Microgel particles for the delivery of bioactive materials
AssigneeThe Regents of the University of California
InventorsJean M. J. Frechet, Niren Murthy
Life of this patent
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Abstract
Novel microgels, microparticles and related polymeric materials capable of delivering bioactive materials to cells for use as vaccines or therapeutic agents. The materials are made using a crosslinker molecule that contains a linkage cleavable under mild acidic conditions. The crosslinker molecule is exemplified by a bisacryloyl acetal crosslinker. The new materials have the common characteristic of being able to degrade by acid hydrolysis under conditions commonly found within the endosomal or lysosomal compartments of cells thereby releasing their payload within the cell. The materials can also be used for the delivery of therapeutics to the acidic regions of tumors and sites of inflammation.
Claims22
A method of delivering to a cellular compartment in an interior of a cell of an organism a bioactive material that stimulates an immune response in the cell in the organism, comprising:
- introducing to the cell a microgel composition, the microgel composition comprising:
- (a) a polymer having a bisacryloyl acetal crosslinker said bisacryloyl acetal crosslinker being essentially non-hydrolyzable above pH 7, but hydrolyzable below pH 6, wherein said bisacryloyl acetal crosslinker has the formula R2CH(OR1)2,
- wherein R1 is an acryloyl group;
- and R2 is Ar-X where
- (i) X is a water solubilizing group selected from hydrogen, methoxy, —O—(CH2—CH2—O)n—CH3 wherein n is from 1 to 10, —), —O—CH2—CH2—O—C(O)—O—Ph—NO2 and O—CH2—CH2—CH2—NH—CO- (dextran polysaccharide), wherein the dextran polysaccharide having a molecular weight from 300 to 100,000 daltons;
- and
- (ii) Ar is an aryl group and wherein said crosslinker hydrolyzes at pH 4.5 to pH 7.4;
- wherein said polymer has a particle size between 0.1-10 microns and cross linkages between 1 and 20 mole percent, and
- (b) the bioactive material, wherein said bioactive material is selected from peptides, proteins, DNA, RNA, antibodies, and interleukins;
- effecting hydrolysis of the polymer within the cellular compartment of the cell, wherein the compartment is acidic, and cleaving said crosslinker, thereby
- releasing said bioactive material into the interior of the cell.
A method of vaccination of an organism, comprising:
- introducing to a cell in the organism an acid degradable crosslinked microgel composition, the composition comprising:
- a polymer backbone selected from an acrylic polymer and a dextran polysaccharide crosslinked by an acid hydrolyzable crosslinker, wherein said crosslinker hydrolyzes at pH 4.5 to pH 7.4;
- the crosslinker having the formula R2CH(OR1)2, wherein R1 is an acryloyl group;
- and R2 is Ar-X where X is a water solubilizing group selected from hydrogen, methoxy, —O—(CH2—CH2—O)n—CH3 wherein n is from 1 to 10, —O—CH2—CH2—O—C(O)—O-Ph-NO2 and —O—CH2—CH2—CH2—NH—CO-dextran polysaccharide, having a molecular weight from 300 to 100,000 daltons;
- and Ar is an aryl group;
- a particle size of the microgel composition between 0.1-10 microns;
- cross linkages between 1 and 20 mole percent;
- and a bioactive material capable of effecting vaccination of the organism,
- cleaving said crosslinker by hydrolysis, and
- releasing said bioactive material in the cell, wherein said bioactive material is selected from the group consisting of peptides, proteins, polynucleotides, DNA, RNA, antibodies, interleukins, and vaccines, and effects vaccination of the organism.
Dependencies are inferred from the claim text.