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Biomedical subjects

S S Davis

Publications and source records attributed to S S Davis.

At least 127 records · Page 7Linked to original sources
PubMed1993

Effect of splenic congestion associated with haemolytic anaemia on filtration of 'spleen-homing' microspheres.

1. The surface of large model 125I-labelled polystyrene microspheres (220 nm in diameter) was coated with the polyoxyethylene/polyoxypropylene block co-polymer poloxamine-908. The coated microspheres were injected intravenously into rats. Up to 40% of the administered dose had accumulated in the spleen by a filtration mechanism, as compared with 5% for uncoated microspheres, at 3 h after administration. The enhanced splenic sequestration of microspheres was accompanied by a decrease in the liver uptake. In contrast, smaller poloxamine-908-coated microspheres (60 nm in diameter) effectively avoided uptake by both the liver and the spleen and remained in systemic circulation. 2. The effect of splenic congestion, associated with phenylhydrazine-induced haemolytic anaemia, on filtration of poloxamine-908-coated microspheres was studied. The enlarged spleen of the anaemic rats was incapable of efficiently filtering large poloxamine-908-coated microspheres when compared with the spleen of normal animals. This was suggested to be the result of extensive 'clogging' of the red pulp by damaged erythrocytes. However, the splenic filtration of large coated microspheres was still five-fold higher than that of uncoated microspheres of similar size in anaemic animals. 3. The potential use of large sterically stabilized colloids and drug carriers for selective spleen scanning and splenic drug delivery in pathological conditions, where anaemia prevails, is discussed. 4. Sterically stabilized microspheres may have potential for re-examining the microcirculatory pathways in healthy spleen and various splenomegalies.

Anemia, Hemolytic↗
PubMed1993

The pharmacokinetics and physiological effects of buprenorphine infusion in premature neonates.

1. The pharmacokinetics and physiological effects of buprenorphine were studied in 12 newborn premature neonates (27 to 32 weeks gestational age) who were given a loading dose of 3.0 micrograms kg-1 of buprenorphine followed by an intravenous infusion of 0.72 micrograms kg-1 h-1 of buprenorphine. Plasma concentrations of buprenorphine were measured during the infusion, at steady-state and for 24 h after the cessation of the buprenorphine infusion. 2. The mean steady-state plasma buprenorphine concentration (+/- s.d.) for an infusion rate of 0.72 micrograms kg-1 h-1 was 4.3 +/- 2.6 ng ml-1. 3. Buprenorphine clearance was 0.23 +/- 0.07 l h-1 kg-1, the elimination half-life was 20 +/- 8 h and the volume of distribution was 6.2 +/- 2.11 l kg-1. 4. Small but significant falls were noted in systolic blood pressure at 6 h and heart rate at 1, 6 and 12 h after the administration of buprenorphine, but these did not appear to cause any clinical deterioration. 5. Four of the 12 subjects studied required an increase in the infusion rate of buprenorphine to achieve adequate sedation. 6. The results suggest that this dosing regimen of buprenorphine is safe but may not be as effective as other opioids in producing sedation and analgesia in premature newborns.

Analgesics, Opioid↗
PubMed1993

Physicochemical properties of parenteral fat emulsions containing 20% triglyceride; Intralipid and Ivelip.

The paper describes an in-depth study of the parenteral fat emulsions, Intralipid 20% and Ivelip 20%. A large number of emulsion samples from separate containers and batches was sampled. The parameters measured were droplet size (both by photon correlation and laser diffraction), pH and zeta potential. These parameters were re-measured after the emulsions were subjected to a number of accelerated stability tests (freeze-thaw cycling, autoclaving and shaking). The results demonstrate that although the Intralipid is stable, it can show some variability between separate batches. The stability of Ivelip is high, and the variability between separate batches is extremely low.

Calcium↗
PubMed1993

Rheology of model aerosol suspensions.

The rheological properties of model aerosol suspensions at phase fractions of less than 5% w/v (phase ratio of 0.05) were investigated. The rheological profiles of lactose in chloroform, lactose in trichlorofluoromethane (Propellent 11, P11), and salbutamol sulphate in P11 have been investigated in the presence and absence of lecithin, a phospholipid surface-active agent. The relative viscosities of these disperse systems correlated with the increasing disperse phase fractions and the addition of surfactant was found to reduce these viscosities to a relative viscosity of approximately 1.0. The results suggest that the relative viscosity is a useful indicator of flocculation in these systems, and may be valuable in formulation development.

Aerosols↗
PubMed1993

Preparation of sub-100 nm human serum albumin nanospheres using a pH-coacervation method.

Human serum albumin (HSA) nanospheres of about 100 nm diameter were prepared using a pH-coacervation method whereby acetone was added to an HSA solution (pH 9.0). The particles obtained were cross-linked by glutaraldehyde. Increasing the pH of the HSA solution resulted in a gradual rise in the particle size of the resultant nanospheres. A higher cross-linking efficiency was obtained with increased glutaraldehyde concentration and cross-linking time. No significant differences in surface properties, as determined by zeta potential measurements, were recorded between particles prepared from HSA solutions with different pH. The nanospheres were quite stable over 4 days in both phosphate buffer saline (PBS) solution (pH 7.4) and rat serum, but degraded rapidly over 6 hours when incubated in PBS solution containing trypsin.

Animals↗
PubMed1992

The polyoxyethylene/polyoxypropylene block co-polymer poloxamer-407 selectively redirects intravenously injected microspheres to sinusoidal endothelial cells of rabbit bone marrow.

Small colloidal particulates (150 nm and below, in diameter) can be redirected specifically to the rabbit bone marrow following intravenous administration by coating their surface with the block co-polymer poloxamer-407, a non-ionic surfactant. The coated colloids are sequestered by the sinusoidal endothelial cells of the bone marrow and are accumulated in dense bodies within these cells. The uptake of poloxamer-407-coated colloids by marrow endothelial cells suggests that the steric repulsive barrier, imposed by the polyoxyethylene segment of the polymer, to particle-cell interaction can apparently be overcome by a specific interaction mechanism(s) with the cell surface. Such a dramatic uptake cannot be achieved with other block co-polymers of similar structure to poloxamer-407. The application of the current model for the site-specific targeting of drug carriers to bone marrow and the prevention of the adherence of metastases of tumours which selectively colonize the bone marrow endothelium is discussed.

Animals↗
PubMed1992

New developments in sustained-release antihypertensive therapy: formulation and pharmacokinetic considerations.

In order to achieve a consistently absorbed form of nifedipine over 24 hours, a novel formulation approach, INDAS, was used to develop a once-daily, sustained-release (SR) form of nifedipine that could provide effective control of blood pressure at a low total daily dose. The pharmacokinetic characteristics of this new formulation of nifedipine-SR were compared with those of divided doses of conventional nifedipine. The SR formulation was shown to achieve a lower peak plasma nifedipine level but with a prolonged plasma profile characterized by an extended time to peak plasma levels (Tmax), a higher trough plasma level, a longer apparent half-life, and a markedly lower peak-to-trough fluctuation in plasma nifedipine concentrations. In a separate study, the gastrointestinal transit parameters and physical characteristics of the SR tablet were evaluated. This study established that the large intestine is the major site of residence and absorption for this dosage form. The physical erosion and disintegration characteristics of the SR formulation are such that a well-maintained absorption of nifedipine is consistently achieved over the 24 hour dosing interval.

Adult↗
PubMed1992

Gamma scintigraphy in the evaluation of pharmaceutical dosage forms.

Gamma-scintigraphy is applied extensively in the development and evaluation of pharmaceutical drug delivery systems. It is used particularly for monitoring formulations in the gastrointestinal and respiratory tracts. The radiolabelling is generally achieved by the incorporation of an appropriate technetium-99m or indium-111 labelled radiopharmaceutical into the formulation. In the case of complex dosage forms, such as enteric-coated tablets, labelling is best undertaken by the addition of a non-radioactive tracer such as samarium-152 oxide or erbium-170 oxide followed by neutron activation of the final product. Systems investigated include tablets and multiparticulates for oral administration, enemas and suppositories, metered dose inhalers and nebulisers, and nasal sprays and drops. Gamma-scintigraphy provides information on the deposition, dispersion and movement of the formulation. The combination of such studies with the assay of drug levels in blood or urine specimens, pharmacoscintigraphy, provides information concerning the sites of drug release and absorption. Data acquired from the scintigraphic evaluation of pharmaceutical dosage forms are now being used increasingly at all stages of product development, from the assessment of prototype delivery systems to supporting the product licence application.

Diltiazem↗
PubMed1992

Antigenic variation of the bovine ephemeral fever virus glycoprotein.

Glycoprotein-specific monoclonal antibodies (MAbs) were used to select escape mutants of bovine ephemeral fever (BEF) virus to determine the escape frequency for different epitopes and to construct an epitope map. At least six antigenic sites were detected by this method and escape frequencies between 10(-2) and 10(-8) were recorded. One new non-conformational site was defined by a MAb, 5A5, which neutralized Berrimah and Kimberley viruses as well as three BEF virus strains. Batch to batch variation was detected in the BB7721 strain of BEF virus when tested for MAb neutralization. Eighteen strains of BEF virus, isolated from blood and insects from a variety of locations in Australia over a period of 33 years, were examined using MAbs and at least one epitope could not be detected in strains isolated since 1975. Implications for vaccine development are discussed.

Aedes↗
PubMed1992

Gastrointestinal transit and systemic absorption of captopril from a pulsed-release formulation.

Captopril has been administered to eight healthy male subjects by means of a pulsatile delivery system that was designed to release the drug in the colonic region of the intestine. The gastrointestinal transit and pulsatile release were followed using gamma scintigraphy. A pulsatile capsule system with release after a nominal 5-hr period was found to perform reproducibly in vitro and in vivo. In six of the eight subjects, the drug was delivered to the colon, and in the remaining two subjects, to the terminal ileum. Measurable blood levels of free captopril were found in three subjects. Variable instability of the drug in the distal intestine is suggested as a possible reason for the lack of absorption of the drug in the majority of subjects.

Adult↗
PubMed1992

In vivo evaluation of enteric-coated naproxen tablets using gamma scintigraphy.

Seven healthy, male volunteers were entered into a randomized, open crossover study of the gastrointestinal transit of two enteric-coated 500-mg naproxen tablets. Two radiolabeled tablets were given to each volunteer on two occasions separated by 7 days, once in the fasted state and once after breakfast. Radiolabeling of tablets was achieved by the incorporation of samarium-152 oxide during manufacture, followed by neutron activation of the tablet to produce the gamma-emitting isotope samarium-153. No loss of tablet integrity was seen in the stomach and all tablets disintegrated in the small intestine. Onset of tablet disintegration was controlled predominantly by gastric emptying. Time in the small intestine prior to tablet disintegration was independent of food intake. Naproxen blood levels with time were consistent with the delayed release of naproxen from the tablets. Overall, transit, disintegration, and absorption were as expected from an enteric-coated tablet.

Adult↗
PubMed1992

Epi-fluorescence microscopy and image analysis used to measure diffusion coefficients in gel systems.

A method using epi-fluorescence microscopy and image analysis has been developed to follow and quantify the diffusion of fluorescent compounds through gels. Two mathematical approaches were employed to calculate diffusion coefficients. The spatial resolution provided by the fluorescence microscope allowed diffusion to be followed over very short distances; accordingly diffusion coefficients were obtained within minutes, even for slowly diffusing systems. The method was successfully applied to the diffusion of macromolecules into agar, carbopol and mucus gel systems.

Algorithms↗
PubMed1992

Di-iodo-L-tyrosine-labelled dextrans as molecular size markers of nasal absorption in the rat.

A series of fractionated di-iodo-L-tyrosine-labelled dextrans (DIT dextrans), with a narrow range of number average molecular weights from 1260 to 45,500 Da, was administered intranasally and intravenously to anaesthetized rats. The nasal absorption of these compounds ranged from 0.6 to 52.7%. There was an inverse relationship between molecular size and the proportion of an intranasal dose absorbed. The study demonstrated the usefulness of DIT dextrans as molecular weight markers and confirmed the relationship between molecular size and nasal absorption for highly water soluble compounds. These results also supported the proposition that there is a continuous range of aqueous pores in the nasal mucosa.

Administration, Intranasal↗
PubMed1992

Intranasal insulin. Clinical pharmacokinetics.

Insulin administered nasally has considerable potential for the treatment of both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes. For patients with NIDDM it is possible to prevent preprandial hyperglycaemia and postprandial hypoglycaemia by employing a suitable and properly timed intranasal insulin dose. The low bioavailability of simple formulations of insulin can be greatly improved by using absorption enhancers or novel delivery systems such as bioadhesive microspheres. The need for nontoxic and nonirritant systems is stressed.

Absorption↗
PubMed1992

Enhanced secretory IgA and systemic IgG antibody responses after oral immunization with biodegradable microparticles containing antigen.

Intragastric immunization may lead to the induction of antibodies in the secretory immune system including saliva. The antibody response is usually short-lived. The objectives of this study were to see whether oral immunization with biodegradable microparticles containing antigen might lead to enhanced mucosal responses. Ovalbumin (OVA) was entrapped in a novel antigen delivery system comprising poly (D,L-lactide-co-glycolide) (PLGA) microparticles. Salivary IgA and serum IgG responses after three daily oral immunizations in BALB/c mice were assayed by ELISA at weekly intervals and compared with those to soluble antigen. Low levels of salivary IgA antibodies were detected at Weeks 2 and 3 in both groups and no significant differences were found. After a secondary series of intragastric immunizations at Week 4, marked differences were apparent between the groups. The mean salivary IgA titre at Week 6 was 959 +/- 494 U compared with 30 +/- 5 in the soluble OVA group (P less than 0.0001). Significant differences were still apparent at Weeks 7-8 through the value was falling. Serum IgG antibodies were detectable and were significantly greater in the particle group (at Weeks 4 and 8) than in controls (P less than 0.001). These results suggest that microparticles are taken up by antigen-presenting cells in Peyer's patches, then slowly degrade in vivo and release entrapped antigens, and thus can function as potent antigen delivery systems giving rise to both mucosal and systemic responses. Microparticles have considerable potential as a controlled released antigen delivery system for the induction of longer-term immune responses at mucosal surfaces.

Administration, Oral↗
PubMed1991

Non-phagocytic uptake of intravenously injected microspheres in rat spleen: influence of particle size and hydrophilic coating.

A recent development in prolonging the circulation time of drug carriers, such as liposomes and microspheres, has been to minimize their removal by macrophages of the reticuloendothelial system by covering their surface with hydrophilic polymers such as poloxamers, poloxamines and poly(ethyleneglycols). Here we demonstrate that this strategy may not necessarily prolong the circulatory half-life of drug carriers in all animal models. In rats, as opposed to rabbits, a non-phagocytic mechanism in the spleen may be triggered to remove efficiently from the blood drug carriers coated with hydrophilic coatings. Both the size of particle and its hydrophilic coating may act synergistically to trigger this non-phagocytic mechanism. In rats, a remarkable log to log relationship between particle size and spleen uptake was observed for both uncoated and polymeric coated microspheres. The potential implication of these observations in site-specific delivery of drug carriers is discussed.

Animals↗