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Biomedical subjects

L Illum

Publications and source records attributed to L Illum.

106 records · Page 6Linked to original sources
PubMed1987

The organ distribution and circulation time of intravenously injected colloidal carriers sterically stabilized with a block copolymer--poloxamine 908.

Colloidal carriers injected intravenously are normally removed rapidly and efficiently by the liver and this represents a major barrier to drug targeting. By coating model microspheres and emulsions with a block co-polymer (poloxamine) it has been possible to keep the carrier circulating in the vascular compartment with little or no uptake by the reticuloendothelial system.

Animals↗
PubMed1987

Surface characteristics and the interaction of colloidal particles with mouse peritoneal macrophages.

The effect of surface characteristics on the interaction of sterically stabilized polystyrene particles with mouse peritoneal macrophages was studied using a range of poloxamers and poloxamine as coating agents. The coated particles were characterized in terms of thickness of coating layer, surface charge and critical flocculation temperature. The relative phagocytic uptake was found to decrease with increasing adsorbed layer thickness i.e. longer hydrophilic polymer chains of the coating agent and consequently a greater steric stabilization effect.

Animals↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1984

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↗
PubMedDate not supplied

Sustained release chitosan microspheres prepared by novel spray drying methods.

Modified spray drying methods, especially a novel w/o/w emulsion-spray drying method, were developed to prepare chitosan microspheres with a sustained drug release pattern. Release of the model drugs cimetidine and famotidine, from the microspheres prepared by the emulsion-spray drying methods, was greatly retarded with release lasting for several hours, compared with drug loaded microspheres prepared by conventional-spray drying or emulsion methods where drug release was almost instant. The slow release of drug was partly due to the poor wetting ability of the microspheres which floated on the surface of the dissolution medium. The addition of a wetting agent increased the release rate significantly. The coating of the microspheres with gelatin decreased the rate of release of drug in the presence of wetting agents.

Aerosols↗
PubMedDate not supplied

Differences in the adsorption behaviour of poly(ethylene oxide) copolymers onto model polystyrene nanoparticles assessed by isothermal titration microcalorimetry correspond to the biological differences.

The adsorption behaviour of a tetrafunctional copolymer of poly (ethylene oxide)-poly (propylene oxide) ethylene diamine (commercially available as Poloxamine 908) and a diblock copolymer of poly (lactic acid)-poly (ethylene oxide) (PLA/PEG 2:5) onto a model colloidal drug carrier (156 nm sized polystyrene latex) is described. The adsorption isotherm, hydrodynamic thickness of the adsorbed layers and enthalpy of the adsorption were assessed. The close similarity in the conformation of the poly (ethylene oxide) (PEO) chains (molecular weight 5,000 Da) in the adsorbed layers of these two copolymers was demonstrated by combining the adsorption data with the adsorbed layer thickness data. In contrast, the results from isothermal titration microcalorimetry indicated a distinct difference in the interaction of the copolymers with the polystyrene colloid surface. Poloxamine 908 adsorption to polystyrene nanoparticles is dominated by an endothermic heat effect, whereas, PLA/PEG 2:5 adsorption is entirely an exothermic process. This difference in adsorption behaviour could provide an explanation for differences in the biodistribution of Poloxamine 908 and PLA/PEG 2:5 coated polystyrene nanoparticles observed in previous studies. A comparison with the interaction enthalpy for several other PEO-containing copolymers onto the same polystyrene colloid was made. The results demonstrate the importance of the nature of the anchoring moiety on the interaction of the adsorbing copolymer with the colloid surface. An endothermic contribution is found when an adsorbing molecule contains a poly (propylene oxide) (PPO) moiety (e.g. Poloxamine 908), whilst the adsorption is exothermic (i.e. enthalpy driven) for PEO copolymers with polylactide (PLA/PEG 2:5) or alkyl moieties.

Adsorption↗
PubMedDate not supplied

Egg albumin microspheres containing paracetamol for oral administration. I. In vitro characterization.

Different egg albumin microsphere systems for oral administration of paracetamol were prepared by the emulsion and capillary extrusion methods. The size of the microspheres depended on the method used to produce the microcapsules and also the size of the crystals of paracetamol. The effect of the following factors on in vitro dissolution were studied: different denaturation processes, variation in the ratio of paracetamol to albumin, size of microspheres, remnant oil in the microspheres, and the coating of the microspheres with membranes of polymethacrylates (Eudragit). The most important factors to control the release of paracetamol from the microspheres were the denaturation process and the use of waxes and membranes to delay the release of paracetamol from the microspheres. The egg albumin microspheres were very porous and permeable to water and thus the release of the paracetamol from the matrix was usually fast unless the microspheres were suitably coated, with, for example, Eudragit RL or RS.

Acetaminophen↗
PubMedDate not supplied

Egg albumin microspheres containing paracetamol for oral administration. II. In vivo investigation.

Egg albumin microspheres containing paracetamol for oral administration were prepared and their in vivo characteristics evaluated. The egg albumin microspheres were able to improve the organoleptic characteristics of paracetamol formulations. The pharmacokinetic characteristics of three different formulations of paracetamol were evaluated in six volunteers. The formulations administered orally were: (1) Paracetamol granulated with lactose (reference), (2) Egg albumin microspheres and (3) Egg albumin microspheres coated with polymethacrylate. The pharmacokinetic characteristics for formulations 1 and 2 were similar but formulation 3 gave significant differences (p less than 0.05) in Ka, Cmax and tmax. No significant differences in relative bioavailability were observed.

Acetaminophen↗
PubMedDate not supplied

Preparation of human serum albumin microspheres by a novel acetone-heat denaturation method.

Human serum albumin (HSA) microspheres have been produced in the size range of 200 nm to 10 microns by the controlled addition of acetone to an aqueous solution of HSA, followed by stabilization of the formed microspheres at an elevated temperature. Microspheres produced by this acetone-heat denaturation method could be stabilized at relatively low temperatures (75 degrees C) over a short time period (15-30 min). The acetone-heat denaturation method is different from the traditional oil/water technique for preparation of HSA microspheres, both in terms of production method and the avoidance of high temperatures (> 100 degrees C) and extended heating times (> 30 min) for stabilization. This paper describes the influence of process conditions, such as volumes of acetone and HSA concentration, on the formation of the microspheres and their morphological characteristics. A loading efficiency of 8 per cent was achieved for the HSA microspheres when using rose bengal as a model compound. The release of rose bengal from the microspheres in phosphate buffered saline at 37 degrees C was dependent on the presence of the surfactant Tween 80, and varied from a 5 per cent release in 14 days in the absence of surfactant to a 50 per cent release in 8 h in the presence of surfactant.

Acetone↗