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Biomedical subjects

S S Davis

Publications and source records attributed to S S Davis.

At least 199 records · Page 11Linked to original sources

Lymphoid tissue responses to a novel perfluorochemical emulsion in rats.

The effects of a novel perfluorochemical emulsion on rat lymphoid tissues and antibody production against sheep red blood cells (SRBC) have been studied. The responses were compared with those following injection of identical doses of the proprietary emulsion, Fluosol-DA 20% (F-DA). Liver weight was increased up to 15% at 8 days following intravenous (i.v.) or intraperitoneal (i.p.) injection of the novel emulsion but was unaffected by F-DA injection. Spleen weight also increased by a maximum of 20% in response to i.p. injection of the novel emulsion but this was less than increases of up to 44% which occurred in F-DA-injected rats. Thymus weight decreased (P less than 0.05) following i.p. injection of the novel emulsion whereas mesenteric lymph node (MLN) weight remained unchanged. However, MLN weight was increased in response to i.v. injected F-DA, while thymus weight showed a small increase following i.p. F-DA injection. Mean plasma antibody titres to SRBC were significantly (P less than 0.01) increased at 7 days after immunization in rats pretreated with i.p. injections of either the novel emulsion or F-DA; titres in animals pretreated with i.v. injections of either emulsion were similar to control.

Animals↗

The effect of molecular size on the nasal absorption of water-soluble compounds in the albino rat.

The nasal absorption of a range of water-soluble compounds with different molecular weights, 4-oxo-4H-1-benzopyran-2-carboxylic acid (mol. wt 190), p-aminohippuric acid (mol. wt 194), inulin (mol. wt 5200) and dextran (mol. wt 70,000), has been investigated in the male Wistar rat. Compounds were instilled into the nasal cavities of anaesthetized animals, and for comparison, similar doses were administered intravenously. Serial samples of bile and urine were collected for up to 6 h. Nasal absorption, estimated by comparison of the extent of excretion in bile and urine following intranasal and intravenous administration, was 100% for 4-oxo-4H-1-benzopyran-2-carboxylic acid (1 mg kg-1), 75% for p-aminohippuric acid (1 mg kg-1), 15% for inulin (0.1 mg kg-1) and 2.8% for dextran (0.25 mg kg-1). The log molecular weight gave a good linear correlation with the log per cent intranasally absorbed (correlation coefficient of -0.996). From the molecular weight relationship, these data infer aqueous channel mechanisms for the nasal absorption of water-soluble compounds.

Absorption↗

Albumin microspheres for intra-articular drug delivery: investigation of their retention in normal and arthritic knee joints of rabbits.

The retention of 131I-labelled albumin microspheres and microsphere-entrapped [131I]rose bengal was investigated in normal and experimentally arthritic knee joints of rabbits. Albumin microspheres were cleared slowly from the joint cavity and no significant difference was observed between normal and inflamed joints. Entrapment of rose bengal within albumin microspheres was found to delay the clearance of the drug from the joint when compared with a solution of rose bengal. In addition, the retention time for entrapped rose bengal was dependent on the degree of inflammation present.

Albumins↗

The effect of polycarbophil on the gastric emptying of pellets.

The influence of the putative bioadhesive, polycarbophil, on the gastric emptying of a pellet formulation, has been investigated in three fasted subjects. The pellets were radiolabelled with technetium-99m. Gastric emptying was measured using the technique of gamma scintigraphy. The pellets emptied from the stomach rapidly and in an exponential manner. Polycarbophil did not retard the gastric emptying of the pellets.

Acrylic Resins↗

Lipid vehicles for intestinal lymphatic drug absorption.

The lipoprotein fractions in mesenteric lymph were monitored following intraduodenal administration of arachis oil and oleic, linoleic and linolenic fatty acids to rats. An increase in the chylomicron fraction, but not the VLDL or LDL fraction, was observed with each lipid. The greater the degree of unsaturation of the fatty acid, the more rapid the onset of chylomicron synthesis. The administration of linoleic acid and arachis oil produced the highest concentration of chylomicrons in the lymph. These results reflect differences in the rate of absorption and biochemical metabolism of the lipids and have implications for the selection of vehicles for the delivery of drugs by the lymphatic route.

Animals↗

Nanoparticles in drug delivery.

Alkylcyanoacrylates can be polymerized in acidified aqueous media by a process of anionic polymerization. The small particles produced tend to be monodisperse and have sizes in the range of 20 to 3000 nm depending upon the polymerization conditions and the presence of additives in the form of surfactants and other stabilizers. The polyalkylcyanoacrylate nanoparticles so produced have been studied in recent years as a possible means of targeting drugs to specific sites in the body, with particular emphasis in cancer chemotherapy. The small colloidal carriers are biodegradable and drug substances can be incorporated normally by a process of surface adsorption. The review by Davis and others considers the formulation of nanoparticles, the important physicochemical variables such as pH, monomer concentration, added stabilizers, ionic strengths, etc., as well as the characteristics of the particle so created in terms of surface charge, particle size, and molecular weight. Monodisperse particles in the range of 20 to 3000 nm can be obtained. In addition, by the use of stabilizers such as dextran and its derivatives, which can be incorporated into the nanoparticle surface by a process of polymer grafting, it is possible to make nanoparticles with interesting surface characteristics and different surface charges (sign). The stability of nanoparticles in vitro and their biodegradation in vivo are examined, and the possible formation of toxic products such as formaldehyde is highlighted. Alternative biodegradable acrylates are mentioned. Drugs can be incorporated into nanoparticles by either direct incorporation during the polymerization process or adsorption to preformed nanoparticles. The efficiency of the incorporation and the release characteristics of model compounds as well as anticancer drugs are discussed. Methods for examining these processes, including the determination of adsorption and desorption, kinetics, and isotherms, are mentioned. Selectivity in drug targeting can, in theory, be achieved by the attachment of some form of homing device, normally a monoclonal antibody or a lectin. Work in vitro and in vivo, where nanoparticles have been coated with monoclonal antibodies, is described. Finally, methods for the labeling of nanoparticles with gamma-emitting radionuclides are presented, and results obtained in animal species are given.

Antibodies, Monoclonal↗

Effect of a selected suppression of the reticuloendothelial system on the distribution of model carrier particles.

The distribution of small labeled latex test particles has been studied after intravenous administration to the rabbit using the noninvasive technique of gamma scintigraphy. The reticuloendothelial system was suppressed using polystyrene latex particles and dextran sulfate as blocking agents. Both materials gave rise to significant uptake of particles in the lungs of the order of 60% of the administered dose. The effect seen with suppression with latex particles remained unaltered over an 8-d period, while for suppression with dextran sulfate the effect was transient, and particles that were initially deposited in the lungs were subsequently redistributed to the liver. The results are discussed in terms of previous studies on reticuloendothelial suppression using different agents, test colloids, and animal models.

Animals↗

In vitro and clinical studies on intravenous feeding mixtures comprising fat emulsion, amino acid and electrolytes.

This paper describes the effect of the amino acid mixture Freamine II on the physical stability of Intralipid fat emulsion. The amino acid-fat emulsion mixture was also administered to patients requiring intravenous nutrition and its clinical and biochemical effects were assessed. The amino acid-fat emulsion mixture was stable on storage for 48 hours as judged by flocculation and particle growth measurements made in the presence of 20 mmol/1 monovalent cations at 2 mmol/1 diavalent cations. Long-term storage of mixtures containing Freamine II is not recommended because of an interaction between the emulsifier and the amino acids. In a small open trial patients maintained their serum albumin concentrations. There was no evidence of impaired pulmonary function even in those subjects with impaired fat clearance.

Journal Article↗

Studies on fat emulsions in combined nutrition solutions.

The effect of added Aminoplex, Glucoplex, nutrient additives and calcium chloride on the stability of a fat emulsion (Intralipid) has been examined. The conclusions are as follows: Aminoplex and Glucoplex do not cause a decrease in the physical stability of mixed systems that contain fat droplets stored at room temperature for at least 7 days. The mixed systems are stable even in the presence of high electrolyte loads (greater than 600 mmol litre-1 expressed in terms of monovalent cation). The amino acids in Aminoplex could be having a stabilizing effect on the emulsion system by the adsorption of components to the oil/water interface.

Drug Stability↗

Transit of pharmaceutical dosage forms through the small intestine.

The gastrointestinal transit of pharmaceutical dosage forms has been measured in 201 studies in normal subjects using gamma scintigraphy. Solutions, small pellets, and single units (matrix tablets and osmotic pumps) were administered with different amounts of food in the stomach, ranging from fasted state to heavy breakfast. Gastric emptying was affected by the nature of the dosage form and the presence of food in the stomach. Solutions and pellets were emptied even when the stomach was in the digestive mode, while single units were retained for long periods of time, depending on the size of the meal. In contrast, measured intestinal transit times were independent of the dosage form and fed state. The small intestinal transit time of about three hours (mean +/- 1 h SEM) has implications for the design of dosage forms for the sustained release of drugs in specific positions in the gastrointestinal tract.

Adult↗

Peripheral nerve conduction studies and bulbocavernosus reflex in the investigation of impotence.

Patients with erectile dysfunction underwent sensory and motor conduction and bulbocavernosus reflex tests to determine the incidence of peripheral nerve involvement. Of a total of 111 patients, abnormal sensory conduction was found in 87 (78%), abnormal motor conduction in 56 (50%), and abnormal bulbocavernosus reflex in 40 (36%). Most of these patients had other medical problems. Objective evidence of peripheral nerve involvement helped in the management of these patients.

Adult↗

The nasal absorption of sodium cromoglycate in the albino rat.

The intranasal absorption of sodium cromoglycate has been investigated in the adult male COBS/Wistar rat. Sodium cromoglycate (1 mg kg-1) was instilled into the nasal cavities and for comparison animals were also similarly dosed intravenously or sub-lingually. Serial samples of blood or bile were collected. After intravenous administration, the area under the plasma concentration curve (AUC0-infinity) was 32 micrograms min ml-1 corresponding to a plasma clearance of 13 ml min-1 and an elimination rate constant of 0.049 min-1. Plasma concentrations of radioactivity after intranasal administration rose to a mean peak of 0.3 micrograms ml-1 approximately 20 min after dosing and fell to 0.03 micrograms min ml-1 at 3 h. The AUC0-3 was 19 micrograms min ml-1 corresponding to an absorption of 60% over 3 h. The absorption rate constant (ka) was 0.059 min-1. The total amount of sodium cromoglycate excreted in bile after intravenous administration was 56%. The amount of compound excreted in the bile was 30% after intranasal administration corresponding to an absorption of 53%. Plasma and bile data therefore show good agreement. Total excretion in the bile over 3 h after sub-lingual administration was 3%, demonstrating that this route made no significant contribution to the intranasal results. The absorption of sodium cromoglycate is independent of variations in the technique including changes in the orientation of the rat or blocking of the nasopalatine. The techniques used minimized other competing nasal clearance processes such as mucociliary clearance.

Absorption↗

The use of gamma scintigraphy to follow the gastrointestinal transit of pharmaceutical formulations.

The technique of gamma scintigraphy has been used to follow the transit of a solution and a pellet formulation in the gastrointestinal tract of healthy volunteers. The emptying of the formulations from the stomach and their arrival at the caecum could be quantified, thereby allowing calculation of transit times for the small intestine. Gastric emptying was affected by the nature of the formulation, i.e. liquid or solid. However, transit through the small intestine was independent of the nature of the administered material.

Adult↗

Use of adjuvants for enhancement of rectal absorption of cefoxitin in humans.

The biological availability of cefoxitin administered rectally in the form of suppositories was examined in six human subjects by a cross-over design. Four different suppository systems containing adjuvants expected to enhance the absorption of the drug were studied. The presence of sodium salicylate and a nonionic surface-active agent, Brij 35, gave increased bioavailability as high as 20% compared with 3% for a system without adjuvants. The quantity of sodium salicylate was found to have an influence on the quantity of cefoxitin absorbed, and the salicylate was absorbed over an extended period of time from the rectum. The suppositories were well tolerated, and there were no adverse effects on bowel flora.

Biological Availability↗