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Biomedical subjects

P P Speiser

Publications and source records attributed to P P Speiser.

At least 19 recordsLinked to original sources

Nanoparticles and liposomes: a state of the art.

The loading of drugs into ultrafine host vesicles or colloidal capsules in the nanometer size range is an acknowledged technique for the optimization of controlled drug delivery. The main purpose will always be to design inert auxiliary accompanying materials; to use body-friendly and biodegradable excipients; and to miniaturize the drug carrier system dramatically in order to get good stability, excellent absorption, quantitative tissular transfer and, therefore, the expected pharmacodynamic activity. Furthermore, side effects and foreign body irritation should be avoided and a good local and systemic tolerance during and after medication should be a condition sine qua non. The actual state of the art is shown with 4 practical application examples, namely: a cellular uptake by endocytosis and a specific lysosomotropic cell transfer with cell tracer-loaded nanoparticles; the strong immunosuppressive stimulation of nanocapsules--as new adjuvants--when loaded with viral or other antigens; the better blood-brain barrier transfer of an antiparkinson drug when covalently bound to special liposomes; and the use of minivesicles for controlled site-specific anticancer drug release (tumor targeting). In the future, we must find a possibility to deliver the correct dose of the drug precisely to the diseased target organs, tissues or cells of destination, without flooding the organism with massive drug doses. One technologic answer could be the minicarrier concept with specific pathfinders and aspecific pretargeters that serve as switchmen to guide the drug-loaded carrier to the organs, with precise spot landing.

Animals↗

Distribution of polyhexylcyanoacrylate nanoparticles in nude mice over extended times and after repeated injection.

Carbon-14-labeled polyhexylcyanoacrylate nanoparticles, with diameters between 200 and 300 nm, were injected intravenously into nude mice. The distribution in liver, spleen, lung, heart, kidney, GI tract, gonads, brain, muscle, and serum was investigated by liquid scintillation counting. After a single injection, the radiolabel was cleared slowly with 45% remaining after 28 d and 8% remaining after 140 d. After repeated injection with an interval of 28 d (twice or thrice), relatively higher proportions of the dose were found in the spleen and lung as compared with those in other organs. No histological alterations were observed in the liver, spleen, or lung.

Animals↗

Influence of hydrophobicity on the adjuvant effect of particulate polymeric adjuvants.

The hydrophobicity of particulate polymeric acrylic adjuvants was altered by insertion of hydroxyl groups, exchange of a methyl group against a cyano group or elongation of the ester side chain length. These adjuvants were tested by determination of the antibody response after immunization using bovine serum albumin or by measuring the protection against infection using influenza as the antigen. In addition, the hydrophobicity was determined by measurement of the water contact angles. The adjuvant effect increased with increasing hydrophobicity.

Adjuvants, Immunologic↗

Distribution of polyhexyl cyanoacrylate nanoparticles in nude mice bearing human osteosarcoma.

[14C]Polyhexyl cyanoacrylate nanoparticles (PHCA), with diameters between 200 and 300 nm, were injected intravenously into nude mice bearing a human osteosarcoma. The distribution in liver, spleen, lung, heart, kidney, GI tract, gonads, brain, muscle, as well as in serum and transplanted tumor fragments was investigated by liquid scintillation counting. The peak levels in all organs with the exception of tumor and spleen were reached within 24 h. The highest levels were found in the organs of the reticuloendothelial system, liver, spleen, and lungs. The radioactivity in the other organs was found to be low, approximately 2%. In the tumor and the spleen the highest levels of radioactivity were found at approximately 7 d. At this stage the level of radioactivity in the tumor was 40 times higher than that in muscle. However, the amount of isotope detected in the tumor was still generally less than 1% of the injected dose. The concentration of radioactivity in the tumor was found to be quite variable. Higher levels of radioactivity were correlated with a low amount of tumor necrosis indicating the importance of viable tumor tissue for the accumulation of the radiolabel in this particular animal model.

Adult↗

Influence of the particle size on the adjuvant effect of particulate polymeric adjuvants.

The influence of the particle size of poly(methyl methacrylate) and polystyrene particles on the adjuvant effect of model vaccines was investigated in mice using bovine serum albumin as the antigen. The particle sizes of the adjuvants were between 62 and 306 nm. Smaller particles yielded a much better adjuvant effect than bigger particles. The adjuvant effect of the small polymer particles was better than that of 0.2% Al(OH)3. All adjuvants yielded a higher antibody response than the fluid antigen preparation.

Adjuvants, Immunologic↗

In vitro studies of poly(methyl methacrylate) adjuvants.

Poly(methyl methacrylate) adjuvants, prepared by polymerizing monomeric methyl methacrylate in the presence of influenza virions or by addition of the virions to previously polymerized poly(methyl methacrylate) particles, were studied by means of the hemagglutination test, antibody binding, and electron microscopy. The results indicated that the virions were coated partly when the polymerization was carried out in the presence of the virus, whereas the virions were probably adsorbed when added to polymerized particles.

Adjuvants, Immunologic↗

Polymerized micelles and their use as adjuvants in immunology.

A polymerization process is described for the preparation of hydrophilic micelles containing solubilized drug molecules in a colloidal aqueous system of dissolved monomers. A hydrocarbon medium constitutes the outer phase. After secondary solubilization with the aid of selected surfactants, polymerization of micelles under different conditions takes place. The formulation of drugs including labile proteins in the ultrafine polymer components ("nanoparts") and their isolation are possible without noticeable destruction of the encapsulated molecules. Entrapped tagged material (human 125I-immunoglobulin G) shows a stable fixation in such nanoparts during long-term in vitro liberation trials. Nanoparts are visible with the aid of an electron microscope. They are mostly spherical in shape and smaller than 80 nm in diameter. They form real colloidal aqueous solutions. Nanoparts are suitable to embed antigenic material (tetanus toxoid and human immunoglobulin G) for parenteral use. These preparations show intact biological activity and high antibody production in animals.

Adjuvants, Immunologic↗

Release of a drug from homogeneous ointments containing the drug in solution.

The rate of release of resorcinol (5%) from hydrogels (Carbopol, sodium carboxymethylcellulose, starch), lipogels (alcoholic-base, esteric-bases containing different amounts of beeswax with and without a spreading additive, respectively) and Labrafils has been examined. For the experimental design adopted the release of the drug is linear between 10 and 70% of the amount of drug released. The results agree well with the mathematical model postulated by Higuchi (1962) for the release of a drug from homogeneous ointments containing the drug in solution.

Buffers↗

New adjuvants on a polymethylmethacrylate base.

A new type of adjuvant using influenza virus as an antigen is presented. The new adjuvant was produced by polymerizing monomeric methylmethacrylate in the presence of the antigen. As a comparison, influenza virus was added to previously polymerized polymethylmethacrylate particles. In animal experiments, the antibody response in mice and guinea pigs was measured. After polymerization in the presence of the antigen, the adjuvant effect was dependent on the methylmethacrylate concentration used, reaching an optimal concentration at 0.5%. This adjuvant preparation was considerably more effective than simple addition of virus to comparable polymethacrylate preparations or to aluminum hydroxide. The latter two adjuvants were approximately equivalent in effectiveness.

Adjuvants, Immunologic↗

The use of new polymethylmethacrylate adjuvants for split influenza vaccines.

Split influenza virus vaccines with varying antigen content were adjuvated with polymethylmethacrylate particles, produced by polymerizing monomeric methylmethacrylate in the presence of the subunits, or by addition of the subunits to previously polymerized methacrylate particles. Both adjuvants yielded higher antibody titers than aluminum hydroxide or fluid vaccines. The character of the antigen-adjuvant conjugate of both types of polymer adjuvants is discussed.

Acrylic Resins↗

Nanoencapsulated fluorescence indicator molecules measuring pH and pO2 down to submicroscopical regions in the basis of the optode-principle.

To measure pO2 in gases or fluids and pH in solutions the fluorescence indicators pyrene butyric acid and beta-methylumbelliferone, respectively, were nanoencapsulated to obtain nano-probes for measurement in physiological structures of nano-range. For pH the fluorescence changes of beta-methylumbelliferone were monitored, for pO2 the fluoresence quenching of pyrene butyric acid by oxygen were registered. Drawing log (S1/S2) versus pH, one obtains a straight line between the pH from 6 to 8. A linear increase in pO2 between 0 and 400 torr yields a linear increase in the reciprocal fluorescence signal.

Butyrates↗

Sorption of 5-fluorouracil from aqueous solutions onto methyl methacrylate nanoparticles.

The sorption of 5-fluorouracil from aqueous solutions onto poly(methyl methacrylate) was investigated. Linear sorption isotherms were obtained and no crystallinity of the nanoparticles after sorption was detectable by X-ray analysis indicating a partitioning of the drug into the polymer particles-forming a solid solution. Standard enthalpy, standard entropy and standard free energy of sorption were -36.9 kJ mol-1, -85.0 J mol-1 K-1 and -12.0 kJ mol-1, respectively.

Drug Compounding↗