scholarly journals Fabrication and Characterization of Paclitaxel and Resveratrol Loaded Soluplus Polymeric Nanoparticles for Improved BBB Penetration for Glioma Management

Polymers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 3210
Author(s):  
Talib Hussain ◽  
Sathishbabu Paranthaman ◽  
Syed Mohd Danish Rizvi ◽  
Afrasim Moin ◽  
Devegowda Vishakante Gowda ◽  
...  
Keyword(s):  
Polymeric Nanoparticles ◽  
C6 Glioma Cells ◽  
Brain Distribution ◽  
Distribution Study ◽  
Therapeutic Modalities ◽  
The Central Nervous System ◽  
Distribution Studies

Gliomas are one of the prominent cancers of the central nervous system with limited therapeutic modalities. The present investigation evaluated the synergistic effect of paclitaxel (PAX) and resveratrol (RESV)-loaded Soluplus polymeric nanoparticles (PNPs) against glioma cell lines along with in vivo pharmacokinetics and brain distribution study. PAX-RESV-loaded PNPs were prepared by the thin film hydration technique and optimized for different dependent and independent variables by using DoE (Design-Expert) software. The in vitro physiochemical characterization of prepared PAX-RESV-loaded PNPs exhibited appropriate particle size, PDI and % encapsulation efficiency. Cytotoxicity assay revealed that PTX-RESV loaded PNPs had a synergistic antitumor efficacy against C6 glioma cells compared with single and combined pure drugs. Finally, the pharmacokinetic and brain distribution studies in mice demonstrated that the PNPs significantly enhanced the bioavailability of PTX-RESV PNPs than pure PAX and RESV. Thus, the study concluded that PAX-RESV PNPs combination could significantly enhance anti-glioma activity, and this could be developed into a potential glioma treatment strategy.

DEVELOPMENT, CHARACTERIZATION AND BRAIN DISTRIBUTION STUDIES OF NANOSTRUCTURED LIPID CARRIER CONTAINING SAQUINAVIR MESYLATE FOR NASAL ADMINISTRATION

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (09) ◽  
pp. 38-47
Author(s):  
H. S. Mahajan ◽  
◽  
M. I. Patel
Keyword(s):  
Adverse Effect ◽  
Targeted Delivery ◽  
Entrapment Efficiency ◽  
Nasal Administration ◽  
Nanostructured Lipid Carrier ◽  
Brain Distribution ◽  
Scanning Calorimetry ◽  
Distribution Studies

The aim of the present study was to formulate saquinavir mesylate loaded nanostructured lipid carriers (SQVM-NLC) and evaluate its brain distribution after nasal administration. NLCs reveal some advantages for drug therapy over conventional carriers, including increased solubility, the ability to enhance storage stability, improved permeability and bioavailability, reduced adverse effect, prolonged half-life, and tissue-targeted delivery. SQVM-NLCs were prepared by hot high pressure homogenization and subsequent stabilization by lyophilization. QVM- NLC developed showed a particle with the size of 124.4 nm, polydispersity index of 0.267, entrapment efficiency of 73% and the zeta potential of -24.9 mV. The results from Scanning Electron Microscopy (SEM), powder X-ray diffraction (XRD)and differential scanning calorimetry (DSC) demonstrated that SQVM was present in NLC in an encapsulated molecule form. Mucosal toxicity study on sheep nasal mucosa showed no significant adverse effect of SQVMloaded NLC. SQVM-NLC showed slower release compared with saquinavir mesylate suspension in vitro. In vivo brain distribution studies demonstrated desired drug concentration in brain after intra nasal administration of SQVM-NLC than PDS. The results of the study also suggest that SQVM-NLC could be a promising drug delivery system for antiretroviral therapy.

scholarly journals Molecular and functional characterization of somatostatin-type signalling in a deuterostome invertebrate

Open Biology ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 200172
Author(s):  
Ya Zhang ◽  
Luis Alfonso Yañez Guerra ◽  
Michaela Egertová ◽  
Cleidiane G. Zampronio ◽  
Alexandra M. Jones ◽  
...  
Keyword(s):  
Functional Characterization ◽  
The Body ◽  
Pharmacological Characterization ◽  
Cardiac Stomach ◽  
Physiological Processes ◽  
Pharmacological Tests ◽  
The Central Nervous System

Somatostatin (SS) and allatostatin-C (ASTC) are structurally and evolutionarily related neuropeptides that act as inhibitory regulators of physiological processes in mammals and insects, respectively. Here, we report the first molecular and functional characterization of SS/ASTC-type signalling in a deuterostome invertebrate—the starfish Asterias rubens (phylum Echinodermata). Two SS/ASTC-type precursors were identified in A. rubens (ArSSP1 and ArSSP2) and the structures of neuropeptides derived from these proteins (ArSS1 and ArSS2) were analysed using mass spectrometry. Pharmacological characterization of three cloned A. rubens SS/ASTC-type receptors (ArSSR1–3) revealed that ArSS2, but not ArSS1, acts as a ligand for all three receptors. Analysis of ArSS2 expression in A. rubens using mRNA in situ hybridization and immunohistochemistry revealed stained cells/fibres in the central nervous system, the digestive system (e.g. cardiac stomach) and the body wall and its appendages (e.g. tube feet). Furthermore, in vitro pharmacological tests revealed that ArSS2 causes dose-dependent relaxation of tube foot and cardiac stomach preparations, while injection of ArSS2 in vivo causes partial eversion of the cardiac stomach. Our findings provide new insights into the molecular evolution of SS/ASTC-type signalling in the animal kingdom and reveal an ancient role of SS-type neuropeptides as inhibitory regulators of muscle contractility.

scholarly journals Andrographolide Induces Apoptosis of C6 Glioma Cells via the ERK-p53-Caspase 7-PARP Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Shih-Hung Yang ◽  
Seu-Mei Wang ◽  
Jhih-Pu Syu ◽  
Ying Chen ◽  
Sheng-De Wang ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Signaling Pathway ◽  
C6 Glioma Cells ◽  
Nuclear Staining ◽  
Anticancer Effects ◽  
Caspase 7 ◽  
The Central Nervous System ◽  
Induced Apoptosis

Background.Glioma is the most malignant tumor of the central nervous system. Efforts on the development of new chemotherapy are mandatory. Andrographolide (AND), a diterpenoid lactone isolated from theAndrographis paniculata, has been shown to have antitumor activities in several types of cancer cells. Whether AND can exert its antitumor activity in glioblastoma cells remains unknown. This study examined the anticancer effects of AND, bothin vitroandin vivo.Methods.Cell apoptosis was assayed by flow cytometry and nuclear staining. The signaling pathway for AND was determined by western blotting. The effects of AND on tumor growth was evaluated in a mouse model.Results and Conclusion. In vitro, with application of specific inhibitors and siRNA, AND-induced apoptosis was proven through ROS-ERK-P53-caspase 7-PARP signaling pathway.In vivo, AND significantly retarded tumor growth and caused regression of well-formed tumorsin vivo. Furthermore, AND did not induce apoptosis or activate ERK and p53 in primary cultured astrocyte cells, and it may serve as a potential therapeutic candidate for the treatment of glioma.

Rapid, Refined, and Robust Method for Expression, Purification, and Characterization of Recombinant Human Amyloid-beta M1-42

2019 ◽  
Author(s):  
Priya Prakash ◽  
Travis Lantz ◽  
Krupal P. Jethava ◽  
Gaurav Chopra
Keyword(s):  
Amyloid Beta ◽  
Western Blots ◽  
Force Microscopy ◽  
E Coli ◽  
Atomic Force ◽  
Set Up ◽  
Short Time

Amyloid plaques found in the brains of Alzheimer’s disease (AD) patients primarily consists of amyloid beta 1-42 (Ab42). Commercially, Ab42 is synthetized using peptide synthesizers. We describe a robust methodology for expression of recombinant human Ab(M1-42) in Rosetta(DE3)pLysS and BL21(DE3)pLysS competent E. coli with refined and rapid analytical purification techniques. The peptide is isolated and purified from the transformed cells using an optimized set-up for reverse-phase HPLC protocol, using commonly available C18 columns, yielding high amounts of peptide (~15-20 mg per 1 L culture) in a short time. The recombinant Ab(M1-42) forms characteristic aggregates similar to synthetic Ab42 aggregates as verified by western blots and atomic force microscopy to warrant future biological use. Our rapid, refined, and robust technique to purify human Ab(M1-42) can be used to synthesize chemical probes for several downstream in vitro and in vivo assays to facilitate AD research.

Radiosensitivity of glioma to Gamma Knife treatment enhanced in vitro and in vivo by RNA interfering Ku70 that is mediated by a recombinant adenovirus

2010 ◽  
Vol 113 (Special_Supplement) ◽  
pp. 228-235 ◽  
Author(s):  
Qiang Jia ◽  
Yanhe Li ◽  
Desheng Xu ◽  
Zhenjiang Li ◽  
Zhiyuan Zhang ◽  
...  
Keyword(s):  
Western Blot ◽  
Gamma Knife ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Glioma Cells ◽  
C6 Glioma ◽  
C6 Glioma Cells ◽  
C6 Cells

Object The authors sought to evaluate modification of the radiation response of C6 glioma cells in vitro and in vivo by inhibiting the expression of Ku70. To do so they investigated the effect of gene transfer involving a recombinant replication-defective adenovirus containing Ku70 short hairpin RNA (Ad-Ku70shRNA) combined with Gamma Knife treatment (GKT). Methods First, Ad-Ku70shRNA was transfected into C6 glioma cells and the expression of Ku70 was measured using Western blot analysis. In vitro, phenotypical changes in C6 cells, including proliferation, cell cycle modification, invasion ability, and apoptosis were evaluated using the MTT (3′(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) assay, Western blot analysis, and cell flow cytometry. In vivo, parental C6 cells transfected with Ad-Ku70shRNA were implanted stereotactically into the right caudate nucleus in Sprague-Dawley rats. After GKS, apoptosis was analyzed using the TUNEL (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling) method. The inhibitory effects on growth and invasion that were induced by expression of proliferating cell nuclear antigen and matrix metalloproteinase–9 were determined using immunohistochemical analyses. Results The expression of Ku70 was clearly inhibited in C6 cells after transfection with Ad-Ku70shRNA. In vitro following transfection, the C6 cells showed improved responses to GKT, including suppression of proliferation and invasion as well as an increased apoptosis index. In vivo following transfection of Ad-Ku70shRNA, the therapeutic efficacy of GKT in rats with C6 gliomas was greatly enhanced and survival times in these animals were prolonged. Conclusions Our data support the potential for downregulation of Ku70 expression in enhancing the radiosensitivity of gliomas. The findings of our study indicate that targeted gene therapy–mediated inactivation of Ku70 may represent a promising strategy in improving the radioresponsiveness of gliomas to GKT.

In vitro and in vivo characterization of graphene oxide coated porcine bone granules

Carbon ◽  
2016 ◽  
Vol 103 ◽  
pp. 291-298 ◽  
Author(s):  
Valeria Ettorre ◽  
Patrizia De Marco ◽  
Susi Zara ◽  
Vittoria Perrotti ◽  
Antonio Scarano ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
In Vivo Characterization

scholarly journals Functional identification of ygiP as a positive regulator of the ttdA-ttdB-ygjE operon

Microbiology ◽  
2006 ◽  
Vol 152 (7) ◽  
pp. 2129-2135 ◽  
Author(s):  
Taku Oshima ◽  
Francis Biville
Keyword(s):  
Functional Characterization ◽  
Anaerobic Growth ◽  
Functional Identification ◽  
New Members ◽  
E Coli ◽  
Inner Membrane Protein ◽  
Tartrate Dehydratase

Functional characterization of unknown genes is currently a major task in biology. The search for gene function involves a combination of various in silico, in vitro and in vivo approaches. Available knowledge from the study of more than 21 LysR-type regulators in Escherichia coli has facilitated the classification of new members of the family. From sequence similarities and its location on the E. coli chromosome, it is suggested that ygiP encodes a lysR regulator controlling the expression of a neighbouring operon; this operon encodes the two subunits of tartrate dehydratase (TtdA, TtdB) and YgiE, an integral inner-membrane protein possibly involved in tartrate uptake. Expression of tartrate dehydratase, which converts tartrate to oxaloacetate, is required for anaerobic growth on glycerol as carbon source in the presence of tartrate. Here, it has been demonstrated that disruption of ygiP, ttdA or ygjE abolishes tartrate-dependent anaerobic growth on glycerol. It has also been shown that tartrate-dependent induction of the ttdA-ttdB-ygjE operon requires a functional YgiP.

scholarly journals Functional Characterization of the mazEF Toxin-Antitoxin System in the Pathogenic Bacterium Agrobacterium tumefaciens

2021 ◽  
Vol 9 (5) ◽  
pp. 1107
Author(s):  
Wonho Choi ◽  
Yoshihiro Yamaguchi ◽  
Ji-Young Park ◽  
Sang-Hyun Park ◽  
Hyeok-Won Lee ◽  
...  
Keyword(s):  
Agrobacterium Tumefaciens ◽  
Physiological Function ◽  
Functional Characterization ◽  
Site Directed Mutagenesis ◽  
In Vitro Assays ◽  
Cell Growth Inhibition ◽  
The Right

Agrobacterium tumefaciens is a pathogen of various plants which transfers its own DNA (T-DNA) to the host plants. It is used for producing genetically modified plants with this ability. To control T-DNA transfer to the right place, toxin-antitoxin (TA) systems of A. tumefaciens were used to control the target site of transfer without any unintentional targeting. Here, we describe a toxin-antitoxin system, Atu0939 (mazE-at) and Atu0940 (mazF-at), in the chromosome of Agrobacterium tumefaciens. The toxin in the TA system has 33.3% identity and 45.5% similarity with MazF in Escherichia coli. The expression of MazF-at caused cell growth inhibition, while cells with MazF-at co-expressed with MazE-at grew normally. In vivo and in vitro assays revealed that MazF-at inhibited protein synthesis by decreasing the cellular mRNA stability. Moreover, the catalytic residue of MazF-at was determined to be the 24th glutamic acid using site-directed mutagenesis. From the results, we concluded that MazF-at is a type II toxin-antitoxin system and a ribosome-independent endoribonuclease. Here, we characterized a TA system in A. tumefaciens whose understanding might help to find its physiological function and to develop further applications.

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