Martin A. Wahl

Bio: Martin A. Wahl is an academic researcher from University of Tübingen. The author has contributed to research in topics: Pancreatic islets & Insulin. The author has an hindex of 16, co-authored 43 publications receiving 2528 citations.

Pharmacology of Curcuma longa

Abstract: The data reviewed indicate that extracts of Curcuma longa exhibit anti-inflammatory activity after parenteral application in standard animal models used for testing anti-inflammatory activity It turned out that curcumin and the volatile oil are at least in part responsible for this action It appears that when given orally, curcumin is far less active than after ip administration This may be due to poor absorption, as discussed Data on histamine-induced ulcers are controversial, and studies on the secretory activity (HCl, pepsinogen) are still lacking In vitro, curcumin exhibited antispasmodic activity Since there was a protective effect of extracts of Curcuma longa on the liver and a stimulation of bile secretion in animals, Curcuma longa has been advocated for use in liver disorders Evidence for an effect on liver disease in humans is not yet available From the facts that after oral application only traces of curcumin were found in the blood and that, on the other hand, most of the curcumin is excreted via the faeces it may be concluded that curcumin is absorbed poorly by the gastrointestinal tract and/or underlies presystemic transformation Systemic effects therefore seem to be questionable after oral application except that they occur at very low concentrations of curcumin This does not exclude a local action in the gastrointestinal tract

Micronization of pharmaceutical substances by the Rapid Expansion of Supercritical Solutions (RESS): a promising method to improve bioavailability of poorly soluble pharmaceutical agents

Abstract: A multitude of pharmaceutical substances are often insoluble or only slightly soluble in aqueous media and the application of oral or injectable drugs is often limited by its low bioavailability. A promising method to improve the bioavailability of pharmaceutical agents is the Rapid Expansion of Supercritical Solutions (RESS). The RESS-process enables the micronization of thermally labile materials and the formation of particles of less than 500 nm in diameter. Our current research is aimed towards an improved understanding of the relationship between process parameters and particle characteristics and to explore new areas of application for nanoscale particles. Therefore, experimental investigations and numerical simulations were performed. Measurements were carried out for Benzoic acid, the pharmaceuticals Griseofulvin and -Sitosterol with the solvents CO2 (Carbon dioxide) and CHF3 (Trifluoromethane). These experiments led to particle sizes in the range of 200–500 nm depending on solvent and pre and postexpansion conditions. RESS-modelling is focused on the flow through the nozzle, the supersonic freejet, the Mach shock and particle growth in the expansion unit. From these calculations follows that particles are formed as small as 2–8 nm in the supersonic freejet. Hence, the conditions inside the expansion chamber are one key factor to control particle size. Furthermore, experiments show that the RESS processing of Griseofulvin leads to a significantly better dissolution rate of the drug resulting in an improved bioavailability. Moreover, stable suspensions of nanoscale particles of -Sitosterol were produced by the rapid expansion of a supercritical mixture through a capillary nozzle into aqueous solutions. The particle sizes of -Sitosterol in the aqueous solution were smaller or equal to those produced by RESS into air without the surfactant solution. © 2002 Elsevier Science B.V. All rights reserved.

Comparative evaluation of ibuprofen/β-cyclodextrin complexes obtained by supercritical carbon dioxide and other conventional methods

Abstract: Purpose The preparation of drug/cyclodextrin complexes is a suitable method to improve the dissolution of poor soluble drugs. The efficacy of the Controlled Particle Deposition (CPD) as a new developed method to prepare these complexes in a single stage process using supercritical carbon dioxide is therefore compared with other conventional methods.

Simultaneous Formation and Micronization of Pharmaceutical Cocrystals by Rapid Expansion of Supercritical Solutions (RESS)

Abstract: Purpose We investigated the RESS process as a means of simultaneous micronization and cocrystallization of a model drug with poor aqueous solubility.

Complex formation of Ibuprofen and β-Cyclodextrin by controlled particle deposition (CPD) using SC-CO2

Abstract: Modern therapeutically used drugs are often lipophilic compounds To reach the target structures, the drugs must be dissolved in physiological fluids and absorbed through entrance ports In modern medicine, due to costs, convenience and compliance, oral application of solid forms is the preferential way Since the bioavailability of orally applied drugs depends on the velocity of dissolution and absorption, methods to increase the dissolution of the lipophilic substances are often necessary to obtain significant blood levels A well suitable way is the reduction of particle size to increase the dissolution velocity However submicron particles are very difficult to be included in solid dosage forms To overcome this, the controlled particle deposition (CPD) process was developed The key idea behind CPD is to dissolve the drug of interest in supercritical CO 2 , followed by permeation of the supercritical solution into the pores of the carrier and precipitation of the drug inside the pores Thus, the attractive feature of CPD is the possibility to produce solvent-free, drug loaded carrier particles in a single processing step In order to ensure that both, the drug and the carrier, exist as a solid under the conditions of study, the phase behaviour of RS (±)-Ibuprofen and of β-Cyclodextrin in the presence of CO 2 was investigated prior to the inclusion experiments The results of the present investigations show, that an almost complete inclusion of RS (±)-Ibuprofen in β-Cyclodextrin at the solid state could be achieved In addition, the dissolution rate of the complex formed by CPD was found to be significantly higher than that of untreated RS (±)-Ibuprofen and its physical mixture with β-Cyclodextrin

Curcumin: From ancient medicine to current clinical trials

Abstract: Curcumin is the active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa). Curcumin has a surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. The pleiotropic activities of curcumin derive from its complex chemistry as well as its ability to influence multiple signaling pathways, including survival pathways such as those regulated by NF-κB, Akt, and growth factors; cytoprotective pathways dependent on Nrf2; and metastatic and angiogenic pathways. Curcumin is a free radical scavenger and hydrogen donor, and exhibits both pro- and antioxidant activity. It also binds metals, particularly iron and copper, and can function as an iron chelator. Curcumin is remarkably non-toxic and exhibits limited bioavailability. Curcumin exhibits great promise as a therapeutic agent, and is currently in human clinical trials for a variety of conditions, including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer, psoriasis and Alzheimer’s disease.

Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation.

Abstract: A wide array of phenolic substances, particularly those present in edible and medicinal plants, have been reported to possess substantial anticarcinogenic and antimutagenic activities. The majority of naturally occurring phenolics retain antioxidative and anti-inflammatory properties which appear to contribute to their chemopreventive or chemoprotective activity. Cyclooxygenase-2 (COX-2) inducible and nitric oxide synthase (iNOS) are important enzymes that mediate inflammatory processes. Improper up-regulation of COX-2 and/or iNOS has been associated with pathophysiology of certain types of human cancers as well as inflammatory disorders. Since inflammation is closely linked to tumor promotion, substances with potent anti-inflammatory activities are anticipated to exert chemopreventive effects on carcinogenesis, particularly in the promotion stage. Examples are curcumin, a yellow pigment of turmeric (Curcuma longa L., Zingiberaceae), the green tea polyphenol epigallocatechin gallate (EGCG), and resveratrol from grapes (Vitis vinifera, Vitaceae) that strongly suppress tumor promotion. Recent studies have demonstrated that eukaryotic transcription factor nuclear factor-kappa B (NF-kappa B) is involved in regulation of COX-2 and iNOS expression. Several chemopreventive phytochemicals have been shown to inhibit COX-2 and iNOS expression by blocking improper NF-kappa B activation. Multiple lines of compelling evidence indicate that extracellular-regulated protein kinase and p38 mitogen-activated protein kinase are key elements of the intracellular signaling cascades responsible for NF-kappa B activation in response to a wide array of external stimuli. Curcumin, EGCG and resveratrol have been shown to suppress activation of NF-kappa B. One of the plausible mechanisms underlying inhibition of NF-kappa B activation by aforementioned phytochemicals involves repression of degradation of the inhibitory unit I kappa B alpha, which hampers subsequent nuclear translocation of the functionally active subunit of NF-kappa B.