Therapeutic Delivery of Targeted Nanoparticle Cannabinoid Equivalents
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE206164 | GEO | 2022/10/19
REPOSITORIES: GEO
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2022-05-01 | GSE188863 | GEO
Project description:We evaluated cutaneous contact hypersensitivity (CHS) in Cnr1-/-/Cnr2-/- animals using the obligate contact allergen 2,4-dinitrofluorobenzene (DNFB), which generates a specific cutaneous T-cell mediated allergic response upon repeated allergen contact. Allergic contact dermatitis affects about 5% of men and 11% of women in industrialized countries and is one of the leading causes for occupational diseases. In an animal model for cutaneous contact hypersensitivity we show that mice lacking both known cannabinoid receptors display exacerbated allergic inflammation. In contrast, fatty acid amide hydrolase deficient mice, which have increased levels of the endocannabinoid anandamide, displayed reduced allergic responses in the skin. Cannabinoid receptor antagonists exacerbated whereas receptor agonists attenuated allergic inflammation. These results demonstrate a protective role of the endocannabinoid system in contact allergy in the skin, and suggest a novel target for therapeutic intervention. Keywords: Strain (Wt versus Ko) and disease state (DNFB treated versus control).
2007-06-11 | GSE7694 | GEO
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2011-09-30 | E-GEOD-22949 | biostudies-arrayexpress
Project description:The United States is currently facing a severe opioid epidemic, therefore addressing how opioids induce rewarding behaviors could be key to a solution for this medical and societal crisis. Recently, the endogenous cannabinoid system has emerged as a hot topic in the study of opioid reward but relatively little is known about how chronic opioid exposure may affect this system. In the present study, we investigated how chronic morphine may modulate the endogenous cannabinoid system in the ventral tegmental area (VTA), a critical region in the mesolimbic reward circuitry. Our studies found that the VTA expresses 32 different proteins or genes related to the endogenous cannabinoid system; 3 of these proteins or genes were significantly affected after chronic morphine exposure. We also investigated the effects of acute and chronic morphine treatment on the production of the primary endocannabinoids, 2-Arachidonoylglycerol (2-AG) and anandamide (AEA), and identified that acute, but not chronic, morphine treatment significantly reduced AEA production in the VTA; 2-AG levels were unchanged in either condition. Lastly, our studies exhibited a systemic enhancement of 2-AG tone via inhibition of monoacylglycerol lipase (MAGL)-mediated degradation and the pharmacological activation of cannabinoid receptor 2 (CB2R) significantly suppressed chronic morphine-induced conditioned place preference. Taken together, our studies offer a broad picture of chronic morphine-induced alterations of the VTA endogenous cannabinoid system, provide several uncharacterized targets that could be used to develop novel therapies, and identify how manipulation of the endocannabinoid system can mitigate opioid reward to directly address the ongoing opioid epidemic.
2021-04-08 | PXD023096 | Pride
Project description:The endocannabinoid system plays important roles in the modulation of gastrointestinal motility and secretions. These effects are mainly mediated by the activation by the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) of CB1 receptors expressed on cholinergic neurons. Cannabis sativa extracts also perform these activities, through the detection of CB1 receptors by the phytocannabinoids they contain, in particular delta9-tetrahydrocannabinol.
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This research hypothesizes that drugs capable of inhibiting the biosynthetic and catabolic enzymes of endocannabinoids, of inhibiting the transmembrane transport of endocannabinoids or of allosterically modulating CB1 receptors induce important regulating effects of basal contractility and excitatory motor responses, induced by activation of neurons intramural cholinergics, of colonic circular smooth muscle.
The effects of drugs acting on CB receptors, endocannabinoid biosynthetic and catabolic enzymes and endocannabinoid membrane transporters on basal contractility or induced by neuronal activation of colonic preparations in vitro will be evaluated.
The study will enroll patients affected by colorectal cancer to undergo elective resective surgery at any stage, undergoing upfront surgery or after neo-adjuvant therapy with a therapeutic interval greater than 6 weeks. In the selected patients (see inclusion/exclusion criteria), a fresh sample of about 2.5 cm of healthy colon (healthy resection margin) will be taken, which will be taken in the operating room and sent to the laboratory for in vitro study.
Expected results: The study is expected to provide new evidence regarding the induction of pharmacological effects by allosteric receptor modulators of CB1 receptors, inhibitors of endocannabinoid biosynthetic and catabolic enzymes, and inhibitors of cannabinoid transporters in the human colon, which may open interesting perspectives regarding the development of new therapeutic strategies for the treatment of constipation, diarrhea and irritable bowel syndrome.
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Project description:Endocannabinoids belong to a diverse family of endogenous lipid bioregulators acting as physiological ligands of cannabinoid receptor type 1 and cannabinoid receptor type 2 in the central and peripheral nervous system. They are also present in nmol/l concentrations in human blood plasma; however, their association with possible molecular carriers remains poorly characterized. Here we report on the quantification of 46 endogenous molecular species from five major classes of endocannabinoids and endocannabinoid-related compounds in three lipoprotein fractions of human blood plasma: (VLDL), LDL, HDL, and in the plasma lipoproteinfree fraction. Although sizable quantities of endocannabinoid related molecules are associated with lipoproteins, we identified the lipoprotein-free fraction as a major carrier of endocannabinoids in blood circulation with the exception of 2-acylglycerols, which are markedly abundant in VLDL.
2015-03-11 | MTBLS163 | MetaboLights
Project description:We evaluated cutaneous contact hypersensitivity (CHS) in Cnr1-/-/Cnr2-/- animals using the obligate contact allergen 2,4-dinitrofluorobenzene (DNFB), which generates a specific cutaneous T-cell mediated allergic response upon repeated allergen contact. Allergic contact dermatitis affects about 5% of men and 11% of women in industrialized countries and is one of the leading causes for occupational diseases. In an animal model for cutaneous contact hypersensitivity we show that mice lacking both known cannabinoid receptors display exacerbated allergic inflammation. In contrast, fatty acid amide hydrolase deficient mice, which have increased levels of the endocannabinoid anandamide, displayed reduced allergic responses in the skin. Cannabinoid receptor antagonists exacerbated whereas receptor agonists attenuated allergic inflammation. These results demonstrate a protective role of the endocannabinoid system in contact allergy in the skin, and suggest a novel target for therapeutic intervention. Experiment Overall Design: Three wildtype mice (Wt) and three Cnr1-/-/Cnr2-/- (Ko) mice were used. Contact hypersensitivity was determined always at the right ears, which therefore were treated with DNFB (Tr). Left ears of mice were kept untreated and served as control ears (C). A total of 12 hybridizations were performed (2 strains x 2 treatments X 3 biological replicates) in this experiment.
2009-04-23 | E-GEOD-7694 | biostudies-arrayexpress
Project description:We tested the effects of isopropoyl dodecyl fluorophosphonate (IDFP) (10 mg/kg, i.p.), a pharmacological inhibitor of endocannabinoid degradation, on hepatic gene expression in mice. To determine if increased cannabinoid receptor 1 signaling is responsible for IDFP induced effects a subset of mice were pretreated with the cannabinoid receptor 1 antagonist (AM251) (10 mg/kg, i.p.).
2011-10-01 | GSE22949 | GEO
Project description:RNA interference (RNAi) holds tremendous potential as a therapeutic approach, especially in the treatment of malignant tumors. However, efficient and biocompatible delivery methods are needed for systemic delivery of siRNA. To achieve this goal, we have established a novel formulation of siRNA by incorporating it into reconstituted high density lipoprotein (rHDL) nanoparticles. Here, we demonstrate that rHDL nanoparticles facilitate highly efficient systemic delivery of siRNA in vivo, mediated by the scavenger receptor type B1 (SR-B1). Moreover, in therapeutic proof-of-concept studies, these nanoparticles were effective in targeting either signal transducer and activator of transcription 3 (STAT3) or focal adhesion kinase (FAK) expression in orthotopic mouse models of ovarian and colorectal cancer. These data indicate that an rHDL nanoparticle is a novel and highly efficient siRNA carrier, and therefore this novel technology could serve as the foundation for new cancer therapeutic approaches. To identify the role of STAT3 in ovarian cancer cell, we performed microarray after knocking down STAT3 in ovarican cancer cells (3 siCon and 3 siSTAT3).
2011-12-22 | E-GEOD-20597 | biostudies-arrayexpress
Project description:Interventions: Participants of this study will be receiving prescribed medicinal cannabis product/s via their treating clinician, as per standard of care. Enrolment into the study requires their clinician to consent participants and provide relevant medical history information, prescription information and updates and regular adverse event reporting throughout the study duration (12 months observation per participant).
Participants will be asked to complete a total of 14 questionnaires at set time points throughout the study. The study progress questionnaire including additional validated measures of health-related quality of life, medication adherence and patient reported change will be completed at enrolment, and months 1, 3, 6, 9 and 12 post-enrolment or until the participant ceases medicinal cannabis treatment (if prior to 12 months post-enrolment).
A short-form questionnaire focused on side effect reporting, current dose and changes to other concomitant medications will be completed at months 2, 4, 5, 7, 8, 10 and 11 post-enrolment or until the participant ceases medicinal cannabis treatment (if prior to 12 months post-enrolment).
It is anticipated that each questionnaire will take between 5-30 minutes to complete, requiring a total of 30 minutes maximum participation each month for the 12 months of the study.
Clinicians will be asked to complete the baseline enrolment form (10 minutes to complete) for each patient at study enrolment as well as adverse event monitoring questionnaires, each taking 5-10 minutes to complete every 3 months for the period that they have patients enrolled in the study.
Primary outcome(s): The type of medicinal cannabis product/s prescribed (including the formulation, prescribed dosage and underlying medical condition) as collected by study-specific questionnaires.
[Collected at baseline, and then monthly for a 12 month period post-enrolment. ];Number of adverse and serious adverse events experienced that are related to medicinal cannabis treatment, including but not limited to, dry mouth, somnolence and gastrointestinal upset, as measured by study-specific questionnaires. These will be captured by clinicians at clinical examinations and also reported by patients on a monthly basis using the safety reporting questionnaire. The safety reporting questionnaires being used are study specific. The clinician AE reporting questionnaire is based on the TGA recommended guidelines for AE reporting which conform to WHO grading and causality definitions. [Patient reported data collected at baseline, and then monthly for a 12 month period post-enrolment.
Clinician reported data collected at 3, 6, 9 and 12 months post-enrolment. ];Change to patient-reported concomitant medications (including opioid use) over the observational period using study-specific questionnaires. [Completed at baseline, and then monthly for 12 months post-enrolment. ]
Study Design: Purpose: Natural history;Duration: Longitudinal;Selection: Defined population;Timing: Prospective
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