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Biomedical subjects

L Illum

Publications and source records attributed to L Illum.

At least 91 records · Page 5Linked to original sources
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

Human serum albumin as a probe for surface conditioning (opsonization) of block copolymer-coated microspheres.

The adsorption of human serum albumin to polystyrene microspheres sterically stabilized with block copolymers, was investigated using photon correlation spectroscopy and laser doppler anenometry. The block copolymers used were non-ionic surfactants of the poloxamer and poloxamine series made of polyoxyethylene and polyoxypropylene chains. Photon correlation spectroscopy and laser doppler anenometry showed that the coating reduced the adsorption of the protein to the polystyrene microspheres surface. Quantitative studies using 125I-labelled human serum albumin and sodium dodecyl sulphate-polyacrylamide gels (in combination with densitometry), were employed to evaluate the adsorption of human serum albumin to uncoated and coated polystyrene microspheres. They confirmed that the hydrophilic polyoxyethylene steric layer, created by coating with the block copolymers, reduced the adsorption of human serum albumin. Moreover, the amount of human serum albumin adsorbed was related to the polyoxyethylene content of the block copolymers.

Absorption↗
PubMed1992

Vaginal absorption of insulin in the rat: effect of penetration enhancers on insulin uptake and mucosal histology.

The absorption of insulin across the vaginal mucosa into the systemic circulation was studied in ovariectomized rats given subsequent estrogen treatment. Blood glucose levels were determined as an indirect measure of insulin absorption, and the effect of various enhancers on the hypoglycemic response was investigated. In the absence of any enhancer, no decrease in blood glucose levels was observed after vaginal administration of insulin. However, the coadministration of sodium taurodihydrofusidate, polyoxyethylene-9-lauryl ether, lysophosphatidylcholine, palmitoylcarnitine chloride, and lysophosphatidylglycerol significantly increased hypoglycemia, whereas citric acid had little effect. The histological changes in the vaginal epithelium after treatment with the enhancer systems were variable and often severe. While the efficacy of these compounds in promoting the vaginal absorption of insulin is encouraging, their mechanisms of action and long-term histological effects are yet to be defined.

Absorption↗
PubMed1992

Vaginal immunization of rats with a synthetic peptide from human immunodeficiency virus envelope glycoprotein.

Local secretory immunity in the vagina may confer a degree of protection against heterosexual transmission of human immunodeficiency virus (HIV). Since the vagina has been shown to respond to local immunization, we have undertaken intravaginal immunization of rats with a 20-mer peptide (amino acid residues 102 to 121) of the HIV-1 envelope glycoprotein (gp120). The peptide was administered in combination with an 'absorption enhancer', lysophosphatidyl glycerol (LPG), which has previously been shown to promote the absorption of intravaginally administered peptides, while exerting only mild effects on epithelial membrane integrity. Intravaginal immunization with LPG and the peptide induced serum and vaginal wash IgA and IgG antibody responses which were enhanced in comparison to those after immunization with the peptide alone. Serum antibodies induced by both subcutaneous and intravaginal immunization were able to recognize recombinant HIV-1 gp120. However, the rat antiserum displayed no neutralizing activity against the virus. These results demonstrate that LPG is an effective immunological adjuvant for intravaginally administered peptide antigens. An alternative absorption enhancer, bestatin (BES), was not effective as an immunological adjuvant when administered intravaginally and blocked the adjuvant activity of LPG when BES and LPG were used in combination.

AIDS Vaccines↗
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↗
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↗
PubMed1991

The nasal delivery of peptides and proteins.

Many drugs of the future will be therapeutically active peptides and proteins developed through recombinant-DNA technology. A major factor limiting their exploitation is the current lack of appropriate non-parenteral delivery systems. Nasal systems incorporating absorption enhancers may provide a convenient, efficient means of administering protein and peptide therapeutics.

Administration, Intranasal↗
PubMed1991

Drug delivery.

Methods for the delivery of the products of biotechnology, namely peptides and proteins, are reviewed. More efficient methods of parenteral administration include the incorporation of drugs in liposomes, whereas the system favoured for respiratory delivery is the nasal route. The improved oral delivery of polypeptides remains an elusive goal.

Animals↗
PubMed1990

The effect of infused fat emulsions on reticuloendothelial function in the rabbit.

The effect of the infusion of different fat emulsions (Intralipid and MCT/LCT mixtures) on the reticuloendothelial function of the rabbit has been investigated. Emulsions containing 20% dispersed triglyceride were administered over 6 h to a total of 3 g/kg body weight. The extent of blockade of the reticuloendothelial system was measured using a labelled probe in the form of technetium-99m labelled albumin microspheres. Scintigraphic and blood and organ level determinations demonstrated that all emulsions caused an impairment of reticuloendoethlial function, but this was small.

Journal Article↗
PubMed1990

Nasal absorption enhancers for biosynthetic human growth hormone in rats.

The effects of several prospective absorption enhancers were assessed on the nasal absorption of biosynthetic human growth hormone (hGH) in the rat. These enhancers function by alternative mechanisms that include enzyme inhibition, reduction in mucus viscosity, and enhancement of membrane fluidity. The levels of plasma hGH achieved were determined by an enzyme-linked immunosorbent assay. The increase in peak height was calculated relative to nasal administration of hGH alone without any enhancers and the relative bioavailability was calculated with reference to subcutaneous injection data. A lysophospholipid, lysophosphatidylcholine, gave the highest peak concentration, with an increase in peak height of 450% and a relative bioavailability of 25.8%. However, the greatest increase in AUC (291%) was achieved with the aminopeptidase inhibitor, amastatin, which gave a relative bioavailability of 28.9%. A mucolytic agent, N-acetyl-L-cysteine, and a transmembrane fatty acid transporter, palmitoyl-DL-carnitine, were also found to promote the nasal absorption of hGH in this model, with relative bioavailabilities of 12.2 and 22.1%, respectively. Bestatin, an enzyme inhibitor, was not an effective absorption enhancer for hGH in this model.

Absorption↗
PubMed1990

Physiopathological and physicochemical considerations in targeting of colloids and drug carriers to the bone marrow.

The ability of the bone marrow to remove particulate matters from the circulation, opens up perhaps an opportunity for the delivery of therapeutic agents by means of colloidal drug carrier systems such as liposomes, emulsions, nanoparticles, etc. for the treatment of diseases and disorders of this multifunctional organ of the body. This article is designed to provide a critical review on fundamentals, problems, current progress, and future prospects of site-specific delivery of intravenously injected colloidal drug carriers to the bone marrow.

Animals↗
PubMed1990

Absorption of peptides and proteins from the respiratory tract and the potential for development of locally administered vaccine.

Since the appearance of the first therapeutic active peptides and proteins produced by genetic engineering, there has been an ever-increasing demand to be able to deliver these drugs by routes other than the parenteral. For most drugs the need for alternative delivery systems is due to short-half lives in the bloodstream, large extents of first pass metabolism, or the possibility of obtaining endogenous-like plasma profiles. A wide variety of drugs have now been tested for bioavailability after respiratory, especially intranasal, administration. A small range of drugs (such as propranolol and progesterone) appears to be absorbed effectively via the nasal route and shows bioavailabilities comparable to the intravenous route. However, most drugs shows a much lower degree of absorption. The present review discusses the critical steps that have to be considered when attempting to deliver drugs effectively via the nasal and pulmonary routes and how it is possible by suitable formulation of delivery systems to overcome some of the most important barriers to drug absorption. Furthermore, the immunological responses to respiratory absorption of exogenous peptides and proteins and the potential for development of locally administered vaccines are reviewed.

Absorption↗
PubMed1988

Polymeric microspheres as drug carriers.

The use of polymeric microsphere systems (including polypeptides) as vehicles for delivering drugs by a variety of routes is considered with particular reference to parenteral administration. Microsphere formulation is discussed with emphasis on the role of surface properties and how these can determine the fate of administered particles. Studies on the use of adsorbed block copolymers that can alter processes of protein uptake onto particle surfaces (opsonization) as well as the interaction of particles with macrophages (cell-particle adhesion) are described. Data are presented which show that by the selection of the appropriate coating material it is possible to direct particles within the body to sites such as the lung, liver, bone marrow, or to retain materials within the systemic circulation.

Adsorption↗
PubMed1987

Targeting of colloidal particles to the bone marrow.

Since intravenously administered colloidal particles are normally removed efficiently by the reticuloendothelial cells of the liver and spleen only a small fraction of these particles will reach the bone marrow. By coating model microspheres with a block co-polymer (poloxamer 407) it has been possible effectively to hinder the liver/spleen uptake and obtain a deposition of the microspheres primarily in the bone marrow. Such a carrier system will have application in radiodiagnosis and for treatment of various diseases in the bone marrow.

Animals↗