional viral vectors to eliminate potential toxicity and immunogenicity.Methods:In this study, CNC-PEI10kDa (CNCP) nanoparticles were synthetized and their transfection efficiency was evaluated and compared with linear cationic PEI10kDa (PEI) polymer in HEK293T (HEK) cells. Synthetized nanoparticles were characterized with AFM, FTIR, DLS, and gel retardation assays. In-vitro gene delivery efficiency by nano-complexes and their effects on cell viability were determined with fluorescent microscopy and flow cytometry.Results:Prepared CNC was oxidized with sodium periodate and its surface cationized with linear PEI. The new CNCP nano-complex showed different transfection efficiencies at different nanoparticle/plasmid ratios, which were greater than those of PEI polymer. CNPC and Lipofectamine were similar in their transfection efficiencies and effect on cell viability after transfection.Conclusion:CNCP nanoparticles are appropriate candidates for gene delivery. This result highlights CNC as an attractive biomaterial and demonstrates how its different cationized forms may be applied in designing gene delivery systems.Key Words: Crystal Nanocellulose, Gene transfection, Nanoparticle, Nano-complex 相似文献
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Maria Luisa Agüera Alejandro Martin-Malo Maria Antonia Alvarez-Lara Victoria Eugenia Garcia-Montemayor Petra Canton Sagrario Soriano Pedro Aljama 《PloS one》2015,10(8)
Aims
The appropriate use of intravenous (IV) iron is essential to minimise the requirements for erythropoiesis-stimulating agents (ESAs). The clinical efficacy of generic IV iron compared to the original formulation is controversial. We evaluated the changes that were induced after switching from a generic IV iron to an original formulation in a stable, prevalent haemodialysis (HD) population.Methods
A total of 342 patients were included, and the follow-up period was 56 weeks for each formulation. Anaemia parameters and doses of ESA and IV iron were prospectively recorded before and after the switch from generic to original IV iron.Results
To maintain the same haemoglobin (Hb) levels after switching from the generic to the original formulation, the requirements for IV iron doses were reduced by 34.3% (from 52.8±33.9 to 34.7±31.8mg/week, p<0.001), and the ESA doses were also decreased by 12.5% (from 30.6±23.6 to 27±21μg/week, p<0.001). The erythropoietin resistance index declined from 8.4±7.7 to 7.4±6.7 IU/kg/week/g/dl after the switch from the generic to the original drug (p = 0.001). After the switch, the transferrin saturation ratio (TSAT) and serum ferritin levels rose by 6.8%(p<0.001) and 12.4%(p = 0.001), respectively. The mortality rate was similar for both periods.Conclusions
The iron and ESA requirements are lower with the original IV iron compared to the generic drug. In addition, the uses of the original formulation results in higher ferritin and TSAT levels despite the lower dose of IV iron. Further studies are necessary to analyse the adverse effects of higher IV iron dosages. 相似文献17.
Orodispersible film (ODF) technology offers new possibilities for drug delivery by providing the advantages of oral delivery
coupled with the enhanced onset of action and convenience to special patient categories such as pediatrics and geriatrics.
In this study, mosapride (MOS) was formulated in an ODF preparation that can be used for treatment of patients who suffer
from gastrointestinal disorders, especially difficulty in swallowing due to gastroesophageal reflux disease. Poloxamer 188
was used to solubilize MOS to allow its incorporation into the film matrix. The films were prepared by solvent-casting method
using different polymer ratios of maltodextrin and hydroxypropyl methylcellulose and plasticizer levels of glycerol and propylene
glycol. A D-optimal design was utilized to study the effect of polymer ratio, plasticizer type, and level on film mechanical
properties, disintegration time, and dissolution rate. Statistical analysis of the experimental design showed that the increase
of maltodextrin fraction and plasticizer level conferred optimum attributes to the prepared films in terms of film elasticity,
film disintegration time, and MOS release rate. The ODF formulations were further tested for moisture sorption capacity, with
formulations containing a higher ratio of maltodextrin and percent plasticizer showing more moisture uptake. The optimum film
composition was also tested in vivo for film palatability and disintegration time. An optimized mosapride orodispersible film formulation was achieved that could
be of benefit to patients suffering from gastrointestinal disorders. 相似文献
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Soad A. Yehia Ahmed H. Elshafeey Ibrahim Sayed Ahmed H. Shehata 《AAPS PharmSciTech》2009,10(1):147-157
The purpose of this study was to formulate budesonide (BUD) compression-coated tablets for colonic specific delivery. Pectin
and guar gum were used as enzyme-dependent polymers. For comparison purposes, both pH- and time-dependent polymers were also
tried. In vitro release studies were carried out at different pH (1.2, 6.8, and 7.4). Therapeutic efficacy of the prepared tablets compared
to commercially available capsules and enema were evaluated in trinitrobenzenesulfonic acid-induced rabbit colitis model.
In pH-dependent polymers, Eudragit (EUD) S100/EUD L100 (1:1) released 45.58% in the target area (colon). For time-dependent
polymers, decreasing cellulose acetate butyrate (CAB) ratio increased the release in both pH 6.8 and 7.4 till it reached 40.58%
and 93.65%, respectively, for 25% CAB. In enzyme-dependent polymers, increasing pectin ratio to 75% retarded the release (4.59%
in pH 6.8 and 54.45% in pH 7.4) which was significantly enhanced to 99.31% using pectinolytic enzyme. Formula F14 coated with
75% pectin significantly reduced the inflammatory cells in the connective tissue core of the colon of the treated group and
significantly decreased myeloperoxidase activity (3.90 U/g tissue weight). This study proved that BUD compression-coated with
75% pectin may be beneficial in the treatment of inflammatory bowel disease. 相似文献
19.
A. V. Ulasov Y. V. Khramtsov T. N. Lupanova A. D. Tsvetkova A. A. Rosenkranz T. A. Slastnikova G. P. Georgiev A. S. Sobolev 《Doklady. Biochemistry and biophysics》2018,479(1):62-65
We studied the possibility of optimizing modular nanotransporters (MNTs) for the intracellular delivery of antibody fragments into the nuclei of cells of a specified type. Basic MNT with a reduced size retaining the desired functions was obtained, and the principal possibility of obtaining an MNT carrying an antibody fragment by microbiological synthesis was shown. 相似文献
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Many gene delivery methods have been used to transduce or transfect bone marrow-derived dendritic cells (BMDCs) for genetic
engineered DC vaccine research. The present study, for the first time, evaluated the efficiencies of four methods (lipofection,
DNA electroporation, recombinant adeno-associated virus type 2 (rAAV2) transduction, and recombinant lentivirus (rLV) transduction)
using EGFP as a report gene in the same BMDC culture system. Our data demonstrate that rLV transduction is the most effective
method; both lipofection and DNA electroporation transfect BMDCs at lower efficiencies; rAAV2 can hardly transduce BMDCs.
Furthermore, our results, for the first time, demonstrate that rLV transduction efficiency on BMDCs can be improved significantly
by co-centrifugation and repeated transduction. 相似文献