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Biomedical subjects

C G Wilson

Publications and source records attributed to C G Wilson.

At least 91 records · Page 5Linked to original sources

Intranasal drug delivery by spray and drops.

A solution of 99mTc-labelled human serum albumin was administered into the nose as a spray and as one or three drops. The patterns of deposition and the rates of clearance in normal subjects were monitored by gamma scintigraphy. The spray was deposited mainly in the atrium, and cleared slowly into the pharynx. The single drop spread more extensively than the spray, while the three drops were sufficient to cover most of the walls of the nasal cavity. Clearance was faster following administration of the drops. These factors have implications when designing dosage regimens for drugs administered by the intranasal route.

Administration, Intranasal↗

Recent advances in the use of microspheres for targeted therapy.

In recent years the concept of using small colloidal particles for the selective delivery of drugs has been explored experimentally using a variety of different physical systems (for example, phospholipid vesicles (liposomes), triglyceride emulsions, albumin microspheres) and routes of administration. In such studies the aim has been to target a potent pharmacological agent on an organ or tissue site, thereby reducing adverse reactions and side-effects, or to provide a means of controlled release. The design of appropriate delivery systems must take into account the nature of the target and physiological barriers to targeting as well as factors such as drug loading and drug release, stability of the carrier system and its biocompatibility and biodegradation. Targeting with microspheres can be divided into passive methods that rely upon physiological and physicochemical determinants such as entrapment in capillary beds (lungs - particle size) or uptake by phagocytic cells (liver-surface characteristics), an active method whereby the particle is directed to a specific site through the use of surface coatings (surfactants, glycolipids, monoclonal antibodies) or a material sensitive to an external influence. Candidate systems presently under study are described. These include lipid emulsions for intravenous administration and microspheres for intra-articular delivery.

Adrenal Cortex Hormones↗

Effect on finger tremor of withdrawal of long-term treatment with propranolol or atenolol.

The effect of the withdrawal of long-term beta-adrenoceptor blockade on pulse rate and finger tremor was studied in 27 patients who had been treated for 2 years following an uncomplicated myocardial infarction with either atenolol, propranolol or placebo. During treatment, pulse rate was significantly lower in patients treated with propranolol or atenolol compared with placebo. Compared with the response in the placebo group the mean increase in tremor on withdrawal of propranolol was statistically significant for postural and for work tremor in both hands. A significant increase in tremor on withdrawal of atenolol occurred only in the postural position and in a narrow frequency band (left hand, 7-11 Hz; right hand, 7-9 Hz). The differences in the effect on tremor of withdrawal of treatment with propranolol or atenolol in doses which produced similar reductions in heart rate, emphasise the beta 2 classification of peripheral receptors associated with normal muscle tremor but do not exclude the involvement of beta 1-adrenoceptors.

Atenolol↗

Preparation and evaluation of biodegradable polymeric systems for the intra-articular delivery of drugs.

Colloidal suspensions of four biodegradable polymers, polylactic acid (PLA), polybutylcyanoacrylate (PBCA), gelatin (PG) and albumin (PA) were prepared within the size range 1-10 micron. In-vivo biocompatibility tests with synovial tissues were carried out to assess the irritancy of the polymers following intra-articular injection into rabbit knee joints. PLA, PBCA and PG were found to cause joint inflammation whereas PA was well tolerated by the tissues. PA microspheres may provide a means of sustaining the release and reducing the rate of clearance of drugs from the knee joint.

Albumins↗

The in-vivo evaluation of an osmotic device (Osmet) using gamma scintigraphy.

The release of a radiolabelled marker from an orally administered osmotic pump device (Osmet) has been evaluated in-vivo in a group of 6 subjects, using the technique of gamma scintigraphy. The duration of residence of the pump in the stomach was greatly influenced by food intake. However, the release of the marker from the device was independent of food and position within the gastrointestinal tract. Furthermore, the material released from the osmotic pump was well distributed in the gastrointestinal tract. Good agreement between in-vitro and in-vivo release rates was obtained.

Adult↗

The effect of different oils on the absorption of probucol in the rat.

The effect of oily vehicles on the gastrointestinal absorption of the hypocholesterolaemic agent probucol has been investigated in the rat. The plasma concentration was determined following its administration in arachis oil (peanut oil), Miglyol 812 (fractionated coconut oil) and liquid paraffin. The total absorption of the drug, calculated as the area under the plasma concentration time curve, was significantly greater for the arachis oil formulation than with the other vehicles. The drug was selectively absorbed via the lymphatic system, lymph drug concentrations being highest following co-administration of arachis oil.

Animals↗

Precorneal drainage of polyvinyl alcohol solutions in the rabbit assessed by gamma scintigraphy.

A method for monitoring the ocular distribution of solutions for ophthalmic use was developed using the technique of gamma scintigraphy. This method was used to monitor the effects of polyvinyl alcohol on the precorneal drainage of [99mTc]pertechnetate in the rabbit. The rate of drainage of solutions decreased on addition of PVA and precorneal residence of the marker was significantly prolonged, compared with saline controls, at a PVA concentration of 5% W/V. Increases in the activity in the inner canthal region mirrored the decrease in corneal counts. The method has a more general application for the study of ophthalmic formulations and devices in larger mammals and in man.

Animals↗

The regeneration of rectal epithelium in the rat following wounding with suppositories of polyoxyethylene (23) lauryl ether.

The regeneration of the epithelial compartments of the rectal mucosa in rats has been quantified at time intervals up to one week following wounding with suppositories of the surfactant polyoxyethylene-(23)-lauryl ether. Regeneration of glandular tissue was complete within one week of the wounding, with new glands arising from residual gland bases and from surface invagination of empty crypt skeletons and underlying granulation tissue. This method of wounding appears to be particularly useful for the study of epithelial regeneration since there was a minimal connective tissue response to the insult.

Animals↗

Lead sulphide and traditional preparations: routes for ingestion, and solubility and reactions in gastric fluid.

Lead sulphide frequently occurs as a fallacious materia medica in traditional preparations used throughout the Moslem world. Although one of the least soluble lead compounds, use of this material as an eye powder has been directly associated with elevated blood-lead levels in children. Data are presented from animal studies which show the primary route for ingestion of the eye cosmetic is not transcorneal transport. Conversion of the sulphide to the more soluble (and hence more readily absorbed) chloride form is shown to occur in gastric fluid and, significantly, a marked dependence of the rate of dissolution on particle size is found. This may explain the disparity in previous reported values for the extent of absorption of ingested lead sulphide.

Animals↗

The effect of oils on the lymphatic absorption of DDT.

Plasma concentrations of DDT were measured in conscious rats following oral administration in arachis oil, Miglyol 812 (fractionated coconut oil), liquid paraffin or as a fine suspension in water. The total absorption of DDT, calculated as the area under the plasma concentration time curve, was significantly greater for the arachis oil formulation compared to the other vehicles. In anaesthetized rats it was shown that DDT absorption was almost totally via the lymphatic system, and that lymph levels of DDT were highest following administration in arachis oil. Measurement of lymph flow showed that this enhanced absorption of DDT in the presence of arachis oil was not due to an increased flow as both arachis oil and liquid paraffin stimulated lymph production to the same extent.

Absorption↗

Altered ocular absorption and disposition of sodium cromoglycate upon ion-pair and complex coacervate formation with dodecylbenzyldimethylammonium chloride.

Ion-pair formation between the dianionic drug sodium cromoglycate and dodecylbenzyldimethylammonium chloride has been found to alter the extent and rate of corneal penetration of both large ions upon their coadministration. Additionally, using a complex coacervate of the two large ions as the applied dose form (in which the complex is in equilibrium with the ion pairs), a change in the overall disposition of both large ions to the various components of the eye is observed.

Absorption↗

Finger tremor and cigarette smoking.

1 Finger tremor was recorded with a strain gauge and an accelerometer. 2 Records were subjected to frequency analysis and the amplitude or power at frequencies up to 25 Hz were computed. 3 Comparison was made between the tremor during a control period, during sham smoking and during smoking a cigarette. 4 Smoking significantly increases tremor amplitude by at least twofold over all frequencies from 1 Hz to 25 Hz.

Adolescent↗

The distribution and fate of 131I-labelled liposomes.

The distribution of 131I-labelled liposomes with sodium iodide entrapped in the aqueous core has been compared with that of a preparation containing iodinated phospholipid, following i.v. administration to rabbits. Liver uptake was observed initially with both liposomes, but the distribution of the former preparation soon became indistinguishable from that of [131I] sodium iodide. Iodine-131 was still detectable in the liver 150 h after administration of the phospholipid labelled material. Scintigrams showing the distributions of the radionuclides following administration of 131I-labelled liposomes and 99mTc-DTPA liposomes indicate that there may be some biliary clearance.

Animals↗

Inhibition of thiabendazole metabolism in the rat.

1. A single oral dose of desmethylimipramine (80 mg/kg) administered to rats inhibited the hepatic microsomal hydroxylation of thiabendazole (45%), aniline (30%), biphenyl (30%) and ethylmorphine (15%) in vitro at 5 h after dosage; there was no decrease in cytochrome P-450 or b5. 2. A single oral dose of ethoxyquin (200 mg/kg) to rats inhibited the hepatic microsomal hydroxylation of thiabendazole (65%), aniline (40%) and biphenyl (40%) in vitro at 1 h after dosage; inhibition was less at 5 h. There were no changes in the contents of cytochromes P-450 and b5. 3. The max. plasma concn. of thiabendazole occurred 2--4 h after oral dosing (50--200 mg/kg) to rats. Thiabendazole (100 mg/kg) administered orally 30 min after oral ethoxyquin (400 mg/kg) or thiabendazole (200 mg/kg) administered orally 30 min after oral desmethylimipramine (80 mg/kg) delayed absorption of the thiabendazole and resulted in markedly markedly decreased plasma concentration of the anthelmintic. 4. Simultaneous administration of ethoxyquin (300 mg/kg) potentiated the anthelmintic effect of thiabendazole (750 mg/kg) on the helminth parasite, Nematospiroides dubius, in the mouse. Desmethylimipramine showed no similar potentiation.

Animals↗