scholarly journals Degradation behavior of theophylline/chitosan/?-cyclodextrin microspheres for pulmonary drug delivery

2016 ◽  
Vol 11 ◽  
pp. S116-S122 ◽  
Author(s):  
Li Wang ◽  
Tingting Yang ◽  
Weiping Ju ◽  
Ming Ren ◽  
Zhanqin Feng ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Phosphate Buffer ◽  
In Vitro Study ◽  
Pulmonary Drug Delivery ◽  
Degradation Behavior ◽  
Sprague Dawley ◽  
Phosphate Buffer Saline ◽  
Drug Delivery Carrier

To evaluate the degradation behavior of theophylline/chitosan/?-cyclo-dextrin microspheres, we performed both in vitro study by putting the microspheres in phosphate buffered saline or in phosphate buffer saline with enzyme and in vivo study by implanting the microspheres into the back of male Sprague-Dawley rats. The results showed that microspheres were degraded in enzymatic hydrolysis and phosphate buffer saline, which were degraded faster in 0.2 mg/mL lysozyme than in phosphate buffer saline. The morphology of microspheres in phosphate buffer saline and enzyme solution developed rough surfaces, and showed irregular shape and pores after 8 weeks. The microspheres were degraded in vivo within 8 weeks with irregular, sheet, porous morphology, and the diameters were smaller than 5 ?m. These results indicated that the theophylline/chitosan/?-cyclodextrin microspheres had a good degradation both in vitro and in vivo which can be used as a pulmonary drug delivery carrier. 

Inhibitory Effect of Resveratrol on the Pharmacokinetics of Ticagrelor in Vivo and Vitro

2021 ◽  
Author(s):  
Peng Wang ◽  
Xiao-Xia Hu ◽  
Ying-hui Li ◽  
Nan-Yong Gao ◽  
Guo-quan Chen ◽  
...  
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Control Group ◽  
Rat Liver Microsomes ◽  
Sprague Dawley ◽  
Group B

This study was to evaluate the effect of resveratrol on the pharmacokinetics of ticagrelor in rats and the metabolism of ticagrelor in human CYP3A4 and liver microsomes. Eighteen Sprague-Dawley rats were randomly divided into three groups: group A (control group), group B (50mg/kg resveratrol), and group C (150mg/kg resveratrol ). After 30 minutes administration of resveratrol, a single dose of ticagrelor (18mg/kg) was administered orally. The vitro experiment was performed to examine the influence of resveratrol on ticagrelor metabolism in CYP3A4*1, human, and rat liver microsomes. Serial biological samples were assayed by validated UHPLC-MS/MS methods. In vivo study, the AUC and Cmax of ticagrelor in group B and C appeared to be significantly higher than the control group, while Vz/F and CLz/F of ticagrelor in group B and C were significantly decreased. In vitro study, resveratrol exhibited an inhibitory effect on CYP3A4*1, human and rat liver microsomes. The IC50 values of resveratrol were 56.75μM，69.07μM and 14.22μM, respectively. Our results indicated that resveratrol had a inhibitory effect on the metabolism of ticagrelor in vitro and vivo. It should be paid more attention to the clinical combination of resveratrol with ticagrelor and ticagrelor plasma concentration should be monitored to avoid the occurrence of adverse reaction.

Biocompatibility and biodegradability of implantable drug delivery matrices based on novel poly(decane-co-tricarballylate) photocured elastomers

2012 ◽  
Vol 27 (1) ◽  
pp. 78-94 ◽  
Author(s):  
Mohamed A. Shaker ◽  
Noriko Daneshtalab ◽  
Jules J.E. Doré ◽  
Husam M. Younes
Keyword(s):  
Drug Delivery ◽  
Epithelial Cells ◽  
Degradation Products ◽  
Mitochondrial Activity ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Diphenyltetrazolium Bromide ◽  
Tissue Reactions

Visible light photo-cross-linked biodegradable amorphous elastomers based on poly(decane- co-tricarballylate) (PDET) with different cross-linking densities were synthesized, and their cytotoxicity, biocompatibility, and biodegradability were reported. Cytotoxicity of PDET extracts of the elastomers was assessed for mitochondrial succinate dehydrogenase activity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay) and inhibition of [3H] thymidine incorporation into DNA of epithelial cells. The in vivo biocompatibility and biodegradability were determined by subcutaneous implantation of PDET microcylinders in 25 male Sprague–Dawley rats over a period of 12 weeks. The in vivo changes in physical and mechanical parameters of the implants were compared with those observed in vitro. The treated epithelial cells revealed no signs of cytotoxicity, and the elastomer degradation products caused only a slight stimulation to both mitochondrial activity and DNA replication. The implants did not exhibit any macroscopic signs of inflammation or adverse tissue reactions at implant retrieval sites. The retrieved implanted microcylinders maintained their original geometry and extensibility in a manner similar to those observed in vitro. These new elastomers have excellent biocompatibility and are considered promising biomaterials for controlled drug delivery and tissue engineering applications.

scholarly journals Future outlook hydrodynamic drug delivery system of solid oral dosage form: Review

2021 ◽  
Vol 6 (3) ◽  
pp. 96-101
Author(s):  
Akhilesh Kumar Singh ◽  
Neeraj Sharma
Keyword(s):  
Drug Delivery ◽  
Therapeutic Efficacy ◽  
Dosage Form ◽  
In Vitro Study ◽  
Local Effect ◽  
Oral Dosage ◽  
In Vivo Evaluation ◽  
Absorption Window

Over the last few years, therapeutic efficacy of drugs that have poor bioavailability or narrow absorption window have challenged the pharmaceutical industry. In this framework, many Hydrodynamic Balance System (HBS) also known as Gastro retentive dosage forms (GRDFs) have been used to enhance the therapeutic efficacy of drugs. Such drug have a narrow absorption window, are unstable at higher pH, are soluble in acidic conditions, and are local effect in the gastric-part. The drug development with recent technology of various novel polymeric-based gastroretentive drug delivery technologies that may regulate the bioavailability and extend time of therapeutic efficacy of such drugs. Our focus on the significance of in vitro study and in vivo evaluation parameters of various HBS drugs along with their applications.  This study provides a promising platform for advantages and guide formulation of HBS dosage form were covered in detail.

scholarly journals Investigation of surface topography of different root-end filling materials: An in vitro study

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Mine Koruyucu ◽  
Hazal Özcan ◽  
Merve Bayram ◽  
Abdullah Burak Cankaya ◽  
Nurullah Keklikoglu ◽  
...  
Keyword(s):  
Surface Topography ◽  
Normal Saline ◽  
Phosphate Buffer ◽  
Saline Solution ◽  
In Vitro Study ◽  
Phosphate Buffer Saline ◽  
Filling Materials ◽  
Retrograde Filling ◽  
Group B

Aim: Although there are many materials that can be used for retrograde filling in surgical endodontics, none of them can be regarded as an ideal material yet. The purpose of this study was to compare the surface topography of three different root-end filling materials.Methods: 36 extracted single rooted human incisor teeth were cleaned and decoronated to standardized 10 mm root lengths. The root segments were prepared and 2 mm apical resection were performed. The samples were randomly separeted to three groups (Group A: Ca(OH)2, Group B: MTA Angelus, Group C: ProRoot MTA), each comprised of 12 roots. Materials were placed as 2 mm apical barriers and obturated with guttapercha and AH-Plus sealer. Each group dimidiated two subgroups (A1,A2,B1,B2,C1,C2). Groups A1,B1,C1 were stored in normal saline (NS), groups A2,B2,C2 were stored in neutral phosphate buffer saline (NPBS) solution and samples were incubated at 370C for 2 weeks. Stereomicroscope (32X) was used to photograph the root-end filling.Results: All specimens demonstrated white crystals formation and sediment over the root-end filling materials and on the superficial border of the root-end cavities’ wall as a white plague. A2,B2,C2 samples have more crystal sediment on root-end fillings than samples A1,B1,C1. Dissolution and corrosion were observed in groups A1, A2.Conclusions: The results of this study revealed that calcium hydroxide is more resorbable than MTA Angelus and ProRoot MTA. The crystals formation and precipitation were observed in neutral phosphate buffer saline solution was more than normal saline solution for all groups as a hydroxiapatite crystals.  

Chlorogenic acid differentially affects postprandial glucose and glucose-dependent insulinotropic polypeptide response in rats

2011 ◽  
Vol 36 (5) ◽  
pp. 650-659 ◽  
Author(s):  
Jasmine M. Tunnicliffe ◽  
Lindsay K. Eller ◽  
Raylene A. Reimer ◽  
Dustin S. Hittel ◽  
Jane Shearer
Keyword(s):  
Blood Glucose ◽  
Gastric Emptying ◽  
Coffee Consumption ◽  
In Vitro Study ◽  
Sprague Dawley ◽  
Glucose Response ◽  
Nonesterified Fatty Acids ◽  
Blood Glucose Response

Regular coffee consumption significantly lowers the risk of type 2 diabetes (T2D). Coffee contains thousands of compounds; however, the specific component(s) responsible for this reduced risk is unknown. Chlorogenic acids (CGA) found in brewed coffee inhibit intestinal glucose uptake in vitro. The objective of this study was to elucidate the mechanisms by which CGA acts to mediate blood glucose response in vivo. Conscious, unrestrained, male Sprague–Dawley rats were chronically catheterized and gavage-fed a standardized meal (59% carbohydrate, 25% fat, 12% protein), administered with or without CGA (120 mg·kg–1), in a randomized crossover design separated by a 3-day washout period. Acetaminophen was co-administered to assess the effects of CGA on gastric emptying. The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were measured. GLP-1 response in the presence of glucose and CGA was further examined, using the human colon cell line NCI-H716. Total area under the curve (AUC) for blood glucose was significantly attenuated in rats fed CGA (p < 0.05). Despite this, no differences in plasma insulin or nonesterified fatty acids were observed, and gastric emptying was not altered. Plasma GIP response was blunted in rats fed CGA, with a lower peak concentration and AUC up to 180 min postprandially (p < 0.05). There were no changes in GLP-1 secretion in either the in vivo or in vitro study. In conclusion, CGA treatment resulted in beneficial effects on blood glucose response, with alterations seen in GIP concentrations. Given the widespread consumption and availability of coffee, CGA may be a viable prevention tool for T2D.

scholarly journals Aesculus hippocastanum L. Extract Does Not Induce Fibroblast to Myofibroblast Conversion but Increases Extracellular Matrix Production In Vitro Leading to Increased Wound Tensile Strength in Rats

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1917
Author(s):  
Ivan Kováč ◽  
Nikola Melegová ◽  
Matúš Čoma ◽  
Peter Takáč ◽  
Katarína Kováčová ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Tensile Strength ◽  
Smooth Muscle Actin ◽  
In Vitro Study ◽  
Dermal Fibroblasts ◽  
Control Group ◽  
Horse Chestnut ◽  
Sprague Dawley

The ability of horse chestnut extract (HCE) to induce contraction force in fibroblasts, a process with remarkable significance in skin repair, motivated us to evaluate its wound healing potential in a series of experiments. In the in vitro study of the ability of human dermal fibroblasts to form myofibroblast-like cells was evaluated at the protein level (Western blot and immunofluorescence). The in vivo study was conducted on male Sprague-Dawley rats with inflicted wounds (one open circular and one sutured incision) on their backs. Rats were topically treated with two tested HCE concentrations (0.1% and 1%) or sterile water. The control group remained untreated. The incisions were processed for wound tensile strength (TS) measurement whereas the open wounds were subjected to histological examination. On the in vitro level the HCE extract induced fibronectin-rich extracellular matrix formation, but did not induced α-smooth muscle actin (SMA) expression in dermal fibroblasts. The animal study revealed that HCE increased wound TS and improved collagen organization. In conclusion, the direct comparison of both basic wound models demonstrated that the healing was significantly increased following HCE, thus this extract may be found useful to improve healing of acute wounds. Nevertheless, the use of an experimental rat model warrants a direct extrapolation to the human clinical situation.

scholarly journals In-vitro and in-vivo Characterization of a Multi-Stage Enzyme-Responsive Nanoparticle-in-Microgel Pulmonary Drug Delivery System

2019 ◽  
Author(s):  
Joscelyn C. Mejías ◽  
Krishnendu Roy
Keyword(s):  
Drug Delivery ◽  
Pulmonary Drug Delivery ◽  
Oil Emulsion ◽  
Multi Stage ◽  
Macrophage Phagocytosis ◽  
Efficient Delivery ◽  
Water In Oil Emulsion ◽  
In Vivo Characterization

AbstractAlthough the lung is an obvious target for site-specific delivery of many therapeutics for respiratory airway diseases such as asthma, COPD, and cystic fibrosis, novel strategies are needed to avoid key physiologic barriers for efficient delivery and controlled release of therapeutics to the lungs. Specifically, deposition into the deep lung requires particles with a 1-5 µm aerodynamic diameter; however, particles with a geometric diameter less than 6 µm are rapidly cleared by alveolar macrophages. Additionally, epithelial, endothelial, and fibroblast cells prefer smaller (< 300 nm) nanoparticles for efficient endocytosis. Here we address these contradictory design requirements by using a nanoparticle-inside-microgel system (Nano-in-Microgel). Using an improved maleimide-thiol based Michael Addition during (water-in-oil) Emulsion (MADE) method, we fabricated both trypsin-responsive and neutrophil elastase-responsive polymeric Nano-in-Microgel to show the versatility of the system in easily exchanging enzyme-responsive crosslinkers for disease-specific proteases. By varying the initial macromer concentration, from 20-50 % w/v, the size distribution means ranged from 4-8 µm, enzymatic degradation of the microgels is within 30 minutes, and in vitro macrophage phagocytosis is lower for the higher % w/v. We further demonstrated that in vivo lung delivery of the multi-stage carriers through the pulmonary route yields particle retention up to several hours and followed by clearance within in naïve mice. Our results provide a further understanding of how enzymatically-degradable multi-stage polymeric carriers can be used for pulmonary drug delivery.Graphical Abstract

scholarly journals Chrysanthemum indicum Attenuates Cisplatin-induced Nephrotoxicity both in vivo and in vitro

2015 ◽  
Vol 10 (3) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Tae-Won Kim ◽  
Young-Jung Kim ◽  
So-Ra Park ◽  
Chang-Seob Seo ◽  
Hyekyung Ha ◽  
...  
Keyword(s):  
Protective Effect ◽  
Inflammatory Diseases ◽  
In Vitro Study ◽  
Ethanol Extract ◽  
Sprague Dawley ◽  
Pk15 Cell ◽  
P53 Expression ◽  
Chrysanthemum Indicum

Chrysanthemum indicum Linné has been used in traditional medicine to treat various inflammatory diseases in East Asia. The aim of the present study was to investigate the protective effect of C. indicum ethanol extract (CILE) against cisplatin-induced nephrotoxicity. An HPLC-photodiode array method was used for fingerprint analysis of the CILE and ten major constituents were quantitatively analyzed. The protective effect of CILE on cisplatin-induced nephrotoxicity was assessed using both in vitro (porcine kidney cell; PK15 cell) and in vivo (Sprague Dawley rat) experiments. In the in vitro study, CILE enhanced PK15 cell viability after cisplatin treatment with recovered antioxidant status. Moreover, the increased p53 expression after cisplatin treatment was decreased in the CILE pretreated cells. In the in vivo study, SD rats were treated for 28 consecutive days with CILE (0, 100, 300 and 500 mg/kg). On day 23, a single dose of cisplatin (5 mg/kg) was injected to induce nephrotoxicity. The CILE pretreated group showed recovered serum renal function index with ameliorated oxidative stress. Histopathological alterations and apoptosis in the kidney were also decreased in CILE pretreated rats. Taken together, CILE could attenuate cisplatin-induced nephrotoxicity and might be a beneficial agent for acute renal failure management.

Nano-Liposomal Dry Powder Inhaler of Amiloride Hydrochloride

2006 ◽  
Vol 6 (9) ◽  
pp. 3001-3009 ◽  
Author(s):  
Mahavir Bhupal Chougule ◽  
Bijay Kumar Padhi ◽  
Ambikanandan Misra
Keyword(s):  
Cystic Fibrosis ◽  
Drug Release ◽  
Phosphate Buffer ◽  
Dry Powder Inhaler ◽  
Dry Powder ◽  
Phosphate Buffer Saline ◽  
Amiloride Hydrochloride ◽  
Spray Dried

The purpose of this study was to encapsulate Amiloride Hydrochloride into nano-liposomes, incorporate it into dry powder inhaler, and to provide prolonged effective concentration in airways to enhance mucociliary clearance and prevent secondary infection in cystic fibrosis. Liposomes were prepared by thin film hydration technique and then dispersion was passed through high pressure homogenizer to achieve size of nanometer range. Nano-liposomes were separated by centrifugation and were characterized. They were dispersed in phosphate buffer saline pH 7.4 containing carriers (lactose/sucrose/mannitol), and glycine as anti-adherent. The resultant dispersion was spray dried. The spray dried powders were characterized and in vitro drug release studies were performed using phosphate buffer saline pH 7.4. in vitro and in vivo drug pulmonary deposition was carried out using Andersen Cascade Impactor and by estimating drug in bronchial alveolar lavage and lung homogenate after intratracheal instillation in rats respectively. Nano-liposomes were found to have mean volume diameter of 198 ± 15 nm, and 57% ± 1.9% of drug entrapment. Mannitol based formulation was found to have low density, good flowability, particle size of 6.7 ± 0.6 μm determined by Malvern MasterSizer, maximum fine particle fraction of 67.6 ± 0.6%, mean mass aerodynamic diameter 2.3 ± 0.1 μm, and geometric standard deviation 2.4 ± 0.1. Developed formulations were found to have prolonged drug release following Higuchi's Controlled Release model and in vivo studies showed maximal retention time of drug of 12 hrs within the lungs and slow clearance from the lungs. This study provides a practical approach for direct lung delivery of Amiloride Hydrochloride encapsulated in liposomes for controlled and prolonged retention at the site of action from dry powder inhaler. It can provide a promising alternative to the presently available nebulizers in terms of prolonged pharmacological effect, reducing systemic side effects such as potassium retention due to rapid clearance of the drug from lungs in patients suffering from cystic fibrosis.

scholarly journals Environmentally Relevant Iron Oxide Nanoparticles Produce Limited Acute Pulmonary Effects in Rats at Realistic Exposure Levels

2021 ◽  
Vol 22 (2) ◽  
pp. 556
Author(s):  
Chang Guo ◽  
Ralf J. M. Weber ◽  
Alison Buckley ◽  
Julie Mazzolini ◽  
Sarah Robertson ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Particle Deposition ◽  
Clinical Signs ◽  
In Vitro Study ◽  
Sprague Dawley ◽  
Iron Oxide Particles ◽  
High Iron Content ◽  
Cell Counts

Iron is typically the dominant metal in the ultrafine fraction of airborne particulate matter. Various studies have investigated the toxicity of inhaled nano-sized iron oxide particles (FeOxNPs) but their results have been contradictory, with some indicating no or minor effects and others finding effects including oxidative stress and inflammation. Most studies, however, did not use materials reflecting the characteristics of FeOxNPs present in the environment. We, therefore, analysed the potential toxicity of FeOxNPs of different forms (Fe3O4, α-Fe2O3 and γ-Fe2O3) reflecting the characteristics of high iron content nano-sized particles sampled from the environment, both individually and in a mixture (FeOx-mix). A preliminary in vitro study indicated Fe3O4 and FeOx-mix were more cytotoxic than either form of Fe2O3 in human bronchial epithelial cells (BEAS-2B). Follow-up in vitro (0.003, 0.03, 0.3 µg/mL, 24 h) and in vivo (Sprague–Dawley rats, nose-only exposure, 50 µg/m3 and 500 µg/m3, 3 h/d × 3 d) studies therefore focused on these materials. Experiments in vitro explored responses at the molecular level via multi-omics analyses at concentrations below those at which significant cytotoxicity was evident to avoid detection of responses secondary to toxicity. Inhalation experiments used aerosol concentrations chosen to produce similar levels of particle deposition on the airway surface as were delivered in vitro. These were markedly higher than environmental concentrations. No clinical signs of toxicity were seen nor effects on BALF cell counts or LDH levels. There were also no significant changes in transcriptomic or metabolomic responses in lung or BEAS-2B cells to suggest adverse effects.

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