scholarly journals Drug delivery of 6-bromoindirubin-3’-glycerol-oxime ether employing poly(d,l-lactide-co-glycolide)-based nanoencapsulation techniques with sustainable solvents

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Anna Czapka ◽  
Christian Grune ◽  
Patrick Schädel ◽  
Vivien Bachmann ◽  
Karl Scheuer ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Mammalian Cells ◽  
Glycogen Synthase ◽  
Lipid Mediators ◽  
Aqueous Environment ◽  
Human Monocytes ◽  
Oxime Ether ◽  
Cytotoxic Effects ◽  
The Poor ◽  
Sustainable Solvents

Abstract Background Insufficient solubility and stability of bioactive small molecules as well as poor biocompatibility may cause low bioavailability and are common obstacles in drug development. One example of such problematic molecules is 6-bromoindirubin-3'-glycerol-oxime ether (6BIGOE), a hydrophobic indirubin derivative. 6BIGOE potently modulates the release of inflammatory cytokines and lipid mediators from isolated human monocytes through inhibition of glycogen synthase kinase-3 in a favorable fashion. However, 6BIGOE suffers from poor solubility and short half-lives in biological aqueous environment and exerts cytotoxic effects in various mammalian cells. In order to overcome the poor water solubility, instability and cytotoxicity of 6BIGOE, we applied encapsulation into poly(d,l-lactide-co-glycolide) (PLGA)-based nanoparticles by employing formulation methods using the sustainable solvents Cyrene™ or 400 g/mol poly(ethylene glycol) as suitable technology for efficient drug delivery of 6BIGOE. Results For all preparation techniques the physicochemical characterization of 6BIGOE-loaded nanoparticles revealed comparable crystallinity, sizes of about 230 nm with low polydispersity, negative zeta potentials around − 15 to − 25 mV, and biphasic release profiles over up to 24 h. Nanoparticles with improved cellular uptake and the ability to mask cytotoxic effects of 6BIGOE were obtained as shown in human monocytes over 48 h as well as in a shell-less hen’s egg model. Intriguingly, encapsulation into these nanoparticles fully retains the anti-inflammatory properties of 6BIGOE, that is, favorable modulation of the release of inflammation-relevant cytokines and lipid mediators from human monocytes. Conclusions Our formulation method of PLGA-based nanoparticles by applying sustainable, non-toxic solvents is a feasible nanotechnology that circumvents the poor bioavailability and biocompatibility of the cargo 6BIGOE. This technology yields favorable drug delivery systems for efficient interference with inflammatory processes, with improved pharmacotherapeutic potential. Graphical Abstract

Hydrogels: A Versatile Drug Delivery Carrier Systems

1970 ◽  
Vol 5 (3) ◽  
pp. 1745-1756
Author(s):  
L H Baldaniya ◽  
Sarkhejiya N A
Keyword(s):  
Drug Delivery ◽  
Protein Delivery ◽  
Structural Integrity ◽  
Healing Process ◽  
Polymer Chains ◽  
Wound Healing Process ◽  
Aqueous Environment ◽  
Preparation Methods ◽  
Control Drug

Hydrogels are the material of choice for many applications in regenerative medicine due to their unique properties including biocompatibility, flexible methods of synthesis, range of constituents, and desirable physical characteristics. Hydrogel (also called Aquagel) is a network of polymer chains that are hydrophilic, sometimes found as a colloidal gel in which water is the dispersion medium. Hydrogels are highly absorbent (contain ~99.9% water), natural or synthetic polymers. Hydrogel also possess a degree of flexibility very similar to natural tissue, due to its significant water content. It can serve as scaffolds that provide structural integrity to tissue constructs, control drug and protein delivery to tissues and cultures. Also serve as adhesives or barriers between tissue and material surfaces. The positive effect of hydrogels on wounds and enhanced wound healing process has been proven. Hydrogels provide a warm, moist environment for wound that makes it heal faster in addition to its useful mucoadhesive properties. Moreover, hydrogels can be used as carriers for liposomes containing variety of drugs, such as antimicrobial drugs. Hydrogels are water swollen polymer matrices, with a tendency to imbibe water when placed in aqueous environment. This ability to swell, under biological conditions, makes it an ideal material for use in drug delivery and immobilization of proteins, peptides, and other biological compounds. Hydrogels have been extensively investigated for use as constructs to engineer tissues in vitro. This review describes the properties, classification, preparation methods, applications, various monomer used in formulation and development of hydrogel products.

scholarly journals Cytotoxic Effects of Hexavalent and Trivalent Chromium on Mammalian Cells In Vitro

1978 ◽  
Vol 37 (3) ◽  
pp. 386-396 ◽  
Author(s):  
A G Levis ◽  
V Bianchi ◽  
G Tamino ◽  
B Pegoraro
Keyword(s):  
Mammalian Cells ◽  
Trivalent Chromium ◽  
Cytotoxic Effects

Fabrication of Hybrid Cell-Microbead Constructs Using Laser Direct-Write of Alginate Microbeads and Adherent Breast Cancer Cells

2013 ◽  
Author(s):  
Andrew D. Dias ◽  
David M. Kingsley ◽  
Douglas B. Chrisey ◽  
David T. Corr
Keyword(s):  
Drug Delivery ◽  
Mammalian Cells ◽  
Hybrid Cell ◽  
High Surface ◽  
High Surface Area ◽  
Volume Ratio ◽  
Direct Write ◽  
Cellular Interactions ◽  
Paracrine Signaling ◽  
Laser Direct Write

Microbeads are becoming popular tools in tissue engineering as 3D microstructure hydrogels. The gel nature of microbeads enables them to sequester soluble factors and mammalian cells, and their high surface area-to-volume ratio allows diffusion between the bead and the environment [1,2]. Microbeads are thus good systems for drug delivery and can serve as 3D microenvironments for cells. To fully maximize their potential as delivery systems and microenvironments, it is highly desirable to create spatially-precise hybrid cultures of microbeads and mammalian cells. Precise placement of microbeads in proximity to patterned cells will allow the study of spatial cellular interactions, paracrine signaling, and drug delivery.

scholarly journals Molecular Mechanisms of Zinc Oxide Nanoparticle-Induced Genotoxicity

Materials ◽  
2017 ◽  
Vol 10 (12) ◽  
pp. 1427 ◽  
Author(s):  
Agmal Scherzad ◽  
Till Meyer ◽  
Norbert Kleinsasser ◽  
Stephan Hackenberg
Keyword(s):  
Dna Damage ◽  
Zinc Oxide ◽  
Mammalian Cells ◽  
Oxidative Dna Damage ◽  
Molecular Mechanisms ◽  
Consumer Products ◽  
Zno Nps ◽  
Cytotoxic Effects

Background: Zinc oxide nanoparticles (ZnO NPs) are among the most frequently applied nanomaterials in consumer products. Evidence exists regarding the cytotoxic effects of ZnO NPs in mammalian cells; however, knowledge about the potential genotoxicity of ZnO NPs is rare, and results presented in the current literature are inconsistent. Objectives: The aim of this review is to summarize the existing data regarding the DNA damage that ZnO NPs induce, and focus on the possible molecular mechanisms underlying genotoxic events. Methods: Electronic literature databases were systematically searched for studies that report on the genotoxicity of ZnO NPs. Results: Several methods and different endpoints demonstrate the genotoxic potential of ZnO NPs. Most publications describe in vitro assessments of the oxidative DNA damage triggered by dissoluted Zn2+ ions. Most genotoxicological investigations of ZnO NPs address acute exposure situations. Conclusion: Existing evidence indicates that ZnO NPs possibly have the potential to damage DNA. However, there is a lack of long-term exposure experiments that clarify the intracellular bioaccumulation of ZnO NPs and the possible mechanisms of DNA repair and cell survival.

Innovative Strategies for Lipid-Based Drug Delivery

2018 ◽  
pp. 60-84 ◽  
Author(s):  
Navneet Sharma ◽  
Sabna Kotta ◽  
Mohd Aleem ◽  
Shubham Singh ◽  
Rakesh Kumar Sharma
Keyword(s):  
Drug Delivery ◽  
Drug Absorption ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Water Soluble ◽  
Absorption Process ◽  
Innovative Strategies ◽  
The Poor ◽  
Water Soluble Drugs ◽  
Selection Of

In the last decade, there has been a mounting concern in lipid-based formulations to deliver water-soluble drugs. Lipid-based drug delivery systems are one of the budding and promising technologies designed to tackle the poor bioavailability problems. This chapter stresses the different mechanisms of lipophilic drug absorption along with its advantages and limitations. It points out the different mechanisms of how lipid-based excipients and the different formulations interact with the absorption process. This review provides a comprehensive summary about the lipid formulation classification scheme (LFCS), a guide for the selection of appropriate formulation and commonly used excipients for lipid-based formulations, along with the important factors to be considered in formulation design and excipient selection. This review also focuses on the formulation of solid lipid-based formulations, important evaluation aspects, and commercial formulations available for the purpose.

scholarly journals Poloxamer Hydrogels for Biomedical Applications

Pharmaceutics ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 671 ◽  
Author(s):  
Eleonora Russo ◽  
Carla Villa
Keyword(s):  
Drug Delivery ◽  
Ethylene Oxide ◽  
Propylene Oxide ◽  
Biomedical Application ◽  
Aqueous Environment ◽  
Molecular Weights ◽  
Long Time ◽  
Poly Ethylene Oxide ◽  
Poly Ethylene ◽  
Concentration Threshold

This review article focuses on thermoresponsive hydrogels consisting of poloxamers which are of high interest for biomedical application especially in drug delivery for ophthalmic, injectable, transdermal, and vaginal administration. These hydrogels remain fluid at room temperature but become more viscous gel once they are exposed to body temperature. In this way, the gelling system remains at the topical level for a long time and the drug release is controlled and prolonged. Poloxamers are synthetic triblock copolymers of poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO), also commercially known as Pluronics®, Synperonics® or Lutrol®. The different poloxamers cover a range of liquids, pastes, and solids, with molecular weights and ethylene oxide–propylene oxide weight ratios varying from 1100 to 14,000 and 1:9 to 8:2, respectively. Concentrated aqueous solutions of poloxamers form thermoreversible gels. In recent years this type of gel has arouse interest for tissue engineering. Finally, the use of poloxamers as biosurfactants is evaluated since they are able to form micelles in an aqueous environment above a concentration threshold known as critical micelle concentration (CMC). This property is exploited for drug delivery and different therapeutic applications.

Alteration of Actin Organization by Jaspamide Inhibits Ruffling, but not Phagocytosis or Oxidative Burst, in HL-60 Cells and Human Monocytes

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3994-4005 ◽  
Author(s):  
Ina Fabian ◽  
Drora Halperin ◽  
Smadar Lefter ◽  
Leonid Mittelman ◽  
Rom T. Altstock ◽  
...  
Keyword(s):  
Oxidative Burst ◽  
Phagocytic Activity ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Cyclic Peptide ◽  
De Novo ◽  
Human Monocytes ◽  
Actin Organization ◽  
Fibrous Network ◽  
Intracellular Movement

Abstract Jaspamide, a naturally occurring cyclic peptide isolated from the marine sponge Hemiastrella minor, has fungicidal and growth-inhibiting activities. Exposure of promyelocytic HL-60 cells and human monocytes to jaspamide induces a dramatic reorganization of actin from a typical fibrous network to focal aggregates. HL-60 cells exposed to 5 × 10−8 mol/L or 10−7 mol/L jaspamide exhibited a reduced proliferation rate. In addition, 10−7mol/L jaspamide induced maturation of HL-60 cells as indicated by the appearance of a lobulated nucleus in 55% ± 5% of the cells and immunophenotypic maturation of the leukemia cells (upregulation of CD16 and CD14 B antigens). Further characterization has shown that F-actin is aggregated both in HL-60 cells and in human monocytes exposed to 10−7 mol/L jaspamide. Well-spread cultured human monocytes contracted and adopted round shapes after treatment with jaspamide. Moreover, a dose-dependent increase in both total actin and de novo synthesized portions of the soluble actin was observed in jaspamide-treated HL-60 cells. Jaspamide treatment inhibits ruffling and intracellular movement in HL-60 cells and monocytes, but does not affect phagocytic activity or respiratory burst activity. The consequential effects of jaspamide-induced actin reorganization on ruffling, versus its negligible effect on phagocytosis and oxidative burst, may shed light on molecular mechanisms of actin involvement in these processes. Jaspamide disrupts the actin cytoskeleton of normal and malignant mammalian cells with no significant effect on phagocytic activity and may, therefore, be considered as a novel therapeutic agent.

scholarly journals Proteome and Phosphoproteome Analysis in TNF Long Term-Exposed Primary Human Monocytes

2019 ◽  
Vol 20 (5) ◽  
pp. 1241 ◽  
Author(s):  
Bastian Welz ◽  
Rolf Bikker ◽  
Johannes Junemann ◽  
Martin Christmann ◽  
Konstantin Neumann ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Human Monocytes ◽  
Binding Motifs ◽  
Enhancer Binding Protein ◽  
Induced Signal ◽  
Necrosis Factor ◽  
Viral Oncogene Homolog

To better understand the inflammation-associated mechanisms modulating and terminating tumor necrosis factor (TNF-)induced signal transduction and the development of TNF tolerance, we analyzed both the proteome and the phosphoproteome in TNF long term-incubated (i.e., 48 h) primary human monocytes using liquid chromatography-mass spectrometry. Our analyses revealed the presence of a defined set of proteins characterized by reproducible changes in expression and phosphorylation patterns in long term TNF-treated samples. In total, 148 proteins and 569 phosphopeptides were significantly regulated (103 proteins increased, 45 proteins decreased; 377 peptides with increased and 192 peptides with decreased phosphorylation). A variety of these proteins are associated with the non-canonical nuclear factor κB (NF-κB) pathway (nuclear factor κB (NFKB) 2, v-rel reticuloendotheliosis viral oncogene homolog (REL) B, indolamin-2,3-dioxygenase (IDO), kynureninase (KYNU)) or involved in the negative regulation of the canonical NF-κB system. Within the phosphopeptides, binding motifs for specific kinases were identified. Glycogen synthase kinase (GSK) 3 proved to be a promising candidate, since it targets NF-κB inhibiting factors, such as CCAAT/enhancer binding protein (C/EBP) β. Our experiments demonstrate that both proteome and phosphoproteome analysis can be effectively applied to study protein/phosphorylation patterns of primary monocytes. These results provide new regulatory candidates and evidence for a complex network of specific but synergistically acting/cooperating mechanisms enabling the affected cells to resist sustained TNF exposure and resulting in the resolution of inflammation.

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