Journal of pharmaceutics & pharmacology最新文献

{"title":"Effect of Centruroides antivenom on reversal of methamphetamine-induced hyperkinesis and hyperthermia in rats.","authors":"Pouran Malekzadeh, Jackie Hu, Alexander J Sandweiss, Nina Ameli, Philippe Bierny, Tally M Largent-Milnes, Todd W Vanderah, Farshad Shirazi","doi":"10.13188/2327-204X.1000020","DOIUrl":"https://doi.org/10.13188/2327-204X.1000020","url":null,"abstract":"Context\u0000Methamphetamine (MA) toxicity is a major health concern causing agitation, hyperkinesia, hyperthermia, and even death, affecting 24.7 million people worldwide. It has been observed that MA generates movement disorders in children similar to that of scorpion envenomation. Four cases have been reported where MA intoxication in children were both subjectively and objectively improved as indicated by the reversal of nystagmus and movement disorders following administration of Centruroides antivenom (AV) therapy.\u0000\u0000\u0000Objective\u0000Here, we aimed to demonstrate the reversal of MA induced movement disorders and hyperthermia by scorpion AV equine immune F(ab')2 in rats.\u0000\u0000\u0000Materials and Methods\u0000Baseline core temperature and locomotor activity in adult male Sprague-Dawley rats (200-220 g) were evaluated prior to acute administration of AV (20 mg/kg, intraperitoneally, i.p.) + MA (10 mg/kg, i.p.) or control. Core body temperature was reassessed 10, 50, and 80 min post injection while locomotor activity was reassessed 20-35 and 60-75 min post injection.\u0000\u0000\u0000Results\u0000At 20-35 min, Saline + MA and BSA + MA groups showed a significant increase in the number of fine events compared to their respective control groups Saline + Saline and BSA + Saline, which indicates an increase in paw movements of animals in situ (p = 0.008, p = 0.006, respectively). In contrast, AV + MA demonstrated a non-significant increase in fine activity compared to the control group AV + Saline). At 60-75 min, the AV + MA treatment group were less likely to engage in locomotor activity indicated by the significant decrease in exploratory events compared to BSA + MA control group (p = 0.041). No significant percent change in core body temperature was observed in the AV + MA treatment group compared to the control groups, AV + Saline and BSA + MA.\u0000\u0000\u0000Discussion\u0000Here, we provide evidence for some aspects of MA-induced hyperkinesia but not hyperthermia reversed by scorpion AV. Further preclinical studies involving adolescent rodents may be necessary to completely mimic the reversal of MA toxicity seen in children in the clinic.","PeriodicalId":89990,"journal":{"name":"Journal of pharmaceutics & pharmacology","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771266/pdf/nihms893095.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35754469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Inclusion Complexes of β-Cyclodextrin Derivatives Enhance Aqueous Solubility and Cellular Internalization of Paclitaxel: Preformulation and <i>In vitro</i> Assessments.","authors":"Milin Shah,&nbsp;Vatsal Shah,&nbsp;Anasuya Ghosh,&nbsp;Zheng Zhang,&nbsp;Tamara Minko","doi":"10.13188/2327-204X.1000011","DOIUrl":"https://doi.org/10.13188/2327-204X.1000011","url":null,"abstract":"<p><p>Drugs with low aqueous solubility and permeability possess substantial challenges in designing effective and safe formulations. Synergistic solubility and permeability enhancement in a simple formulation can increase bioavailability and efficacy of such drugs. To overcome limitations of the clinical formulation of Taxol®, Paclitaxel (PTX) was reformulated with various β-cyclodextrin (CD) derivatives suitable for parenteral administration. Results indicated that β-CDs can efficiently form complexes with PTX at lower molar ratios, enhance aqueous solubility up to 500 times and improved cellular internalization of PTX. All β-CD derivatives were found to be safe as excipient since none showed detectable signs of cyto-genotoxicity. As a result, the CD-PTX complexes significantly increased the cytotoxicity of the drug. The study concluded that CD-PTX formulations could substitute the current intravenous infusion of PTX obviating the use of non-inert excipient Cremophor EL.</p>","PeriodicalId":89990,"journal":{"name":"Journal of pharmaceutics & pharmacology","volume":"2 2","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2015-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.13188/2327-204X.1000011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33282488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling and Simulation of Intracellular Drug Transport and Disposition Pathways with Virtual Cell.","authors":"Jason Baik,&nbsp;Gus R Rosania","doi":"10.13188/2327-204X.1000004","DOIUrl":"https://doi.org/10.13188/2327-204X.1000004","url":null,"abstract":"<p><p>The development of computational approaches for modeling the spatiotemporal dynamics of intracellular, small molecule drug concentrations has become an increasingly important area of pharmaceutical research. For systems pharmacology, the system dynamics of subcellular transport can be coupled to downstream pharmacological effects on biochemical pathways that impact cell structure and function. Here, we demonstrate how a widely used systems biology modeling package - Virtual Cell - can also be used to model the intracellular, passive transport pathways of small druglike molecules. Using differential equations to represent passive drug transport across cellular membranes, spatiotemporal changes in the intracellular distribution and concentrations of exogenous chemical agents in specific subcellular organelles were simulated for weakly acidic, neutral, and basic molecules, as a function of the molecules' lipophilicity and ionization potentials. In addition, we simulated the transport properties of small molecule chemical agents in the presence of a homogenous extracellular concentration or a transcellular concentration gradient. We also simulated the effects of cell type-dependent variations in the intracellular microenvironments on the distribution and accumulation of small molecule chemical agents in different organelles over time, under influx and efflux conditions. Lastly, we simulated the transcellular transport of small molecule chemical agents, in the presence of different apical and basolateral microenvironments. By incorporating existing models of drug permeation and subcellular distribution, our results indicate that Virtual Cell can provide a user-friendly, open, online computational modeling platform for systems pharmacology and biopharmaceutics research, making mathematical models and simulation results accessible to a broad community of users, without requiring advanced computer programming knowledge.</p>","PeriodicalId":89990,"journal":{"name":"Journal of pharmaceutics & pharmacology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869409/pdf/nihms527973.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31976564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the Endocannabinoid System for Neuroprotection: A 19F-NMR Study of a Selective FAAH Inhibitor Binding with an Anandamide Carrier Protein, HSA","authors":"Jianqin Zhuang, De‐Ping Yang, X. Tian, S. Nikas, Rishi Sharma, J. Guo, A. Makriyannis","doi":"10.13188/2327-204X.1000002","DOIUrl":"https://doi.org/10.13188/2327-204X.1000002","url":null,"abstract":"Fatty acid amide hydrolase (FAAH), the enzyme involved in the inactivation of the endocannabinoid anandamide (AEA), is being considered as a therapeutic target for analgesia and neuroprotection. We have developed a brain permeable FAAH inhibitor, AM5206, which has served as a valuable pharmacological tool to explore neuroprotective effects of this class of compounds. In the present work, we characterized the interactions of AM5206 with a representative AEA carrier protein, human serum albumin (HSA), using 19F nuclear magnetic resonance (NMR) spectroscopy. Our data showed that as a drug carrier, albumin can significantly enhance the solubility of AM5206 in aqueous environment. Through a series of titration and competitive binding experiments, we also identified that AM5206 primarily binds to two distinct sites within HSA. Our results may provide insight into the mechanism of HSA-AM5206 interactions. The findings should also help in the development of suitable formulations of the lipophilic AM5206 and its congeners for their effective delivery to specific target sites in the brain.","PeriodicalId":89990,"journal":{"name":"Journal of pharmaceutics & pharmacology","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76858010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Glycogen Synthase Kinase 3 Beta in Neuroinflammation and Pain.","authors":"Dylan Warren Maixner,&nbsp;Han-Rong Weng","doi":"10.13188/2327-204X.1000001","DOIUrl":"https://doi.org/10.13188/2327-204X.1000001","url":null,"abstract":"<p><p>Neuroinflammation is a crucial mechanism related to many neurological diseases. Extensive studies in recent years have indicated that dysregulation of Glycogen Synthase Kinase 3 Beta (GSK3β) contributes to the development and progression of these disorders through regulating the neuroinflammation processes. Inhibitors of GSK3β have been shown to be beneficial in many neuroinflammatory disease models including Alzheimer's disease, multiple sclerosis and AIDS dem entia complex. Glial activation and elevated pro-inflammation cytokines (signs of neuroinflammation) in the spinal cord have been widely recognized as a pivotal mechanism underlying the development and maintenance of many types of pathological pain. The role of GSK3β in the pathogenesis of pain has recently emerged. In this review, we will first review the GSK3β structure, regulation, and mechanisms by which GSK3βregulates inflammation. We will then describe neuroinflammationin general and in specific types of neurological diseases and the potential beneficial effects induced by inhibiting GSK3β. Finally, we will provide new evidence linking aberrant levels of GSK3β in the development of pathological pain.</p>","PeriodicalId":89990,"journal":{"name":"Journal of pharmaceutics & pharmacology","volume":"1 1","pages":"001"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.13188/2327-204X.1000001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32742698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the Endocannabinoid System for Neuroprotection: A ¹⁹F-NMR Study of a Selective FAAH Inhibitor Binding with an Anandamide Carrier Protein, HSA.","authors":"Jianqin Zhuang, De-Ping Yang, Xiaoyu Tian, Spyros P Nikas, Rishi Sharma, Jason Jianxin Guo, Alexandros Makriyannis","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Fatty acid amide hydrolase (FAAH), the enzyme involved in the inactivation of the endocannabinoid anandamide (AEA), is being considered as a therapeutic target for analgesia and neuroprotection. We have developed a brain permeable FAAH inhibitor, AM5206, which has served as a valuable pharmacological tool to explore neuroprotective effects of this class of compounds. In the present work, we characterized the interactions of AM5206 with a representative AEA carrier protein, human serum albumin (HSA), using ¹⁹F nuclear magnetic resonance (NMR) spectroscopy. Our data showed that as a drug carrier, albumin can significantly enhance the solubility of AM5206 in aqueous environment. Through a series of titration and competitive binding experiments, we also identified that AM5206 primarily binds to two distinct sites within HSA. Our results may provide insight into the mechanism of HSA-AM5206 interactions. The findings should also help in the development of suitable formulations of the lipophilic AM5206 and its congeners for their effective delivery to specific target sites in the brain.</p>","PeriodicalId":89990,"journal":{"name":"Journal of pharmaceutics & pharmacology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32120892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}