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Biomedical subjects

S S Davis

Publications and source records attributed to S S Davis.

At least 217 records · Page 12Linked to original sources

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↗

Evaluation of impotence in older men.

Careful evaluation was carried out in 93 men older than 50 with erectile dysfunction. Their mean age was 61 years and the disorder had been present for a mean of 4.5 years. While 14 men (15%) had psychosocial factors that may have been pertinent, only 2 scored poorly on an Affect Balance Scale and 3 were receiving psychoactive medications. Results of nocturnal penile tumescence were abnormal in 91%. In 39% penile-brachial pressure indices were suggestive of pelvic vascular disease and in 9% were consistent with a pelvic "steal syndrome." Pelvic or peripheral nerve conduction disorders were also commonly seen in 54%. Endocrinopathy may have contributed to the dysfunction in 35%. Twenty-one men had diabetes mellitus, two new cases of hypothyroidism were discovered and hypogonadism was diagnosed definitely in four and considered likely in five others. Coexisting medical conditions were found in more than 90% of the men, especially hypertension, use of antihypertensive medications and atherosclerotic disease. Previous prostatectomies (19%) and vasectomies (30%) were common in the surgical histories. Given the wide range of disorders uncovered in older men complaining of impotence, diagnostic study of potential causes may lead to a more rational approach for the evaluation and management of these men.

Aged↗

A new mucotropic agent--in vitro and in vivo evaluation of 2-alpha-thenoylthiopropionylglycine (bronchoplus).

A new mucotropic agent, 2-alpha-thenoylthiopropionylglycine (TTPG) has been evaluated using two in vitro mucus models (pig gastric mucin and human bronchial mucus) and an in vivo model, the oral administration for a period of 7 days to a mini-pig fitted with a tracheal-pouch. TTPG at 2% concentration caused a 40% reduction in the viscosity of mucus gels in vitro, as compared to a control with water. Tracheal mucus samples collected from the pouch were examined rheologically and biochemically. The amount of glycoprotein secreted increased after administration of TTPG (440 to 616 micrograms/mg dry weight). The glycoproteins also appeared to be more acidic after TTPG. An increase in the sulphydryl concentration of the mucus was observed, suggesting that a hydrolysis product of TTPG had crossed the blood-mucus barrier. An increase in the viscosity and elasticity of the mucus gel occurred during the treatment period.

Acetylcysteine↗

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↗

Tissue distribution of poly(hexyl 2-cyanoacrylate) nanoparticles coated with monoclonal antibodies in mice bearing human tumor xenografts.

The tissue distribution of naked and either normal immunoglobulin G or monoclonal antibody (antitumor osteogenic sarcoma)-coated poly(hexyl-2-cyanoacrylate) nanoparticles was studied in mice bearing human tumor xenografts to evaluate the applicability of the systems for tumor targeting. All systems were shown to deposit mainly in the liver and spleen and no significant uptake was found in the tumors for either the naked or antibody-coated nanoparticles.

Adsorption↗

Thermodynamics of distribution of p-substituted phenols between aqueous solution and organic solvents and phospholipid vesicles.

The distribution of p-substituted phenols between 0.15 M NaCl and a range of organic solvents (including 1-octanol) was examined over a range of temperatures. The thermodynamic parameters of transfer, delta G, delta H, and delta S, were determined and the values examined in the light of Hildebrand and Scott's solubility parameter theory, and the collision complexes between solute and organic solvent. Delta H of transfer was positive for nonpolar solvents and negative for 1-octanol; the transfer processes were entropy and enthalpy dominated, respectively. The distribution of the phenols into phospholipid vesicles was examined below the phase-transition temperature. Although delta G of transfer for vesicle-water systems was similar to that for octanol-water systems, the full thermodynamic analysis indicated that the two systems were dissimilar. The use of vesicle distribution data in structure-activity studies is discussed.

Phenols↗

Effect of the nonionic surfactant poloxamer 338 on the fate and deposition of polystyrene microspheres following intravenous administration.

The blood clearance and organ deposition of polystyrene microspheres in the rabbit following intravenous injection has been investigated using the technique of gamma scintigraphy, blood and organ level measurements, and histology. Uncoated microspheres of 1.27-microns diameter were cleared rapidly from the blood and were taken up primarily by the reticuloendothelial system in the liver. Coating of the microspheres with the nonionic surface-active agent poloxamer 338 reduced the uptake in the liver and gave a corresponding increase in the lungs.

Animals↗

Periodontal surgery as an aid to restoring fractured teeth.

The periodontal, orthodontic, and prosthetic management of four indications for subgingival or subosseous tooth fractures has been discussed. The importance of having the aveolar crest a minimal distance of 2.5 mm from the margin of the restoration has been explained. The pitfalls of an external, rather than internal, bevel and flap procedure were assessed. Coordinated interspecialty therapy provides diverse, conservative treatment for the general practitioner and successful restorations for the patient.

Alveolectomy↗

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↗

Functional group contributions to the partitioning of phenols between liposomes and water.

The temperature dependency of the partitioning of p-alkylphenols and p-halophenols has been determined between dimyristoyl phosphatidylcholine liposomes and 0.15 M NaCl. Partition coefficients increased as a function of temperature below the endothermic phase transition temperature (Tc) of the phospholipid but decreased above this temperature. The transfer process was found to be entropy-dominated below and enthalpy-dominated above the Tc, although large negative entropy changes were observed. Regular changes in the thermodynamic functions, partition coefficients and functional group free energies occurred as a function of the alkyl chain length or size of the halogen substituent below but not above the Tc. This has tentatively been attributed to increased phenol-phospholipid interaction at the higher temperatures. The partitioning of p-fluorophenol behaved in a manner expected of fluorinated compounds, yielding relatively low partition coefficients, but it produced an additional effect of markedly lowering the Tc of dimyristoyl phosphatidylcholine. Good correlations of the partition coefficients in liposomes with those in bulk organic solvents and with molecular size of the solute have been obtained.

Dimyristoylphosphatidylcholine↗