Journal of Pharmacy and Pharmacology
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Influence of penetration enhancers on topical delivery of 5-aminolevulinic acid from bioadhesive patches Abstract
Objectives
The inclusion of chemical penetration enhancers in a novel patch-based system for the delivery of 5-aminolevulinic acid (ALA) was examined in vitro and in vivo. Poor penetration of ALA has been implicated as the primary factor for low response rates achieved with topical ALA-based photodynamic therapy of thicker neoplastic lesions, such as nodular basal cell carcinomas.
Methods
Several chemical permeation enhancers (dimethylsulfoxide, Labrafac CC, Labrafac PG and Labrafil M1944CS) were incorporated into bioadhesive patches tailored to deliver 19 mg ALA/cm2.
Key findings
In-vitro depth penetration studies into excised porcine skin showed that high concentrations of ALA (>9 μmol/cm3) could be delivered to a depth of 1.875 mm. However, inclusion of permeation enhancers did not significantly increase ALA delivery, relative to the control (P > 0.05). In-vivo studies were in strong agreement with in-vitro results, with formulations containing chemical enhancers showing no improvement in delivery compared with the control.
Conclusions
The patches designed in this work are suited to defineable ALA delivery without the need to immobilise patients for up to 6 h, as is common with the cream-under-occlusion approach. Overall, permeation enhancers were not found to markedly enhance the topical delivery of ALA. However, chemical penetration enhancers may have a greater effect on the delivery of more lipophilic ALA prodrugs, which are thought to primarily permeate the stratum corneum via the intercellular pathway.
Journal of Pharmacy and Pharmacology - Tập 62 Số 6 - Trang 685-695 - 2010
Comparative effects of leukotriene B4, prostaglandins I2 and E2, 6-keto-PGF1α, thromboxane B2 and histamine on selected smooth muscle preparations
Journal of Pharmacy and Pharmacology - Tập 33 Số 1 - Trang 466-468 - 1981
Chemometric evaluation of hypericin and related phytochemicals in 17 <i>in vitro</i> cultured <i>Hypericum</i> species, hairy root cultures and hairy root-derived transgenic plants Abstract
Objectives
The objective of this study was to ascertain the presence and correlations among eight important secondary metabolites viz. hypericin, pseudohypericin, emodin, hyperforin, rutin, hyperoside, quercetin and quercitrin in different organs of 17 in vitro cultured Hypericum species, along with H. tomentosum and H. tetrapterum hairy root cultures, and hairy root-derived transgenic plants of H. tomentosum.
Methods
Samples were extracted and analysed by LC-MS. The LC-MS data were subjected to chemometric evaluations for metabolite profiling and correlating the phytochemical compositions in different samples.
Key findings
Hypericin, pseudohypericin and their proposed precursor emodin were detected in various levels in the leaves of eight Hypericum species. The highest content of hypericins and emodin was found in H. tetrapterum, which contains the studied secondary metabolites in all plant organs. A significant positive correlation between hypericins and emodin was observed both by principal component analysis (PCA) and multidimensional scaling (MDS), indicating the role of emodin as a possible precursor in the biosynthetic pathway of hypericins. Flavonoids were found in all tested plant organs except roots of H. pulchrum. The hairy roots lacked hypericin, pseudohypericin, emodin, hyperforin and rutin. However, the hairy root-derived transgenic plants showed a significant increase in flavonoids.
Conclusions
This study broadens knowledge about the phytochemical composition of selected in vitro cultured Hypericum species, compared to that of hairy root cultures and hairy root-derived transgenic plants.
Journal of Pharmacy and Pharmacology - Tập 71 Số 1 - Trang 46-57 - 2019
Isolation and characterisation of hepatotoxins from Penicillium rubrum
Journal of Pharmacy and Pharmacology - Tập 18 Số 7 - Trang 471-473 - 1966
Effects of khellin on contractile responses and 45Ca2+ movements in rat isolated aorta Abstract
The effects of khellin on contractile responses and 45Ca2+ flux have been studied in rat isolated aortae. Khellin (10−5- 3.2 times 10−4M) produced a concentration-dependent inhibition of noradrenaline (10−6 M) and high K+ (80 mM)-induced contractions. At 3.2 times 10−4 M, khellin increased cAMP levels and reduced 45Ca2+ influx in resting tissues and in tissues stimulated by noradrenaline (10−5 M) and high K+ without affecting basal 45Ca2+ efflux or noradrenaline induced 45Ca2+ efflux. It is concluded that in rat isolated aorta, khellin caused a non-specific inhibition of Ca2+ influx but may also exhibit intracellular actions, thus decreasing the availability of Ca2+ required for activation. One or more of these mechanisms may be related to an increase in intracellular cAMP levels.
Journal of Pharmacy and Pharmacology - Tập 43 Số 1 - Trang 46-48 - 1991
Effect of the Chloroform Extract of <i>Tanacetum vulgare</i> and one of its Active Principles, Parthenolide, on Experimental Gastric Ulcer in Rats Abstract
This study examines the anti-ulcerogenic activity of a chloroform extract of Tanacetum vulgare and purified parthenolide, the major sesquiterpene lactone found in the extract.
Gastric ulcers induced by oral administration of absolute ethanol to rats were reduced dose-dependently by oral pretreatment of animals with the chloroform extract (2.5–80 mg kg−1) or parthenolide (5–40 mgkg−1). When administered 30 min before challenge with the alcohol the protection ranged between 34 and 100% for the extract and 27 and 100% for parthenolide. When the products were administered orally 24h before treatment with ethanol, 40 mg kg−1 of the extract and of the lactone reduced the mean ulcer index from 4.8 ± 0.3 for control animals to 1.4 ± 0.2 and 0.5 ± 0.1, respectively. The products also prevented alcohol-induced reduction of the number of sulphydryl groups within the gastric mucosa (50.6 ± 2.3 μg (mg protein)−1 for normal animals compared with 17.7 ± 3.0 μg (mg protein)−1 for alcohol-treated animals). Administration of the extract (80 mg kg−1) or parthenolide (40 mg kg−1) 24h before ethanol treatment restored the numbers of mucosal -SH groups to values near those found for normal animals.
These results suggest that the products assayed, in particular parthenolide, might find therapeutic application, although further work is required to establish their profit/risk ratio.
Journal of Pharmacy and Pharmacology - Tập 51 Số 2 - Trang 215-219 - 1999
Anti-inflammatory Effects of South American <i>Tanacetum vulgare</i> Abstract
In recent years the role of phenolic compounds and sesquiterpene lactones, particularly parthenolide, in the anti-migraine and anti-inflammatory effects of Tanacetum parthenium (Asteraceae) has attracted much attention. However, the closely-related cosmopolitan species T. vulgare has remained outside the mainstream of research in this field.
After treating the aerial parts of T. vulgare with dichloromethane and methanol, and applying conventional column and thin-layer chromatographic techniques, it was possible to isolate from the moderately lipophilic fractions the principles responsible for the anti-inflammatory activity of this plant against the mouse-ear oedema induced by 12-O-tetradecanoylphorbol 13-acetate. These were identified by ultraviolet and nuclear magnetic resonance spectroscopy as parthenolide (93% oedema inhibition at 0.5 mg/ear, ID50 (dose of drug inhibiting the oedema by 50%) = 0.18 μmol/ear) and the methoxyflavones jaceosidin (80% oedema inhibition at 0.5 mg/ear, ID50 = 0.50 μmol/ear), eupatorin, chrysoeriol and diosmetin.
Because in molar terms the potency of parthenolide was nearly three times greater than that of the most active of the flavones and because it is obtained from the plant in considerably larger amounts, the flavonoids must only be partially responsible, and to a minor extent, for the observed in-vivo anti-inflammatory local effect.
Journal of Pharmacy and Pharmacology - Tập 50 Số 9 - Trang 1069-1074 - 1998
Inhibition of intermediate-conductance Ca2+-activated K+ channel and cytoprotective properties of 4-piperidinomethyl-2-isopropyl-5-methylphenol Abstract
The ionic mechanisms and cytoprotective activities of 4-piperidinomethyl-2-isopropyl-5-methylphenol (THPI), an analogue of thymol, were investigated in HL-60 granulocytes and in human erythrocytes, respectively. THPI inhibited K+ outward current (IK) in a concentration-dependent manner in HL-60 leukocytes, with an IC50 value of 4 μM. Neither iberiotoxin (200 nM) nor paxilline (1 μM) suppressed the amplitude of IK, whereas clotrimazole (5 μM) significantly inhibited it. In the inside-out configuration of single channel recordings, application of THPI (5 μM) into the bath medium did not alter the single-channel conductance of intermediate-conductance Ca2+-activated K+ (IKCa) channels (i.e KCa3.1 channels), but it suppressed the channel activity significantly. THPI-induced inhibition of IKCa channels was reversed by a further application of 1-ethyl-2-benzimidazolinone (10μM). THPI-induced reduction in IKCa-channel activity in these cells was primarily due to a decrease in mean open time. These results provide direct evidence that THPI is capable of suppressing the activity of IKCa channels in HL-60 cells. The antioxidant action of THPI also revealed a beneficial cytoprotective effect against mitomycin C-mediated haemolytic effect in human erythrocytes. The results of this study suggest that blockade of IKCa channels and the membrane-protecting activity of THPI would combine to have beneficial effects in lessening the severity of haemolytic crisis and reducing anaemia in sickle cell disease.
Journal of Pharmacy and Pharmacology - Tập 59 Số 5 - Trang 679-685 - 2007
Statins and osteoporosis: new role for old drugs Abstract
Osteoporosis is the most common bone disease, affecting millions of people worldwide and leading to significant morbidity and high expenditure. Most of the current therapies available for its treatment are limited to the prevention or slowing down of bone loss rather than enhancing bone formation. Recent discovery of statins (HMG-CoA reductase inhibitors) as bone anabolic agents has spurred a great deal of interest among both basic and clinical bone researchers. In-vitro and some animal studies suggest that statins increase the bone mass by enhancing bone morphogenetic protein-2 (BMP-2)-mediated osteoblast expression. Although a limited number of case—control studies suggest that statins may have the potential to reduce the risk of fractures by increasing bone formation, other studies have failed to show a benefit in fracture reduction. Randomized, controlled clinical trials are needed to resolve this conflict. One possible reason for the discrepancy in the results of preclinical, as well as clinical, studies is the liver-specific nature of statins. Considering their high liver specificity and low oral bioavailability, distribution of statins to the bone microenvironment in optimum concentration is questionable. To unravel their exact mechanism and confirm beneficial action on bone, statins should reach the bone microenvironment in optimum concentration. Dose optimization and use of novel controlled drug delivery systems may help in increasing the bioavailability and distribution of statins to the bone microenvironment. Discovery of bone-specific statins or their bone-targeted delivery offers great potential in the treatment of osteoporosis. In this review, we have summarized various preclinical and clinical studies of statins and their action on bone. We have also discussed the possible mechanism of action of statins on bone. Finally, the role of drug delivery systems in confirming and assessing the actual potential of statins as anti-osteoporotic agents is highlighted.
Journal of Pharmacy and Pharmacology - Tập 58 Số 1 - Trang 3-18 - 2006
Ion-pair Formation as a Strategy to Enhance Topical Delivery of Salicylic Acid Abstract
An in-vitro study was carried out to determine the possibility of improving the efficiency of transdermal delivery of salicylate through human epidermis by ion-pair formers (alkylamines and quaternary ammonium ions). Further, the relationship between the physico-chemical properties of the counter-ions and salicylate flux was examined.
It was found that flux can be related to the conductivity associated with the penetrant solution, molecular size of the counter-ion and lipophilicity expressed as either octanol/water partition coefficient of the ion pairs or the carbon chain-length of the counter-ions.
Equations have been developed to predict salicylate flux from these physicochemical parameters.
Journal of Pharmacy and Pharmacology - Tập 52 Số 8 - Trang 919-928 - 2000
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