Colon-Targeted Therapy of Tacrolimus (FK506) in the Treatment of Experimentally Induced Colitis

Pharmacology ◽  
2020 ◽  
Vol 105 (9-10) ◽  
pp. 541-549 ◽  
Author(s):  
Ahmed S. Ali ◽  
Abid A. Altayari ◽  
Lateef M. Khan ◽  
Sameer E. Alharthi ◽  
Osama A. Ahmed ◽  
...  
Keyword(s):  
Drug Release ◽  
Targeted Delivery ◽  
Intestinal Inflammation ◽  
Rescue Therapy ◽  
Immunosuppressive Agent ◽  
Water Emulsion ◽  
Distribution Study ◽  
In Vivo Distribution ◽  
Oil In Water Emulsion

<b><i>Background/Aims:</i></b> Inflammatory bowel disease is a chronic or remitting/relapsing intestinal inflammation, which comprises Crohn’s disease and ulcerative colitis (UC). Severe UC is a life-threatening condition that requires corticosteroids (CS) as a first-line rescue therapy. Some patients are refractory to CS and may require alternative immunosuppressive therapy. Oral tacrolimus (FK506), an immunosuppressive agent, has been reported to be effective in the management of severe refractory UC, but it can cause serious adverse effects. This work aims to study the effect of tacrolimus delivered by a colon-targeted delivery system (CTDS) in a dextran sulfate sodium (DSS)-induced animal model of colitis. <b><i>Materials and Methods:</i></b> We developed and evaluated an oral CTDS of tacrolimus (FK506) loaded pH-dependent polymeric microspheres, composed of Eudragit® S100 as a pH-sensitive polymer using the oil-in-water emulsion method. The physicochemical properties and drug release profiles of these microparticles in gastrointestinal tract (GIT) conditions were examined. A DSS-induced colitis rat model was used to evaluate the potential remedial and in vivo distribution of microspheres. <b><i>Results:</i></b> The pH-microspheres prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. The in vivo distribution study in the rat GIT demonstrated that pH-microspheres were successfully delivered to the inflamed colon. Moreover, it also demonstrated a significant decrease of disease activity and expression of proinflammatory cytokines, such as tumor necrosis factor α, interleukin-1β (IL-1β), and IL-6, and minimized the histological and morphometric changes. <b><i>Conclusion:</i></b> The results confirmed the efficacy of tacrolimus (FK506) CTDs in the management of DSS-induced colitis.

scholarly journals Berberine-Coated Biomimetic Composite Microspheres for Simultaneously Hemostatic and Antibacterial Performance

Polymers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 360
Author(s):  
Xiaojian Zhang ◽  
Kaili Dai ◽  
Chenyu Liu ◽  
Haofeng Hu ◽  
Fulin Luo ◽  
...  
Keyword(s):  
In Vitro Test ◽  
Water Emulsion ◽  
Biomedical Material ◽  
Composite Microspheres ◽  
Antibacterial Performance ◽  
New Strategy ◽  
Oil In Water Emulsion ◽  
Hemostatic Powder

Biomimetic microspheres containing alginate/carboxymethylcellulose/gelatin and coated with 0%, 1%, 3%, and 6% berberine (BACG, BACG-1B, BACG-3B, BACG-6B) were prepared by the oil-in-water emulsion method combined with spray drying. Through a series of physicochemical parameters and determination of hemostatic properties in vitro and in vivo, the results indicated that BACG and BACG-Bs were effective in inducing platelet adhesion/aggregation and promoting the hemostatic potential due to their biomimetic structure and rough surface. In addition, BACG-6B with high berberine proportion presented better hemostatic performance compared with the commercial hemostatic agent compound microporous polysaccharide hemostatic powder (CMPHP). BACG-6B also showed strong antibacterial activity in the in vitro test. The hemolysis test and cytotoxicity evaluation further revealed that the novel composite biomaterials have good hemocompatibility and biocompatibility. Thus, BACG-6B provides a new strategy for developing a due-functional (hemostat/antibacterial) biomedical material, which may have broad and promising applications in the future.

scholarly journals Development and Permeability Testing of Self-Emulsifying Atorvastatin Calcium Pellets and Tablets of Compressed Pellets

Processes ◽  
2019 ◽  
Vol 7 (6) ◽  
pp. 365 ◽  
Author(s):  
Mine Diril ◽  
Yesim Karasulu ◽  
Miltiadis Toskas ◽  
Ioannis Nikolakakis
Keyword(s):  
Drug Release ◽  
Drug Transport ◽  
Tween 20 ◽  
Water Emulsion ◽  
Atorvastatin Calcium ◽  
Solubility Improvement ◽  
Pellet Surface ◽  
Oil In Water ◽  
Presystemic Metabolism ◽  
Oil In Water Emulsion

Self-emulsifying pellets (SEPs) of Atorvastatin Calcium (AtrCa) were developed and processed into tablets (SETs). Self-emulsifying drug delivery system (SEDDS) composed of oleic acid, Tween 20, Span 80 and N-Methyl-2-pyrolidone gave great solubility improvement and was used as oil in water emulsion for the preparation of SEPs. Due to the high 60% w/w SEDDS content required to achieve a therapeutic dose in the final tablet form, sonication was necessary to improve fluidity and stability. Colloidal silicon dioxide (CSD) and microcrystalline cellulose (MCC) were the solids in the pellet formulation employed at a ratio 7:3, which enabled production of pellets with high SEDDS content and acceptable friability as well. Emulsions were characterized physico-chemically, SEPs for physical properties and reconstitution, and tablets of compressed pellets for mechanical strength, disintegration into pellets and drug release. SEPs compressed with 30% MCC at 60 MPa gave tablets of adequate strength that disintegrated rapidly into pellets within 1 min. Emulsion reconstitution took longer than drug release due to adsorption of SEDDS on CSD, implying dissolution at the pellet surface in parallel to that from the dispersed droplets. Compared to the commercial tablet, drug release from the self-emulsifying forms was faster at pH 1.2 where the drug solubility is poor, but slower at pH 6.8 where the solubility is higher. Permeability and cytotoxicity were also studied using Caco-2 cells. The results showed that drug transport from the apical to basolateral compartment of the test well was 1.27 times greater for SEPs than commercial tablets, but 0.86 times lower in the opposite direction. Statistical analysis confirmed the significance of these results. Toxicity was slightly reduced. Therefore, the increased permeability in conjunction with the protection of the drug being dissolved in the SEDDS droplets, may reduce the overall effect of presystemic metabolism and enhance bioavailability.

scholarly journals Bacterial Polyester Inclusions Engineered To Display Vaccine Candidate Antigens for Use as a Novel Class of Safe and Efficient Vaccine Delivery Agents

2009 ◽  
Vol 75 (24) ◽  
pp. 7739-7744 ◽  
Author(s):  
Natalie A. Parlane ◽  
D. Neil Wedlock ◽  
Bryce M. Buddle ◽  
Bernd H. A. Rehm
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Fusion Protein ◽  
Vaccine Delivery ◽  
Infectious Agent ◽  
Water Emulsion ◽  
Th2 Immune Response ◽  
Oil In Water Emulsion

ABSTRACT Bioengineered bacterial polyester inclusions have the potential to be used as a vaccine delivery system. The biopolyester beads were engineered to display a fusion protein of the polyester synthase PhaC and the two key antigens involved in immune response to the infectious agent that causes tuberculosis, Mycobacterium tuberculosis, notably antigen 85A (Ag85A) and the 6-kDa early secreted antigenic target (ESAT-6) from Mycobacterium tuberculosis. Polyester beads displaying the respective fusion protein at a high density were successfully produced (henceforth called Ag85A-ESAT-6 beads) by recombinant Escherichia coli. The ability of the Ag85A-ESAT-6 beads to enhance mouse immunity to the displayed antigens was investigated. The beads were not toxic to the animals, as determined by weight gain and absence of lesions at the inoculation site in immunized animals. In vivo injection of the Ag85A-ESAT-6 beads in mice induced significant humoral and cell-mediated immune responses to both Ag85A and ESAT-6. Vaccination with Ag85A-ESAT-6 beads was efficient at stimulating immunity on their own, and this ability was enhanced by administration of the beads in an oil-in-water emulsion. In addition, vaccination with the Ag85A-ESAT-6 beads induced significantly stronger humoral and cell-mediated immune responses than vaccination with an equivalent dose of the fusion protein Ag85A-ESAT-6 alone. The immune response induced by the beads was of a mixed Th1/Th2 nature, as assessed from the induction of the cytokine gamma interferon (Th1 immune response) and increased levels of immunoglobulin G1 (Th2 immune response). Hence, engineered biopolyester beads displaying foreign antigens represent a new class of versatile, safe, and biocompatible vaccines.

Effect of Freezing and Thawing Process on Betamethasone Acetate Release from Polyvinyl Alcohol Nanospheres

2009 ◽  
Vol 151 ◽  
pp. 159-165 ◽  
Author(s):  
Shahin Bonakdar ◽  
Seyed Ali Poursamar ◽  
Mohammad Rafienia ◽  
Mohammad A. Shokrgozar ◽  
Afshin Farhadi ◽  
...  
Keyword(s):  
Drug Release ◽  
Polyvinyl Alcohol ◽  
Freezing And Thawing ◽  
Drug Release Rate ◽  
Water Emulsion ◽  
Transmission Electron ◽  
Oil In Water ◽  
Thawing Process ◽  
Freezing Cycle ◽  
Oil In Water Emulsion

Betamethasone acetate (BA) is a glucocorticoid steroid with anti-inflammatory and immunosuppressive properties which can be used in treatment of asthma and itching. In this research, polyvinyl alcohol nanospheres loaded by betamethasone acetate were prepared by oil in water emulsion method after which they were exposed to 1, 2 and 4 cycles of freeze-thawing (F-T) process including 24 hours freezing cycle at -25 °C and 24 hours thawing at ambient temperature. Nanospheres fabrication was confirmed by transmission electron microscopy and betamethasone release was analyzed by UV spectrophotometer at 245 nm. The results revealed that by increasing the number of F-T cycles the rate of drug release decreased. The effect of BA concentration was also investigated on human chondrosarcoma (sw 1353). The MTT assay was utilized to assess the cell proliferation. The results showed that these biocompatible nanospheres can be used for sustained release of such drugs for more than four months and drug release rate can be effectively controlled by implementing F-T cycles.

In vivo drug release behavior in dogs from a new colon-targeted delivery system

1999 ◽  
Vol 57 (1) ◽  
pp. 45-53 ◽  
Author(s):  
Takashi Ishibashi ◽  
Harumi Hatano ◽  
Masao Kobayashi ◽  
Masakazu Mizobe ◽  
Hiroyuki Yoshino
Keyword(s):  
Drug Release ◽  
Delivery System ◽  
Targeted Delivery ◽  
Release Behavior ◽  
Drug Release Behavior ◽  
Targeted Delivery System

scholarly journals Preparation and Release Profiles in Vitro/Vivo of Galantamine Pamoate Loaded Poly (Lactideco-Glycolide) (PLGA) Microspheres

2021 ◽  
Vol 11 ◽  
Author(s):  
Liping Du ◽  
Shankui Liu ◽  
Guizhou Hao ◽  
Li Zhang ◽  
Miaomiao Zhou ◽  
...  
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Solvent Evaporation Method ◽  
Sustained Drug Release ◽  
Water Emulsion ◽  
Oil Water

Patient’s poor compliance and the high risk of toxic effects limit the clinical use of galantamine hydrobromide. To overcome these drawbacks, the sustained-release galantamine pamoate microspheres (GLT-PM-MS) were successfully developed using an oil/water emulsion solvent evaporation method in this study. Physicochemical properties of GLT-PM-MS were carefully characterized, and the in vitro and in vivo drug release behaviors were well studied. Results showed that the morphology of optimized microspheres were spherical with smooth surfaces and core-shell interior structure. Mean particle size, drug loading and entrapment efficiency were 75.23 ± 1.79 μm, 28.01 ± 0.81% and 87.12 ± 2.71%, respectively. The developed GLT-PM-MS were found to have a sustained release for about 24 days in vitro and the plasma drug concentration remained stable for 17 days in rats. These results indicated that GLT-PM-MS could achieve the sustained drug release purpose and be used in clinical trial.

scholarly journals Biodegradable magnetic microspheres for drug targeting, temperature controlled drug release, and hyperthermia

2019 ◽  
Vol 5 (1) ◽  
pp. 161-164 ◽  
Author(s):  
Diana Zahn ◽  
Andreas Weidner ◽  
Katayoun Saatchi ◽  
Urs O. Häfeli ◽  
Silvio Dutz
Keyword(s):  
Drug Release ◽  
Drug Targeting ◽  
Matrix Material ◽  
Controlled Drug Release ◽  
Magnetic Hyperthermia ◽  
Magnetic Microspheres ◽  
Magnetic Drug Targeting ◽  
Target Area ◽  
Water Emulsion ◽  
Oil In Water Emulsion

AbstractMagnetic microspheres (MMS) used for magnetic drug targeting consist of magnetic nanoparticles (MNP) and a pharmaceutical agent embedded in a polymeric matrix material. The application of MNP for drug targeting enables guiding the MMS to a target area, imaging the position of the MMS with magnetic particle imaging, and finally inducing drug release. As latter takes place by degradation of the MMS or diffusion through the matrix, an increase in temperature, e.g. through magnetic hyperthermia, leads to an accelerated drug release. Here, MMS consisting of poly(lactic-coglycolic) acid (PLGA) with different monomer ratios were prepared by an oil-in-water emulsion evaporation method. The model drug Camptothecin (CPT) and magnetic multicore nanoparticles (MCNP) with a high specific heating rate were embedded into the microspheres. We obtained MMS in the preferred size range of 1 to 2 μm with a concentration of MCNP of 16wt%, a drug load of about 0.5wt% and an excellent heating performance of 161 W/gMMS. Investigations of the drug release behaviour showed an accelerated drug release when increasing the temperature from 20 °C to 37 °C or 43 °C by using a water bath. In addition, an increase in drug release of about 50% through magnetic heating of the MMS up to 44 °C compared to 37 °C was observed. By this, a magnetic hyperthermia induced CPT release from PLGA MMS is demonstrated for the very first time.

Study on the Slow-release Mometasone Furoate Injection of PLGA for the Treatment of Knee Arthritis

2020 ◽  
Vol 17 ◽  
Author(s):  
Yutong Liang ◽  
Jiaojiao Zhang ◽  
Xinghua Zhao ◽  
Ming Wang ◽  
Shi Ding ◽  
...  
Keyword(s):  
Drug Release ◽  
Encapsulation Efficiency ◽  
Safety Evaluation ◽  
Mometasone Furoate ◽  
Pharmacokinetic Data ◽  
Potential Candidate ◽  
Water Emulsion

Purpose: The purpose of this study is to develop a new PLGA based formulation for microspheres, which aims to release mometasone furoate for one month, so as to improve compliance. Methods: The microspheres containing mometasone furoate were prepared by oil in water emulsion and solvent evaporation. The microspheres were characterized by surface morphology, shape, size and encapsulation efficiency. The release in vitro was studied in 37°C phosphate buffer, and in vivo, pharmacodynamics and preliminary safety evaluation were conducted in male Sprague Dawley rats. Results: The morphology results show that the microspheres have smooth surface, spherical shape and the average diameter of 2.320-5.679μm. The encapsulation efficiency of the microspheres loaded with mometasone furoate is in the range of 53.1% to 95.2%, and the encapsulation efficiency of the microspheres can be greatly affected by the proportion of oil phase to water phase and other formulation parameters. In vitro release kinetics revealed that drug release from microspheres was through non Fick's diffusion and PLGA polymer erosion. Pharmacokinetic data showed that the initial release of microspheres was small and then sustained. The results of pharmacodynamic study fully proved the effectiveness and long-term effect of mometasone furoate microspheres. The results of in vivo safety evaluation showed that the preparation system had good in vivo safety. Conclusion: This study shows that the microspheres prepared in this study have sufficient ability of stable drug release at least 35 days, with good efficacy and high safety. In addition, mometasone furoate can be used as a potential candidate drug for 35 day long-term injection.

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