Pub Date : 1900-01-01DOI: 10.1016/1043-6618(95)86446-6
G. Sgaragli, M. Valoti, M. Palmi, M. Frosini, M. Giovannini, L. Bianchi, L. Della Corte
{"title":"Rat tissue concentrations of chlorimipramine, chlorpromazine and their N-demethylated metabolites after a single oral dose of the parent compounds.","authors":"G. Sgaragli, M. Valoti, M. Palmi, M. Frosini, M. Giovannini, L. Bianchi, L. Della Corte","doi":"10.1016/1043-6618(95)86446-6","DOIUrl":"https://doi.org/10.1016/1043-6618(95)86446-6","url":null,"abstract":"","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121509275","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}
N. Gautam, H. Kushwaha, R. Pratap, Shio Kumar Singh
OBJECTIVES The aim of the study was to investigate the in-situ absorption kinetics, plasma protein binding and pharmacokinetic characteristics of a novel synthetic flavone derivative, S002-853, which shows pronounced antidiabetic and antidyslipidaemic activity. METHODS Quantification of S002-853 in plasma was performed by the LC-MS/MS method and in-situ sample analysis was carried out by the HPLC-UV method. KEY FINDINGS The absorption rate constant was 0.274/h in a mild alkaline environment, which S002-853 experiences in the intestine following oral dose administration. Plasma protein binding was found to be 26.37 +/- 2.58% at a concentration of 1 microg/ml. The pharmacokinetic parameters were determined in male rats after administration of a single 40 mg/kg oral dose and 10 mg/kg intravenous dose. The peak plasma concentration (C(max)) was found to be 60.93 ng/ml at 8 h after oral administration. Irregular concentration-time profiles with secondary peaks were observed after oral dose administration. The elimination half-life of the compound was 19.56 h and 16.30 h after oral and intravenous doses, respectively. Comparison of the AUC after oral and intravenous dosing of S002-853 indicates that only about 29.48% (bioavailability) of the oral dose reaches the systemic circulation. CONCLUSIONS In-situ study of S002-853 shows slow absorption from the gastrointestinal tract. S002-853 also shows low plasma protein binding. The pharmacokinetic parameters after oral and intravenous dose reveal low oral bioavailability and high mean residence time.
{"title":"In-situ absorption, protein binding and pharmacokinetic studies of S002-853, a novel antidiabetic and antidyslipidaemic flavone derivative in rats.","authors":"N. Gautam, H. Kushwaha, R. Pratap, Shio Kumar Singh","doi":"10.1211/jpp/62.05.0007","DOIUrl":"https://doi.org/10.1211/jpp/62.05.0007","url":null,"abstract":"OBJECTIVES\u0000The aim of the study was to investigate the in-situ absorption kinetics, plasma protein binding and pharmacokinetic characteristics of a novel synthetic flavone derivative, S002-853, which shows pronounced antidiabetic and antidyslipidaemic activity.\u0000\u0000\u0000METHODS\u0000Quantification of S002-853 in plasma was performed by the LC-MS/MS method and in-situ sample analysis was carried out by the HPLC-UV method.\u0000\u0000\u0000KEY FINDINGS\u0000The absorption rate constant was 0.274/h in a mild alkaline environment, which S002-853 experiences in the intestine following oral dose administration. Plasma protein binding was found to be 26.37 +/- 2.58% at a concentration of 1 microg/ml. The pharmacokinetic parameters were determined in male rats after administration of a single 40 mg/kg oral dose and 10 mg/kg intravenous dose. The peak plasma concentration (C(max)) was found to be 60.93 ng/ml at 8 h after oral administration. Irregular concentration-time profiles with secondary peaks were observed after oral dose administration. The elimination half-life of the compound was 19.56 h and 16.30 h after oral and intravenous doses, respectively. Comparison of the AUC after oral and intravenous dosing of S002-853 indicates that only about 29.48% (bioavailability) of the oral dose reaches the systemic circulation.\u0000\u0000\u0000CONCLUSIONS\u0000In-situ study of S002-853 shows slow absorption from the gastrointestinal tract. S002-853 also shows low plasma protein binding. The pharmacokinetic parameters after oral and intravenous dose reveal low oral bioavailability and high mean residence time.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134277340","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}
P. Marini, L. Romanelli, D. Valeri, P. Tucci, P. Valeri, M. Palmery
OBJECTIVES In isolated guinea-pig ileum, the mu-opioid acute withdrawal response is under control of several neuronal systems, including the kappa-opioid and the A(1)-adenosine systems, which are involved in the mu-withdrawal response inhibitory control. After mu-opioid system stimulation, indirect activation of both kappa-opioid and A(1)-adenosine systems is prevented by the peptide cholecystokinin-8 (CCk-8). Guinea-pig ileum exposed to A(1)-adenosine agonist (CPA), shows a withdrawal contracture precipitated by the A(1)-adenosine antagonist (CPT). We investigated this response. METHODS We investigated the involvement of the opioid system in the A(1)-adenosine acute withdrawal response in guinea-pig ileum, the potential induced cross-dependence between the A(1) and the opioid system and also the interaction between the CCk-8 and A(1) systems. KEY FINDINGS We found that in the guinea-pig ileum preparation exposed to CPA, mu- and kappa-opioid antagonists increased the withdrawal response to CPT. Tissues exposed to CPA showed a contractile response to the opioid receptor antagonist naloxone only after complete removal of the A(1)-agonist. In the presence of CPA, the response to CCk-8 was inhibited while a significant increase in CPT response intensity was observed. CONCLUSIONS In guinea-pig ileum, stimulation of the A(1) system indirectly activates both mu- and kappa-opioid systems; this indirect activation is significantly, albeit not completely, antagonised by CCk-8. Cross dependence between A(1) and opioid systems was also observed.
{"title":"Acute withdrawal induced by adenosine A-receptor activation in isolated guinea-pig ileum: role of opioid receptors and effect of cholecystokinin.","authors":"P. Marini, L. Romanelli, D. Valeri, P. Tucci, P. Valeri, M. Palmery","doi":"10.1211/jpp/62.05.0010","DOIUrl":"https://doi.org/10.1211/jpp/62.05.0010","url":null,"abstract":"OBJECTIVES\u0000In isolated guinea-pig ileum, the mu-opioid acute withdrawal response is under control of several neuronal systems, including the kappa-opioid and the A(1)-adenosine systems, which are involved in the mu-withdrawal response inhibitory control. After mu-opioid system stimulation, indirect activation of both kappa-opioid and A(1)-adenosine systems is prevented by the peptide cholecystokinin-8 (CCk-8). Guinea-pig ileum exposed to A(1)-adenosine agonist (CPA), shows a withdrawal contracture precipitated by the A(1)-adenosine antagonist (CPT). We investigated this response.\u0000\u0000\u0000METHODS\u0000We investigated the involvement of the opioid system in the A(1)-adenosine acute withdrawal response in guinea-pig ileum, the potential induced cross-dependence between the A(1) and the opioid system and also the interaction between the CCk-8 and A(1) systems.\u0000\u0000\u0000KEY FINDINGS\u0000We found that in the guinea-pig ileum preparation exposed to CPA, mu- and kappa-opioid antagonists increased the withdrawal response to CPT. Tissues exposed to CPA showed a contractile response to the opioid receptor antagonist naloxone only after complete removal of the A(1)-agonist. In the presence of CPA, the response to CCk-8 was inhibited while a significant increase in CPT response intensity was observed.\u0000\u0000\u0000CONCLUSIONS\u0000In guinea-pig ileum, stimulation of the A(1) system indirectly activates both mu- and kappa-opioid systems; this indirect activation is significantly, albeit not completely, antagonised by CCk-8. Cross dependence between A(1) and opioid systems was also observed.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"62 5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131294903","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}
Pub Date : 1900-01-01DOI: 10.4135/9781446247501.n3081
N. Burman, E. Taylor
{"title":"Potable water.","authors":"N. Burman, E. Taylor","doi":"10.4135/9781446247501.n3081","DOIUrl":"https://doi.org/10.4135/9781446247501.n3081","url":null,"abstract":"","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"102 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116472188","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}
Pub Date : 1900-01-01DOI: 10.3109/03639048809152005
D. Wong, M. Waring, P. Wright, M. Aulton
During the deformation of single crystals of alpha-lactose monohydrate and anhydrous alpha-lactose in a crushing strength rig, their acoustic activity was monitored using a portable activity meter. The acoustic parameters measured were the average signal level (ASL), count rates and total acoustic counts. Both types of lactose, even though deformed by fragmentation, differed fundamentally in the degree and nature of this fragmentation. Close correlation was observed between the ASL, count rate profiles and the force-displacement profiles. The monohydrate form is acoustically more active than the anhydrous form during deformation. Small internal fractures which were neither visually observed nor detected in the force-displacement profiles (in particular the anhydrous alpha-lactose) were detected by monitoring the acoustic signals during the deformation of these crystals. This work illustrates the potential of using the acoustic emission technique as an aid in the assessment of the deformation characteristics of pharmaceutical materials during single crystal compression studies.
{"title":"Acoustic emission during the deformation of alpha-lactose monohydrate and anhydrous alpha-lactose monocrystals.","authors":"D. Wong, M. Waring, P. Wright, M. Aulton","doi":"10.3109/03639048809152005","DOIUrl":"https://doi.org/10.3109/03639048809152005","url":null,"abstract":"During the deformation of single crystals of alpha-lactose monohydrate and anhydrous alpha-lactose in a crushing strength rig, their acoustic activity was monitored using a portable activity meter. The acoustic parameters measured were the average signal level (ASL), count rates and total acoustic counts. Both types of lactose, even though deformed by fragmentation, differed fundamentally in the degree and nature of this fragmentation. Close correlation was observed between the ASL, count rate profiles and the force-displacement profiles. The monohydrate form is acoustically more active than the anhydrous form during deformation. Small internal fractures which were neither visually observed nor detected in the force-displacement profiles (in particular the anhydrous alpha-lactose) were detected by monitoring the acoustic signals during the deformation of these crystals. This work illustrates the potential of using the acoustic emission technique as an aid in the assessment of the deformation characteristics of pharmaceutical materials during single crystal compression studies.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114959823","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}
M. Nagata, Y. Hidaka, M. Hidaka, Y. Kawano, T. Iwakiri, M. Okumura, K. Arimori
OBJECTIVES In cancer chemotherapy for hepatocellular carcinoma, 5-fluorouracil is widely used and has typically been given by intrahepatic arterial (i.a.) infusion to increase treatment efficacy and reduce systemic toxicity. 5-Fluorouracil is eliminated primarily by the liver and so the hepatic first-pass effect after intrahepatic arterial administration of 5-fluorouracil may be lower in patients with hepatic failure, and systemic toxicity may not be reduced. In this study, we have investigated the effect of acute hepatic failure on the first-pass effect of 5-fluorouracil in rats. METHODS Experimental acute hepatic failure was induced by treatment with carbon tetrachloride (CCl4). 5-Fluorouracil was infused for 15 min into the hepatic artery or the saphenous vein of rats at a dose of 1.25 mg/kg. KEY FINDINGS Hepatic availability in 50% CCl4-treated (severe hepatic failure) rats was higher than in controls. CONCLUSIONS The hepatic first-pass effect after intrahepatic arterial administration of 5-fluorouracil was lower in severe hepatic failure. Therefore, the reducing effect of the systemic toxicity after intrahepatic arterial administration may be lower in severe hepatic failure.
{"title":"Effect of acute hepatic failure on the hepatic first-pass effect of 5-fluorouracil in rats.","authors":"M. Nagata, Y. Hidaka, M. Hidaka, Y. Kawano, T. Iwakiri, M. Okumura, K. Arimori","doi":"10.1211/jpp/62.05.0006","DOIUrl":"https://doi.org/10.1211/jpp/62.05.0006","url":null,"abstract":"OBJECTIVES\u0000In cancer chemotherapy for hepatocellular carcinoma, 5-fluorouracil is widely used and has typically been given by intrahepatic arterial (i.a.) infusion to increase treatment efficacy and reduce systemic toxicity. 5-Fluorouracil is eliminated primarily by the liver and so the hepatic first-pass effect after intrahepatic arterial administration of 5-fluorouracil may be lower in patients with hepatic failure, and systemic toxicity may not be reduced. In this study, we have investigated the effect of acute hepatic failure on the first-pass effect of 5-fluorouracil in rats.\u0000\u0000\u0000METHODS\u0000Experimental acute hepatic failure was induced by treatment with carbon tetrachloride (CCl4). 5-Fluorouracil was infused for 15 min into the hepatic artery or the saphenous vein of rats at a dose of 1.25 mg/kg.\u0000\u0000\u0000KEY FINDINGS\u0000Hepatic availability in 50% CCl4-treated (severe hepatic failure) rats was higher than in controls.\u0000\u0000\u0000CONCLUSIONS\u0000The hepatic first-pass effect after intrahepatic arterial administration of 5-fluorouracil was lower in severe hepatic failure. Therefore, the reducing effect of the systemic toxicity after intrahepatic arterial administration may be lower in severe hepatic failure.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"62 5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129398939","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}
F. Bigucci, B. Luppi, L. Monaco, T. Cerchiara, V. Zecchi
OBJECTIVES The aim of this study was to describe a colon-specific delivery system based on pectin hydrogels formed by complexation with chitosan. METHODS Hydrogels were prepared at different weight ratios (4:1, 7:1, 10:1; pectin/chitosan), loaded with vancomycin hydrochloride (2:1, 4:1; polymer/drug weight ratio) and collected by spray-drying. The microspheres obtained were characterized in terms of morphology, swelling behaviour, mucoadhesive properties and drug loading efficiency. The influence of different pectin/chitosan hydrogels on the release behaviour of microspheres at pH 2.0, 5.5 and 7.4 were evaluated in vitro with and without pectinolytic enzyme. KEY FINDINGS The results showed that water uptake was increased by raising the environmental pH (from 2.0 to 7.4) and the pectin/chitosan weight ratio, while drug availability was increased by raising the environmental pH (from 2.0 to 7.4) and decreased by raising the pectin/chitosan weight ratio. In the presence of pectinase, the glycoside bonds of pectin were degraded and a considerable amount of drug was released in a short time. CONCLUSIONS This study suggested that pectin/chitosan microspheres were able to limit the release of vancomycin under acidic conditions and release it under simulated colonic conditions, confirming their potential for a colon-specific drug delivery system.
{"title":"Pectin-based microspheres for colon-specific delivery of vancomycin.","authors":"F. Bigucci, B. Luppi, L. Monaco, T. Cerchiara, V. Zecchi","doi":"10.1211/jpp/61.01.0006","DOIUrl":"https://doi.org/10.1211/jpp/61.01.0006","url":null,"abstract":"OBJECTIVES\u0000The aim of this study was to describe a colon-specific delivery system based on pectin hydrogels formed by complexation with chitosan.\u0000\u0000\u0000METHODS\u0000Hydrogels were prepared at different weight ratios (4:1, 7:1, 10:1; pectin/chitosan), loaded with vancomycin hydrochloride (2:1, 4:1; polymer/drug weight ratio) and collected by spray-drying. The microspheres obtained were characterized in terms of morphology, swelling behaviour, mucoadhesive properties and drug loading efficiency. The influence of different pectin/chitosan hydrogels on the release behaviour of microspheres at pH 2.0, 5.5 and 7.4 were evaluated in vitro with and without pectinolytic enzyme.\u0000\u0000\u0000KEY FINDINGS\u0000The results showed that water uptake was increased by raising the environmental pH (from 2.0 to 7.4) and the pectin/chitosan weight ratio, while drug availability was increased by raising the environmental pH (from 2.0 to 7.4) and decreased by raising the pectin/chitosan weight ratio. In the presence of pectinase, the glycoside bonds of pectin were degraded and a considerable amount of drug was released in a short time.\u0000\u0000\u0000CONCLUSIONS\u0000This study suggested that pectin/chitosan microspheres were able to limit the release of vancomycin under acidic conditions and release it under simulated colonic conditions, confirming their potential for a colon-specific drug delivery system.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121080794","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}
N. Nishimura, Tomichika Uemura, K. Iwamoto, K. Naora
OBJECTIVES This study was designed to investigate the effects of Sho-saiko-to (Xiao Chai Hu Tang), a Chinese traditional medicine, on the membrane permeability of tolbutamide in the intestinal tract. We carried out an in-situ loop study with rat jejunum and a transport study with Caco-2 cell monolayers. METHODS In the in-situ loop study, absorption clearance of tolbutamide was estimated from the drug concentrations in the loop and plasma. The apical-to-basolateral and basolateral-to-apical transport of tolbutamide and d-mannitol, a paracellular transport marker, was assessed using Caco-2 cell monolayers cultured on a polycarbonate membrane. KEY FINDINGS The absorption clearance of tolbutamide was enhanced by a concomitant dose of Sho-saiko-to over 10 min in the rat in-situ loop. Sho-saiko-to increased the apical-to-basolateral transport of tolbutamide, whereas the basolateral-to-apical transport of this drug was reduced by Sho-saiko-to. On the other hand, in both directions the P(app) of d-mannitol was reduced by the presence of Sho-saiko-to. Furthermore, the apical-to-basolateral transport of tolbutamide in ATP-depleted Caco-2 cells was diminished by Sho-saiko-to. These findings suggest that Sho-saiko-to can facilitate the epithelial membrane permeability of tolbutamide across the rat jejunum in-situ and Caco-2 cell monolayers. Since Sho-saiko-to suppressed the passive transport of tolbutamide from the apical-to-basolateral side, enhanced permeability may be related to effects of Sho-saiko-to on the energy-dependent transport of tolbutamide in the intestine. CONCLUSIONS Our findings suggest that Sho-saiko-to might facilitate the energy-dependent transport of tolbutamide across the rat jejunum in-situ and Caco-2 cell monolayers.
{"title":"Change in tolbutamide permeability in rat jejunum and Caco-2 cells by Sho-saiko-to (Xiao Chai Hu Tang), a Chinese traditional medicine.","authors":"N. Nishimura, Tomichika Uemura, K. Iwamoto, K. Naora","doi":"10.1211/jpp/62.05.0014","DOIUrl":"https://doi.org/10.1211/jpp/62.05.0014","url":null,"abstract":"OBJECTIVES\u0000This study was designed to investigate the effects of Sho-saiko-to (Xiao Chai Hu Tang), a Chinese traditional medicine, on the membrane permeability of tolbutamide in the intestinal tract. We carried out an in-situ loop study with rat jejunum and a transport study with Caco-2 cell monolayers.\u0000\u0000\u0000METHODS\u0000In the in-situ loop study, absorption clearance of tolbutamide was estimated from the drug concentrations in the loop and plasma. The apical-to-basolateral and basolateral-to-apical transport of tolbutamide and d-mannitol, a paracellular transport marker, was assessed using Caco-2 cell monolayers cultured on a polycarbonate membrane.\u0000\u0000\u0000KEY FINDINGS\u0000The absorption clearance of tolbutamide was enhanced by a concomitant dose of Sho-saiko-to over 10 min in the rat in-situ loop. Sho-saiko-to increased the apical-to-basolateral transport of tolbutamide, whereas the basolateral-to-apical transport of this drug was reduced by Sho-saiko-to. On the other hand, in both directions the P(app) of d-mannitol was reduced by the presence of Sho-saiko-to. Furthermore, the apical-to-basolateral transport of tolbutamide in ATP-depleted Caco-2 cells was diminished by Sho-saiko-to. These findings suggest that Sho-saiko-to can facilitate the epithelial membrane permeability of tolbutamide across the rat jejunum in-situ and Caco-2 cell monolayers. Since Sho-saiko-to suppressed the passive transport of tolbutamide from the apical-to-basolateral side, enhanced permeability may be related to effects of Sho-saiko-to on the energy-dependent transport of tolbutamide in the intestine.\u0000\u0000\u0000CONCLUSIONS\u0000Our findings suggest that Sho-saiko-to might facilitate the energy-dependent transport of tolbutamide across the rat jejunum in-situ and Caco-2 cell monolayers.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123886026","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}
G. Cirillo, O. I. Parisi, M. Curcio, F. Puoci, F. Iemma, U. G. Spizzirri, N. Picci
OBJECTIVES The aim was to synthesize molecularly imprinted polymers (MIPs) with high recognition properties towards glycyrrhizic acid and to evaluate the performance of these materials to act as base excipients in glycyrrhizic acid sustained release in gastrointestinal simulating fluids. METHODS MIPs were synthesized using methacrylic acid (MAA) as acidic, 2-(dimethylamino)ethyl methacrylate (DMAEMA) as basic, and 2-hydroxyethylmethacrylate (HEMA) as neutral functional monomers, while ethylene glycol dimethacrylate (EGDMA) was chosen as a crosslinking agent. The imprinting effect was evaluated by binding experiments using glycyrrhizic acid and glycyrrhetic acid (analogue molecule) solutions and in-vitro release studies were performed in gastrointestinal simulating fluids. KEY FINDINGS Good recognition and selectivity properties were found in all the synthesized materials in both ethanol and ethanol-water mixture. The release from non-imprinted polymers was indeed higher at acidic pH, while a slower release was observed in MIPs' case, because of the presence of imprinted cavities in the polymeric structure. The stronger capacity of MAA to interact by hydrogen bonds with the template makes MAA-containing MIPs the most effective materials in both rebinding and release experiments. CONCLUSIONS The release tests confirm the applicability of imprinted polymer for glycyrrhizic acid sustained release in gastrointestinal simulating fluids.
{"title":"Molecularly imprinted polymers as drug delivery systems for the sustained release of glycyrrhizic acid.","authors":"G. Cirillo, O. I. Parisi, M. Curcio, F. Puoci, F. Iemma, U. G. Spizzirri, N. Picci","doi":"10.1211/jpp/62.05.0003","DOIUrl":"https://doi.org/10.1211/jpp/62.05.0003","url":null,"abstract":"OBJECTIVES\u0000The aim was to synthesize molecularly imprinted polymers (MIPs) with high recognition properties towards glycyrrhizic acid and to evaluate the performance of these materials to act as base excipients in glycyrrhizic acid sustained release in gastrointestinal simulating fluids.\u0000\u0000\u0000METHODS\u0000MIPs were synthesized using methacrylic acid (MAA) as acidic, 2-(dimethylamino)ethyl methacrylate (DMAEMA) as basic, and 2-hydroxyethylmethacrylate (HEMA) as neutral functional monomers, while ethylene glycol dimethacrylate (EGDMA) was chosen as a crosslinking agent. The imprinting effect was evaluated by binding experiments using glycyrrhizic acid and glycyrrhetic acid (analogue molecule) solutions and in-vitro release studies were performed in gastrointestinal simulating fluids.\u0000\u0000\u0000KEY FINDINGS\u0000Good recognition and selectivity properties were found in all the synthesized materials in both ethanol and ethanol-water mixture. The release from non-imprinted polymers was indeed higher at acidic pH, while a slower release was observed in MIPs' case, because of the presence of imprinted cavities in the polymeric structure. The stronger capacity of MAA to interact by hydrogen bonds with the template makes MAA-containing MIPs the most effective materials in both rebinding and release experiments.\u0000\u0000\u0000CONCLUSIONS\u0000The release tests confirm the applicability of imprinted polymer for glycyrrhizic acid sustained release in gastrointestinal simulating fluids.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122311905","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}
N. Wittschier, C. Lengsfeld, S. Vorthems, U. Stratmann, J. Ernst, E. Verspohl, A. Hensel
Anti-adhesive compounds are potential prophylactic tools in alternative treatment regimes against bacterial infection, as bacterial adhesion is commonly mediated by carbohydrate-protein interactions between surface adhesions of microorganisms and the host cell. The use of exogenous polyvalent, high-molecular carbohydrates and tannin-like plant-derived compounds should antagonize the adhesive interaction. A range of carbohydrates and carbohydrate- and proanthocyanidin-enriched plant extracts were screened for potential anti-adhesive effects against Helicobacter pylori, Campylobacter jejuni, Porphyromonas gingivalis and Candida albicans in different in-situ assays on primary tissue. The adhesion of H. pylori on human stomach tissue was effectively blocked by glucuronic acid-enriched polysaccharides from immature okra fruits (Abelmoschus esculentus). These compounds also had strong in-vitro effects against C. jejuni (inhibition up to 80%), but were ineffective in an in-vivo study in infected chicken broilers due to metabolism in the gastrointestinal system. Polysaccharides from Glycyrrhizia glabra, also enriched with glucuronic acid, showed strong anti-adhesive properties against H. pylori and P. gingivalis (inhibition 60-70%). Pelargonium sidoides extract, containing mainly polymeric proanthocyanidins, was effective against H. pylori in a dose-dependent manner. Due to the multifunctional adhesive strategy of C. albicans, no effective compounds were detected against this yeast. Structure-activity relationships are presented and the potential in-vivo use of carbohydrate-based anti-adhesives is discussed.
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