Ulf Schröder

A general method for the immobilization of cells with preserved viability

SummaryMicrobial, algal, plant and animal cells have been immobilized, with preserved viability, by entrapment in various matrices according to a new bead polymerization technique. The cell polymer/monomer mixture is kept suspended in a hydrophobic phase such as soy, paraffin, or silicon oil, tri-n-butylphosphate, or dibutyphtalate, which is compatible with the cells. The various monomers or polymers tested include agarose, agar, carrageenan, alginate, fibrin, and polyacrylamide. Furthermore, by adjustment of the stirring speed of the suspension, beads of desired diameter can easily be obtained. The entrapped cells are fully viable and biosynthetically active.

Preparation and application of magnetic polymers for targeting of drugs.

There hds been constderable interest during the last few years m the area of drug targeting as it has become clear that m order to achieve optimal condrtrons for the action of pharmacologtcdl agents mteraction with non-target sites should be mmunrzed [ l] Investrgdtrons to complex antrtumour drugs with antibodies are noteworthy m this context [2] Smularly, the use of hposomes as carrters deserves mention as they are predommantly transported mto the liver and spleen [ 1 ] While studying the use of magnetic carriers in affimty chromatography [3] rt occurred to us that magnetrc material might dlso be used as support for drugs which could be brought to the target site wrth the aid of a magnetic field [4] Apart from mmlmrzmg mteractrons with non-target sites such a specific location would allow a high concentration of the drug to be used and would extend the time of exposure at the site In the followmg we wash to report on the preparation and apphcatron of such mdgnetrc drug-carrying materials

Crystallized carbohydrate spheres as a slow release matrix for biologically active substances

Described is a novel method of fabrication of crystallized carbohydrate spheres with entrapped substances where it is shown that entrapped peptide hormones such as insulin and interferon, enzymes such as plasmin and beta-galactosidase and monoclonal antibodies retain their biological activity after release from the matrix. In vitro slow release of proteins over several weeks is achieved by erosion of the matrix consisting of carbohydrate polymers such as dextran, dextrins or low molecular weight carbohydrates such as glucose and maltose, all well known biodegradable and biocompatible matrix materials.

Crystallized dextran nanospheres with entrapped antigen and their use as adjuvants

A novel and simple method is described of preparing a matrix with entrapped antigen, the matrix consisting of well characterized carbohydrates with low toxicity, i.e., dextran and starch, stabilized by crystallization. The crystallized carbohydrate spheres produced probably derive their adjuvant effect from slow antigen release and macrophage stimulation. Five months after a single injection of 80 micrograms ovalbumin entrapped in dextran spheres, mice produced antibodies against ovalbumin and this response could be enhanced further by co-entrapment of immunomodulators such as DEAE- or SO4-dextrans into the spheres. A single injection of 8 micrograms entrapped bee venom into mice gave the same IgG antibody response as 2 X 80 micrograms bee venom dissolved in water. By the same method it was possible to inject 4 times the LD50 dose of entrapped bee venom in mice without any significant side reactions.

Magnetic carbohydrate nanoparticles for affinity cell separation.

Magnetically responsive nanoparticles were prepared from enzymatically hydrolysed starch and magnetite. Two different monoclonal antibodies were covalently coupled to the particles. The antibody-coupled particles were in the size range of 100-300 nm and had an iron content of about 60%. Using 100 micrograms of magnetic particles (coupled with monoclonal mouse anti-rat Ig kappa light chain antibody) a very high depletion of surface Ig positive cells (mostly B-cells) from one million rat peripheral blood mononuclear cells could be achieved. The separation efficiency was evaluated by flow cytofluorometric analysis. This technique permits the detection of a small number of surface Ig positive cells among 10,000 negative cells.

Magnetic microspheres for targeting of drugs

Magnetic microspheres were prepared from starch. The microspheres could be crosslinked with various agents, and drugs could be entrapped adsorbed, or covalently coupled to the microspheres.