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Biomedical subjects

J Kreuter

Publications and source records attributed to J Kreuter.

At least 19 recordsLinked to original sources
PubMed1995

Nanoparticles as adjuvants for vaccines.

PMMA nanoparticle adjuvants can be manufactured in a physicochemically reproducible manner. Their particle size can be controlled within narrow limits. Immunogens may be either incorporated or adsorbed to these nanoparticles. PMMA nanoparticles induced significantly higher and more prolonged antibody responses against a variety of immunogens, including influenza virions and subunit vaccines, BSA, and HIV-1 and HIV-2 split vaccines. In addition, a protective immune response against challenge with live influenza virus was induced and a better stability of the immunogen was observed after incorporation or adsorption of influenza virions or subunits to PMMA nanoparticles. The observation that PMMA did not induce antibodies against gp120 contained in the HIV-2 split vaccine demonstrates that different adjuvants or carriers may be required for different antigens. A combination of two or more different adjuvants or carriers may be necessary to induce the optimal immune response against antigen mixtures as present in most vaccine preparations. PMMA seems to be a safe adjuvant material. It is very slowly biodegradable and has been used in surgery in humans for over 40 years, and now warrants continued investigation as a vaccine adjuvant.

Adjuvants, Immunologic↗
PubMed1992

Drug and vehicle deposition from topical applications: use of in vitro mass balance technique with minoxidil solutions.

The disposition of minoxidil and propylene glycol from topical solutions was measured by using an in vitro mass balance technique. The experimental approach included assessment of the following compartments of the skin and the diffusion cell as a function of time: (1) donor compartment; (2) hairless mouse skin surface, epidermis, and dermis; and (3) receiver compartment. Excellent mass balance was achieved for minoxidil at three doses. However, the recovery of propylene glycol depended on both application volume and time. The experiment involving the evaporation of propylene glycol and water from the propylene glycol:ethanol:water (20:60:20, v/v) mixture, which was placed in the well of a tissue culture plate at room temperature and 37 degrees C, substantiated the loss of vehicles to the air. When a thin application of 20 microL/cm2 was used, 60% of the propylene glycol was unaccounted for after 16 h. The evaporation of propylene glycol concentrated the solution to supersaturation, precipitated out the drug, and then stabilized the thermodynamic activity of the drug in the vehicle. The amount of formulation applied influences the rate of concentration and, thus, the time at which minoxidil precipitates. The precipitation limits the amount of minoxidil that can be absorbed and leads to poor percutaneous absorption of drug from the formulation.

Administration, Topical↗
PubMed1992

Phagocytosis of nanoparticles by human immunodeficiency virus (HIV)-infected macrophages: a possibility for antiviral drug targeting.

Human monocytes/macrophages (MO/MAC) were isolated from peripheral blood and cultivated on hydrophobic Teflon membranes. This culture system is suitable for HIV infection of MO/MAC in vitro. After transfer into 24-well plates the mature macrophages (infected or uninfected) were used for measurements of phagocytosis. The uptake of different, radioactively labeled nanoparticles (NP) made of polyalkylcyanoacrylate, polymethylmethacrylate (PMMA), and human serum albumin (HSA) by the macrophages was determined. In addition, the influence on phagocytosis of size and composition, concentration, and surface of the NP was studied. Further, macrophages of different state of activation were tested. NP made of polyhexylcyanoacrylate (PHCA) or human serum albumin with a diameter of about 200 nm were found most useful for targeting antiviral substances such as azidotymidine to macrophages. Cells infected in vitro with HIV-1D117/III, a monocytotropic HIV isolate from a perinatally infected child, possessed an even higher phagocytotic activity than noninfected cells. Macrophages isolated from HIV-infected patients also showed good incorporation of NP. Thus, the concept of a specific targeting of antiviral substances to macrophages in HIV-infected individuals appears quite promising.

Antiviral Agents↗
PubMed1992

Lymphatic targeting of polymeric nanoparticles after intraperitoneal administration in rats.

Following intraperitoneal administration, the lymphatic targeting of polyacrylic nanoparticles has been evaluated in thoracic duct cannulated rats. The dosage forms administered consisted of carbon-14 polyhexylcyanoacrylate nanoparticles (PHCA) and polymethylmethacrylate (PMMA) nanoparticles. The carbon-14 concentrations were much higher in the excreted thoracic lymph than in the blood for both types of particles. The most dramatic results were found in the mediastinal nodes since the carbon-14 concentrations of rats receiving PHCA and PMMA nanoparticles by the ip route were 70- to more than 2000-fold higher than in the corresponding nodes of animals treated by the intravenous route. This potential lymphatic targeting could prove valuable in cancerology to treat tumors that metastasize in the peritoneal cavity or via lymphatic pathways such as colon carcinomas.

Animals↗
PubMed1991

Liposomes and nanoparticles as vehicles for antibiotics.

Colloidal drug carriers such as liposomes and nanoparticles are easily taken up by phagocytic cells and accumulate in the organs of the reticuloendothelial system. Therefore, they hold promise as carriers for the treatment of intracellular infections with antibiotics that would normally not find easy access to intracellular sites. Consequently, in in vitro and in vivo experiments the therapeutic efficacy of substances such as amphotericin B, dihydrostreptomycin, amikacin, ampicillin, stibogluconate against a number of microorganisms including Leishmania donovani, Candida albicans, Staphylococcus aureus, Mycobacterium avium, Listeria monocytogenes, and Salmonella typhimurium was increased significantly by binding to liposomes and nanoparticles.

Animals↗
PubMed1991

High antibody titres in mice with polymethylmethacrylate nanoparticles as adjuvant for HIV vaccines.

The aim of the present study was to determine the effect of polymethylmethacrylate (PMMA) nanoparticles as adjuvants for an HIV-2 whole-virus vaccine in mice. The data clearly revealed that PMMA nanoparticles induced 10-100-fold higher antibody titres than aluminium hydroxide or an aqueous vaccine control preparation as measured by enzyme-linked immunosorbent assay. Moreover, the high antibody titres obtained with PMMA as adjuvant appeared to be stable for between 10 and 20 weeks after immunization. In contrast, the titres of the control preparations, fluid or aluminium hydroxide formulations, decreased after 10 weeks.

Adjuvants, Immunologic↗
PubMed1991

Use of liposomes, viral capsids, and nanoparticles as DNA carriers.

We tested a variety of liposomes for parameters such as DNA binding capacity and DNase I protection of incorporated and attached DNA to elucidate their use as vehicles for DNA transfer into cells and animals. The results were compared to other potential DNA vehicles, empty viral capsids, and nanoparticles. Maximal binding capacity was achieved for positively charged nanoparticles, DNase I protection was observed for most preparations with neosome preparations being least efficient. The uptake of radiolabeled DNA by cells in culture was determined for cationic and nonionic surfactant vesicles, viral capsids, and nanoparticles. Cellular DNA uptake was best for dioleoyl-derived positively charged liposomes (N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride; DOTMA) and the DNA could be shown to be physiologically active. The recombination rate for DNA fragments transfected in polyoma capsids in live mice was higher than for liposome mediated transfection. Homologous recombination could be observed for both DOTMA and polyoma-mediated DNA transfer.

Animals↗
PubMed1989

Comparison of different models for the testing of pilocarpine eyedrops using conventional eyedrops and a novel depot formulation (nanoparticles).

An objective in the development of ophthalmic formulations is the use of in vitro or animal models that closely resemble the clinical situation. For this reason, experiments with conventional pilocarpine nitrate eyedrops and a depot formulation of pilocarpine nitrate sorbed to poly (butylcyanoacrylate) nanoparticles were carried out. In vitro, the diffusion of pilocarpine through bovine cornea was measured using Edelhauser cells. In vivo, the rabbit aqueous humor concentration of pilocarpine and miosis were determined after application of the above formulations. In addition, intraocular pressure was measured. Since pilocarpine has little influence on intraocular pressure in healthy rabbits, the pressure had to be increased artificially. Three models were employed that are described in the literature, namely, the betamethasone model, the alpha-chymotrypsin model, and the water-loading model. Pilocarpine could be loaded onto nanoparticles by 15% but was rapidly released from the nanoparticles based on the bovine corneal experiment. Nanoparticles only enhanced the aqueous humor concentration at 30 min; this increase, however, led to a considerably extended period of miosis as well as a reduction in intraocular pressure. The duration of the action and the intensity of the response were different among the three models tested. According to the present results, the betamethasone model seems to represent the best correlation to the clinical situation.

Animals↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1984

Distribution and elimination of polymethyl methacrylate nanoparticles after peroral administration to rats.

Polymethyl [1-14C]methacrylate nanoparticles were administered orally to bile cannulated rats. Ten to fifteen percent of the administered radioactivity was absorbed and found in the bile and urine. Within 48 h, 94-97% of the absorbed radioactivity had been eliminated from the body. After 8 d, the highest residual radioactivity was found in the bone marrow, fatty renal tissue, stomach, liver, and lymph nodes.

Administration, Oral↗
PubMed1984

Distribution and elimination of coated polymethyl [2-14C]methacrylate nanoparticles after intravenous injection in rats.

Surfactant-coated polymethyl [2-14C]methacrylate nanoparticles had significantly different time-course distribution patterns in rats than noncoated and albumin-coated particles. Blood concentrations of poloxamer 188-coated particles were 70-fold higher after 30 min, and the particles persisted at higher levels in the circulation for up to 2 h. The initial and final liver levels were significantly lower (38% after 30 min, 51% after 7 d) and spleen levels were significantly higher (21% after 30 min, 23% after 7 d) than non-coated particles (74% in the liver and 5% in the spleen after 7 d) and the albumin-coated particles (84% in the liver and 5% in the spleen after 7 d). Specific activity was somewhat higher for the surfactant-coated particles in other organs such as the lungs, kidneys, testicles, ovaries, and lymph nodes. The bovine serum albumin sorption behavior of polymethyl methacrylate nanoparticles was followed under various conditions, and adsorption was found to increase with increasing protein concentration and increasing temperature, reaching a maximum at the isoelectric point of pH 4.9 after approximately 12 h of incubation. The zeta potential of the particles decreased with increasing pH, and the change was more pronounced with the albumin-coated particles.

Animals↗
PubMed1983

Distribution and elimination of poly(methyl methacrylate) nanoparticles after subcutaneous administration to rats.

Poly(methyl [1-14C]methacrylate) nanoparticles were injected subcutaneously into rats. Almost all of the radioactivity stayed at the injection site. After an initial urinary and fecal excretion of approximately 1% of the administered dose per day, the rate of elimination dropped to a low level (approximately 0.005%/day via the feces and approximately 0.0005%/day via the urine) within 70 days. After 200 days, the fecal elimination increased exponentially until a greater than 100-fold increase was observed after 287 days in one rat. After this time, a tendency for an increase in fecal elimination was also observed in the other animals, and the radioactivity in all organs and tissue increased by approximately 100 times in all animals in comparison with the organ radioactivity determinations at earlier times.

Animals↗
PubMed1983

Comparative study on the cytostatic effects and the tissue distribution of 5-fluorouracil in a free form and bound to polybutylcyanoacrylate nanoparticles in sarcoma 180-bearing mice.

The binding of 5-fluorouracil to polybutylcyanoacrylate nanoparticles yielded an enhanced efficacy against Crocker sarcoma S 180 and a higher toxicity of the drug measured by induced leukopenia, body weight loss and premature death. The efficacy was further increased by an increase in the polymer-to-drug ratio. The nanoparticles yielded a prolonged persistence of the 5-fluorouracil in all organs examined including the tumor. These particles hold promise as carriers for cytostatics, since their distribution may be favorably altered by coating them with certain proteins or surfactants or by the attachment of monoclonal antibodies.

Animals↗