scholarly journals Design and Optimization of a Novel-Herbosomal Loaded PEG-Poloxamer Topical Formulation For the Treatment of Cold Injuries: A Quality By Design Approach

2021 ◽  
Author(s):  
Renu Bala Yadav ◽  
Dharam Pal Pathak ◽  
Rajeev Varshney ◽  
Rajesh Arora
Keyword(s):  
Lipid Vesicles ◽  
Cold Injury ◽  
Treatment Modalities ◽  
Limb Amputation ◽  
P Value ◽  
Release Kinetic ◽  
Crystal Formation ◽  
Sprague Dawley ◽  
Topical Formulation

Abstract Cold injury/injuries can range from minor chilblain to extreme form of frostbite. Cold injuries are pathologically a combination of ice crystal formation in tissue with inflammation, thrombosis and ischemia to extremities, necessitating limb amputation in extreme cases due to tissue necrosis. Less severe forms of cold injuries can be managed by gentle rewarming of limb and avoiding exposure to cold leading to favorable outcomes, however severe forms of frostbite are a cause of major concern to patients as well as the treating physician. Due to lack of effective pre-treatment modalities and paucity of research in prophylaxis and therapeutics of cold injuries, we have developed a novel-herbosomal loaded PEG-Poloxamer topical formulation (n-HPTF) by Quality by Designed approach, incorporating natural ingredients which are having potential therapeutic effect for the treatment of cold injury in a form of a novel-lipid vesicles (herbosomes) loaded in polymers (PEG-3350 and Poloxamer-188) resulting excellent occlusive barrier and thus promote rapid healing. Optimized novel-herbosomes showed entrapment efficiency > 90% and < 300 nm mean particle size and in-vitro drug permeation of about 2 µg/cm2 followed by Higuchi’s release kinetic. Skin irritancy study on female Sprague Dawley rats showed no edema or erythema. In-vivo bio-efficacy study was performed and found significantly good at p-value < 0.05 when compared to the standard treatment groups.

Abstract 174: Periadventitial or Intraluminal Delivery of Simvastatin Attenuates Intimal Hyperplasia After Arterial Injury

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Alex Helkin ◽  
David Bruch ◽  
David R Wilson ◽  
Rebecca Bader ◽  
Kristopher G Maier ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Intimal Hyperplasia ◽  
Oral Delivery ◽  
Arterial Injury ◽  
Treatment Modalities ◽  
Boyden Chamber ◽  
Sprague Dawley ◽  
Balloon Injury ◽  
Sd Rats

Introduction: Oral statin administration reduces intimal hyperplasia (IH) after arterial injury by only ~25%. Alternative drug delivery systems have gained attention as carriers for hydrophobic drugs. We studied the effects of simvastatin (free vs hyaluronic acid tagged polysialic acid-polycaprolactone micelles) in vitro on vascular smooth muscle cell (VSMC) migration and in vivo after arterial injury. We hypothesized both free and micelles containing statins would inhibit VSMC chemotaxis and local statin treatment would reduce IH in Sprague-Dawley (SD) rats following carotid balloon injury greater than oral delivery. Methods: VSMCs pretreated with free simvastatin (1 μM, 20 min or 20 hrs) or simvastatin-loaded micelles underwent chemotaxis to thrombospondin-1 (20 μg/mL) or serum-free media using a modified Boyden chamber. Next, SD rats (13-15 wks) who underwent balloon injury of the common carotid artery (5 atm/5 min) received statin therapy – either intraluminal simvastatin loaded micelles (50 μM, pressurized for 5 min) prior to injury or periadventitial pluronic gel (50 μM simvastatin) following injury. Arteries were harvested 14 days postoperatively. Morphometric analysis was performed using the intimal/media area ratio defined as intima/(intima + media). Findings were compared to our historic animals which received oral simvastatin (10 mg/kg/day) or controls without statin therapy. Statistical analysis was by ANOVA and p <0.05 was significant. Results: Simvastatin loaded micelles and free simvastatin inhibited VSMC chemotaxis (54%-60%, p <0.05). IH was induced in all injured vessels. Simvastatin in pluronic gel or micelles reduced IH compared to untreated controls (0.208 ± 0.04 or 0.160 ± 0.03 vs 0.350 ± 0.03, respectively, p <0.05). However, neither gel nor simvastatin-loaded micelles were superior to oral statins (0.261 ± 0.03, p >0.05). Conclusions: Intraluminally and periadventially delivered statins were effective in reducing IH. The efficacy of single dose, locally delivered statins alone may lead to novel treatment modalities for the prevention of IH. The different routes of administration allow for treatment at the time of both open and endovascular procedures, without the need for systemic therapy.

scholarly journals FORMULATION AND EVALUATION OF ANTIFUNGAL NANOGEL FOR TOPICAL DRUG DELIVERY SYSTEM

2021 ◽  
pp. 127-134
Author(s):  
ANASUYA PATIL ◽  
PRANOTI KONTAMWAR
Keyword(s):  
Research Work ◽  
In Vitro Release ◽  
Gelling Agent ◽  
Release Kinetic ◽  
Topical Formulation ◽  
Ciclopirox Olamine ◽  
Carbopol 940 ◽  
Vitro Release

Objective: Ciclopirox olamine has been used as antifungal agent. It is used as topical formulation because oral route causes irritation and ulceration of GIT. In this research work, antifungal nanogel formulated to reduce size of particle, improve in-vitro release and in-vivo release. Methods: Ciclopirox olamine nanogel was prepared by homogenization technique and incorporation of gelling agent to produce nanogel. Ciclopirox olamine nanogel formulated using Carbopol 940. Results: Antigungal Nanogels (F1-F6) were subjected to FT-IR analysis and showed no interaction between the drug and excipients. The best formulation (F6) elicited the high in-vitro release of 83.42 % at 8 hours; zeta-potential and particle size, obtained values were 230 nm and -27 mV correspondingly. In-vitro release kinetic models were shown that formulation-F6 follows First-order kinetics and high regression coefficient value r2 0.9866. SEM image of the best formulation-F6 depicts that no breakage of nanogel. The differential scanning calorimetry thermogram of ciclopirox olamine was found to be 140.09.7°C. The DSC thermogram of physical mixture of carbopol 940 and Euragit-S 100 was found to be 1290C and 218 0C. DSC study of nanogel (F6) showed no interaction between drug and excipients. The best formulation-F6 was subjected to in-vivo study on mice which showed better effect in treating dermatitis. Conclusion: It would be concluded that the best formulation-F6 which elicited better in-vitro drug release and enhanced dermatitis scoring. Keywords: Ciclopirox-olamine, Eudragit-S100, Glycerol, Dermatitis, Carbopol-940, Cellophane membrane.

Preparation of cultured astrocytes for x-ray microanalysis

1989 ◽  
Vol 47 ◽  
pp. 988-989
Author(s):  
N.K.R. Smith ◽  
K.E. Hunter ◽  
P. Mobley ◽  
L.P. Felpel
Keyword(s):  
Cultured Cells ◽  
Elemental Content ◽  
Elemental Distribution ◽  
Sprague Dawley ◽  
X Ray ◽  
Cultured Astrocytes ◽  
Freeze Dried ◽  
Ultimate Objective

Electron probe energy dispersive x-ray microanalysis (XRMA) offers a powerful tool for the determination of intracellular elemental content of biological tissue. However, preparation of the tissue specimen , particularly excitable central nervous system (CNS) tissue , for XRMA is rather difficult, as dissection of a sample from the intact organism frequently results in artefacts in elemental distribution. To circumvent the problems inherent in the in vivo preparation, we turned to an in vitro preparation of astrocytes grown in tissue culture. However, preparations of in vitro samples offer a new and unique set of problems. Generally, cultured cells, growing in monolayer, must be harvested by either mechanical or enzymatic procedures, resulting in variable degrees of damage to the cells and compromised intracel1ular elemental distribution. The ultimate objective is to process and analyze unperturbed cells. With the objective of sparing others from some of the same efforts, we are reporting the considerable difficulties we have encountered in attempting to prepare astrocytes for XRMA.Tissue cultures of astrocytes from newborn C57 mice or Sprague Dawley rats were prepared and cultured by standard techniques, usually in T25 flasks, except as noted differently on Cytodex beads or on gelatin. After different preparative procedures, all samples were frozen on brass pins in liquid propane, stored in liquid nitrogen, cryosectioned (0.1 μm), freeze dried, and microanalyzed as previously reported.

Design and Synthesis of a Novel Gabapentin-Phosphotidylcholine Conjugate for Targeting to Phospholipase A2 Enzyme through Nanostructured Lipid Carrier

2020 ◽  
Vol 16 ◽  
Author(s):  
Anjali P.B ◽  
Jawahar N. ◽  
Jubie S. ◽  
Neetu Yadav ◽  
Selvaraj A. ◽  
...  
Keyword(s):  
Drug Release ◽  
Phospholipase A2 ◽  
Release Kinetics ◽  
Entrapment Efficiency ◽  
Structural Analog ◽  
Fickian Diffusion ◽  
Release Kinetic ◽  
Nanostructured Lipid Carrier ◽  
Discovery Studio

Background: : Epilepsy is a genuine neurological turmoil that effects around 50 million individuals around the world. Practically 30% of epileptic patients experience the ill effects of pharmaco-obstruction, which is related with social seclusion, subordinate conduct, low marriage rates, joblessness, mental issues and diminished personal satisfaction. At present accessible antiepileptic drugs have a restricted viability, and their negative properties limit their utilization and cause challenges in patient administration. Gabapentin 1-(aminomethyl)cyclohexane acetic acid, Gbp , (trade name Neurontin), a structural analog of γ-aminobutyric acid (GABA), BCS class 3 drug with having permeability issues. Objective: This work was an attempt to formulate and characterize a new approach to treat epilepsy by targeting to Phospholipase A2 Enzyme through Nanostructured Lipid Carrier. Methods: Docking studied carried out using Accelrys Discovery studio 4.1 Client and gabapentin and phosphotidylcholine were conjugated through chemical conjugation. Nanostructured lipid carrier (NLC) was prepared using hot homogenization technique. Results: The libdock score of Gabapentin- Phosphotidylcholine conjugate (192.535) were found to be more than Gabapentin (77.1084) and Phosphotidylcholine (150.212). For the optimized formulation the particle size (50.08), zeta potential (-1.48), PDI (0.472) and entrapment efficiency (77.8) was observed. The NLC was studies for in-vitro drug release studies and release kinetics. Finally found that the drug release from the NLC followed Higuchi release kinetic and the mode of drug release from the NLC was found to be Non- Fickian diffusion. Conclusion: The formulated Nanostructured lipid carrier of Gabapentin-Phosphotidylcholine conjugate may be able to use to prevent seizure.

scholarly journals Inhibitory Effects of a Reengineered Anthrax Toxin on Canine Oral Mucosal Melanomas

Toxins ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 157 ◽  
Author(s):  
Adriana Tomoko Nishiya ◽  
Marcia Kazumi Nagamine ◽  
Ivone Izabel Mackowiak da Fonseca ◽  
Andrea Caringi Miraldo ◽  
Nayra Villar Scattone ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Evaluation Criteria ◽  
Anthrax Toxin ◽  
Treatment Modalities ◽  
Inhibitory Effects ◽  
Upa Receptor ◽  
New Treatment ◽  
Oral Malignancy

Canine oral mucosal melanomas (OMM) are the most common oral malignancy in dogs and few treatments are available. Thus, new treatment modalities are needed for this disease. Bacillus anthracis (anthrax) toxin has been reengineered to target tumor cells that express urokinase plasminogen activator (uPA) and metalloproteinases (MMP-2), and has shown antineoplastic effects both, in vitro and in vivo. This study aimed to evaluate the effects of a reengineered anthrax toxin on canine OMM. Five dogs bearing OMM without lung metastasis were included in the clinical study. Tumor tissue was analyzed by immunohistochemistry for expression of uPA, uPA receptor, MMP-2, MT1-MMP and TIMP-2. Animals received either three or six intratumoral injections of the reengineered anthrax toxin prior to surgical tumor excision. OMM samples from the five dogs were positive for all antibodies. After intratumoral treatment, all dogs showed stable disease according to the canine Response Evaluation Criteria in Solid Tumors (cRECIST), and tumors had decreased bleeding. Histopathology has shown necrosis of tumor cells and blood vessel walls after treatment. No significant systemic side effects were noted. In conclusion, the reengineered anthrax toxin exerted inhibitory effects when administered intratumorally, and systemic administration of this toxin is a promising therapy for canine OMM.

An In Vitro Cytotoxicity Assay Using Rat Hepatocytes and MTT and Coomassie Blue Dye as Indicators

1991 ◽  
Vol 19 (3) ◽  
pp. 352-360
Author(s):  
Kazuhiko Otoguro ◽  
Kanki Komiyama ◽  
Satoshi Ωmura ◽  
Charles A. Tyson
Keyword(s):  
Mtt Assay ◽  
Membrane Integrity ◽  
Cell Number ◽  
Cellular Protein ◽  
Blue Dye ◽  
Tetrazolium Salt ◽  
Sprague Dawley ◽  
Lactate Dehydrogenase Activity ◽  
Coomassie Blue

Isolated hepatocytes from male Sprague-Dawley rats suspended in culture medium supplemented with either 0.2 or 2% bovine serum albumin (BSA) were allowed to attach to collagen coated 96-well dishes. Ten test chemicals from the MEIC list and salicylic acid were added individually to the dishes, and at the end of 24 and 48 hours, cytotoxicity was determined by measuring MTT (tetrazolium salt) reduction (mitochondrial integrity) and total cellular protein using Coomassie blue dye (reflecting cell number). Total cellular lactate dehydrogenase activity was also determined in some experiments, as an indicator of plasma membrane integrity. The relative toxicities of the test chemicals were quantified by the estimation of EC10, EC20 and EC50 values for each parameter. Except for one chemical, digoxin, in the MTT assay, cytotoxic potency increased with incubation time. The hepatocytes tended to be more sensitive to the chemicals in medium containing 0.2% BSA than in medium containing 2% BSA. Simple linear regression analyses of the log transformed data from the MTT assay versus log oral LD50 in rats for the test chemicals gave the best results using EC10 at 24 hours (r2 = 0.86). With protein as the cytotoxic indicator, the best results were obtained with EC values in the medium containing 2% BSA, again at 24 hours (r2 = 0.83). These results suggest that the MTT and Coomassie blue dye assays could be useful indicators for testing the cytotoxic potential of chemicals in rat hepatocyte cultures.

scholarly journals Development and Evaluation of Fluoxetine Fast Dissolving Films: An Alternative for Noncompliance in Pediatric Patients

Processes ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 778
Author(s):  
Emőke-Margit Rédai ◽  
Paula Antonoaea ◽  
Nicoleta Todoran ◽  
Robert Alexandru Vlad ◽  
Magdalena Bîrsan ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Hydroxypropyl Methylcellulose ◽  
Pharmaceutical Formulations ◽  
Release Kinetic ◽  
Disintegration Time ◽  
Casting Technique ◽  
First Order ◽  
Orodispersible Films ◽  
Folding Endurance

The most used pharmaceutical formulations for children are syrups, suppositories, soft chewable capsules, and mini-tablets. Administrating them might create an administration discomfort. This study aimed to develop and evaluate orodispersible films (ODFs) for pediatric patients in which the fluoxetine (FX) is formulated in the polymeric matrix. Six FX fast dissolving films (10 mg FX/ODF), FX1, FX2, FX3, FX4, FX5, and FX6, were prepared by solvent casting technique. In the composition of the ODFs, the concentration of the hydroxypropyl methylcellulose and the concentration of the propylene glycol were varied. Each formulation of fluoxetine ODF was evaluated by determining the tensile strength, folding endurance, disintegration, behavior in the controlled humidity and temperature conditions, and adhesiveness. All the obtained results were compared with the results obtained for six ODFs prepared without FX. The disintegration time of the FX ODFs was of maximum 88 s for FX2. Via the in vitro releasing study of the FX from the ODFs it was noticed that FX1 and FX2 allow a better release of the drug 99.98 ± 3.81% and 97.67 ± 3.85% being released within 15 min. From the obtained results it was also confirmed that FX ODFs were found to follow first-order release kinetic.

scholarly journals Stamina-Enhancing Effects of Human Adipose-Derived Stem Cells

2021 ◽  
Vol 30 ◽  
pp. 096368972110354
Author(s):  
Eun-Jung Yoon ◽  
Hye Rim Seong ◽  
Jangbeen Kyung ◽  
Dajeong Kim ◽  
Sangryong Park ◽  
...  
Keyword(s):  
Physical Activity ◽  
Stem Cells ◽  
Locomotor Activity ◽  
Tissue Injury ◽  
Male Rats ◽  
Adipose Derived Stem Cells ◽  
Sprague Dawley ◽  
Serum Triglycerides

Stamina-enhancing effects of human adipose derived stem cells (hADSCs) were investigated in young Sprague-Dawley rats. Ten-day-old male rats were transplanted intravenously (IV) or intracerebroventricularly (ICV) with hADSCs (1 × 106 cells/rat), and physical activity was measured by locomotor activity and rota-rod performance at post-natal day (PND) 14, 20, 30, and 40, as well as a forced swimming test at PND 41. hADSCs injection increased the moving time in locomotor activity, the latency in rota-rod performance, and the maximum swimming time. For the improvement of physical activity, ICV transplantation was superior to IV injection. In biochemical analyses, ICV transplantation of hADSCs markedly reduced serum creatine phosphokinase, lactate dehydrogenase, alanine transaminase, and muscular lipid peroxidation, the markers for muscular and hepatic injuries, despite the reduction in muscular glycogen and serum triglycerides as energy sources. Notably, hADSCs secreted brain-derived neurotrophic factor (BDNF) and nerve growth factor in vitro, and increased the level of BDNF in the brain and muscles in vivo. The results indicate that hADSCs enhance physical activity including stamina not only by attenuating tissue injury, but also by strengthening the muscles via production of BDNF.

scholarly journals Expression Profile of New Marker Genes Involved in Differentiation of Canine Adipose-Derived Stem Cells into Osteoblasts

2021 ◽  
Vol 22 (13) ◽  
pp. 6663
Author(s):  
Maurycy Jankowski ◽  
Mariusz Kaczmarek ◽  
Grzegorz Wąsiatycz ◽  
Claudia Dompe ◽  
Paul Mozdziak ◽  
...  
Keyword(s):  
Stem Cells ◽  
In Vitro Culture ◽  
Osteogenic Differentiation ◽  
Molecular Mechanisms ◽  
Marker Genes ◽  
P Value ◽  
Illumina Platform

Next-generation sequencing (RNAseq) analysis of gene expression changes during the long-term in vitro culture and osteogenic differentiation of ASCs remains to be important, as the analysis provides important clues toward employing stem cells as a therapeutic intervention. In this study, the cells were isolated from adipose tissue obtained during routine surgical procedures and subjected to 14-day in vitro culture and differentiation. The mRNA transcript levels were evaluated using the Illumina platform, resulting in the detection of 19,856 gene transcripts. The most differentially expressed genes (fold change >|2|, adjusted p value < 0.05), between day 1, day 14 and differentiated cell cultures were extracted and subjected to bioinformatical analysis based on the R programming language. The results of this study provide molecular insight into the processes that occur during long-term in vitro culture and osteogenic differentiation of ASCs, allowing the re-evaluation of the roles of some genes in MSC progression towards a range of lineages. The results improve the knowledge of the molecular mechanisms associated with long-term in vitro culture and differentiation of ASCs, as well as providing a point of reference for potential in vivo and clinical studies regarding these cells’ application in regenerative medicine.

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